Adolf Pfefferbaum
Professor of Psychiatry and Behavioral Sciences, Emeritus
Academic Appointments
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Emeritus Faculty, Acad Council, Psychiatry and Behavioral Sciences
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Member, Bio-X
Current Research and Scholarly Interests
Abnormalities in brain structure and function in healthy aging, alcoholism, HIV infection, and Alzheimer's Disease; diffusion tensor imaging of white matter microstructure in alcoholism; spectroscopic analysis of brain brain metabolite concentrations in alcoholism and HIV infection; functional neuroimaging of cognitive networks in alcoholism.
All Publications
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Aging, HIV infection, and alcohol exert synergist effects on regional thalamic volumes resulting in functional impairment.
NeuroImage. Clinical
2024; 44: 103684
Abstract
OBJECTIVE: Pharmacologically-treated people living with HIV infection have near-normal life spans with more than 50% living into at-risk age for dementia and a disproportionate number relative to uninfected people engaging in unhealthy drinking. Accelerated aging in HIV occurs in some brain structures including the multinucleated thalamus. Unknown is whether aging with HIV affects thalamic nuclei and associated functions differentially and whether the common comorbidity of alcohol use disorder (AUD)+HIV accelerates aging.METHODS: This mixed cross-sectional/longitudinal design examined 216 control, 69 HIV, and 74 HIV+AUD participants, age 25-75years old at initial visit, examined 1-8 times. MRI thalamic volumetry, parcellated using THalamus Optimized Multi-Atlas Segmentation (THOMAS), identified 10 nuclei grouped into 4 functional regions for correlation with age and measures of neuropsychological, clinical, and hematological status.RESULTS: Aging in the control group was best modeled with quadratic functions in the Anterior and Ventral regions and with linear functions in the Medial and Posterior regions. Relative to controls, age-related decline was even steeper in the Anterior and Ventral regions of the HIV group and in the Anterior region of the comorbid group. Anterior volumes of each HIV group declined significantly faster after age 50 (HIV=-2.4%/year; HIV+AUD=-2.8%/year) than that of controls (-1.8%/year). Anterior and Ventral volumes were significantly smaller in the HIV+AUD than HIV-only group when controlling for infection factors. Although compared with controls HIV+AUD declined faster than HIV alone, the two HIV groups did not differ significantly from each other in aging rates. Declining Attention/Working Memory and Motor Skills performance correlated with Anterior and Posterior volume declines in the HIV+AUD group.CONCLUSIONS: Regional thalamic volumetry detected normal aging declines, differential and accelerated volume losses in HIV, relations between age-related nuclear and performance declines, and exacerbation of volume declines in comorbid AUD contributing to functional deficits.
View details for DOI 10.1016/j.nicl.2024.103684
View details for PubMedID 39423567
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Multi-dimensional predictors of first drinking initiation and regular drinking onset in adolescence: A prospective longitudinal study.
Developmental cognitive neuroscience
2024; 69: 101424
Abstract
Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.
View details for DOI 10.1016/j.dcn.2024.101424
View details for PubMedID 39089172
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Serum albumin and white matter hyperintensities.
Translational psychiatry
2024; 14 (1): 233
Abstract
People living with HIV and those diagnosed with alcohol use disorders (AUD) relative to healthy individuals commonly have low levels of serum albumin, substantiated as an independent predictor of cardiovascular events. White matter hyperintensities (WMH)-a neuroimaging feature of cerebral small vessel disease-are also related to cardiovascular disease. Despite consensus regarding associations between high levels of urine albumin and WMH prevalence, and low serum albumin levels and impaired cognitive functioning, relations between serum albumin and WMH burdens have rarely been evaluated. Here, a sample including 160 individuals with AUD, 142 living with HIV, and 102 healthy controls was used to test the hypothesis that serum albumin would be inversely related to WMH volumes and directly related to cognitive performance in the two diagnostic groups. Although serum albumin and periventricular WMH volumes showed an inverse relationship in both AUD and HIV groups, this relationship persisted only in the HIV group after consideration of traditional cardiovascular (i.e., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes), study-relevant (i.e., race, socioeconomic status, hepatitis C virus status), and disease-specific (i.e., CD4 nadir, HIV viral load, HIV duration) factors. Further, serum albumin contributed more significantly than periventricular WMH volume to variance in performance on a verbal learning and memory composite score in the HIV group only. Relations in both HIV and AUD groups between albumin and hematological red blood cell markers (e.g., hemoglobin, hematocrit) suggest that in this sample, serum albumin reflects hematological abnormalities. Albumin, a simple serum biomarker available in most clinical settings, may therefore help identify periventricular WMH burden and performance levels in specific cognitive domains in people living with HIV. Whether serum albumin contributes mechanistically to periventricular WMH in HIV will require additional investigation.
View details for DOI 10.1038/s41398-024-02953-5
View details for PubMedID 38824150
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Contributions of Cerebral White Matter Hyperintensities to Postural Instability in Aging with and without Alcohol Use Disorder.
Biological psychiatry. Cognitive neuroscience and neuroimaging
2024
Abstract
Postural instability and brain white matter hyperintensities (WMH) are both noted markers of normal aging and alcohol use disorder (AUD). Here, we questioned what variables contribute to sway path/WMH relations in individuals with AUD and healthy control participants.The data comprised 404 balance platform sessions, yielding sway path length and MRI acquired cross-sectionally or longitudinally, in 102 control and 158 AUD participants, ages 25-80 years. Balance sessions were typically conducted on the same day as MRI FLAIR acquisitions, permitting WMH volume quantification. Factors considered in multiple regression analyses as potential contributors to relations between WMH volumes and postural instability were age, sex, socioeconomic status, education, pedal 2-point discrimination, systolic and diastolic blood pressure, body mass index, depressive symptoms, total alcohol consumed in the past year, and race.Initial analysis identified diagnosis, age, sex, and race as significant contributors to observed sway path/WMH relations. Inclusion of these factors as predictors in multiple regression analysis substantially attenuated the sway/WMH relations in both AUD and healthy control groups. Women, irrespective of diagnosis or race, had shorter sway paths than men. Black participants, irrespective of diagnosis or sex, had shorter sway paths than non-Black participants despite having modestly larger WMH volumes than non-Black participants, possibly a reflection of the younger age of the Black sample.Longer sway paths were related to larger WMH volumes in healthy men and women, with and without AUD. Critically, however, age nearly fully accounted for these relations.
View details for DOI 10.1016/j.bpsc.2024.03.005
View details for PubMedID 38569932
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Contributions of cerebral white matter hyperintensities, age, and pedal perception to postural sway in people living with HIV.
AIDS (London, England)
2024
Abstract
With aging, people living with HIV (PLWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PLWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables.Mixed cross-sectional/longitudinal data acquired over 15 years in 141 PLWH and 102 age-range matched controls, 25-80 years old.Multimodal structural MRI data were quantified for 7 total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and non-path data on sway path-WMH relations.In simple correlations, longer sway paths were associated with larger WMH volumes in PWLH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and 2-point pedal discrimination. Although the sway-WMH relations in PLWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for 5 of the 7 regions in the eyes-open condition.The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.
View details for DOI 10.1097/QAD.0000000000003894
View details for PubMedID 38537080
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Frontal cortical volume deficits as enduring evidence of childhood abuse in community adults with AUD and HIV infection comorbidity.
Neurobiology of stress
2024; 29: 100608
Abstract
Background: Childhood abuse is an underappreciated source of stress, associated with adverse mental and physical health consequences. Childhood abuse has been directly associated with risky behavior thereby increasing the likelihood of alcohol misuse and risk of HIV infection, conditions associated with brain structural and functional deficits. Here, we examined the neural and behavioral correlates of childhood trauma history in alcohol use disorder (AUD), HIV infection (HIV), and their comorbidity (AUD+HIV).Methods: Occurrence of childhood trauma was evaluated by retrospective interview. Cortical (frontal, temporal, parietal, and occipital), subcortical (hippocampus, amygdala), and regional frontal volumes were derived from structural MRI, adjusted for intracranial volume and age. Test scores of executive functioning, attention/working memory, verbal/visual learning, verbal/visual memory, and motor speed functional domains were standardized on age and education of a laboratory control group.Results: History of childhood abuse was associated with smaller frontal lobe volumes regardless of diagnosis. For frontal subregional volumes, history of childhood abuse was selectively associated with smaller orbitofrontal and supplementary motor volumes. In participants with a child abuse history, poorer verbal/visual memory performance was associated with smaller orbitofrontal and frontal middle volumes, whereas in those without childhood abuse, poorer verbal/visual memory performance was associated with smaller orbitofrontal, frontal superior, and supplemental motor volumes.Conclusions: Taken together, these results comport with and extend the findings that childhood abuse is associated with brain and behavioral sequelae in AUD, HIV, and AUD+HIV comorbidity. Further, these findings suggest that sequelae of abuse in childhood may be best conceptualized as a spectrum disorder as significant deficits may be present in those who may not meet criteria for a formal trauma-related diagnosis yet may be suffering enduring stress effects on brain structural and functional health.
View details for DOI 10.1016/j.ynstr.2024.100608
View details for PubMedID 38323165
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Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span.
JAMA network open
2023; 6 (11): e2343618
Abstract
Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD.To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants.This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023.Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable.Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum.The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.
View details for DOI 10.1001/jamanetworkopen.2023.43618
View details for PubMedID 37976065
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White matter microstructural integrity continues to develop from adolescence to young adulthood in mice and humans: Same phenotype, different mechanism.
Neuroimage. Reports
2023; 3 (3)
Abstract
As direct evaluation of a mouse model of human neurodevelopment, adolescent and young adult mice and humans underwent MR diffusion tensor imaging to quantify age-related differences in microstructural integrity of brain white matter fibers. Fractional anisotropy (FA) was greater in older than younger mice and humans. Despite the cross-species commonality, the underlying developmental mechanism differed: whereas evidence for greater axonal extension contributed to higher FA in older mice, evidence for continuing myelination contributed to higher FA in human adolescent development. These differences occurred in the context of species distinctions in overall brain growth: whereas the continued growth of the brain and skull in the murine model can accommodate volume expansion into adulthood, human white matter volume and myelination continue growth into adulthood within a fixed intracranial volume. Appreciation of the similarities and differences in developmental mechanism can enhance the utility of animal models of brain white matter structure, function, and response to exogenous manipulation.
View details for DOI 10.1016/j.ynirp.2023.100179
View details for PubMedID 37916059
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Age-Accelerated Increase of White Matter Hyperintensity Volumes is Exacerbated by Heavy Alcohol Use in People Living with HIV.
Biological psychiatry
2023
Abstract
Antiretroviral treatment has enabled people living with HIV infection to have a near-normal lifespan. With longevity come opportunities for engaging in risky behavior, including initiation of excessive drinking. Given that both HIV infection and alcohol use disorder (AUD) can disrupt brain white matter integrity, we questioned whether HIV infection, even if successfully treated, or AUD alone results in signs of accelerated white matter aging and whether HIV+AUD comorbidity further accelerates brain aging.Longitudinal MRI-FLAIR data were acquired over 15 years in 179 controls, 204 AUD participants, 70 with HIV, and 75 comorbid for HIV+AUD. White matter hyperintensity (WMH) volumes were quantified and localized and their functional relevance was examined with cognitive and motor testing.The three diagnostic groups each had larger WMH volumes than controls. Although all four groups exhibited accelerating volume increases with aging, only the HIV groups showed faster WMH enlargement than controls; the comorbid group showed faster acceleration than the HIV-only group. Sex and HIV infection length, but not viral suppression status, moderated acceleration. Correlations emerged between WMH volumes and Attention/Working Memory and Executive Function scores of the AUD and HIV groups, and between WMH volumes and Motor Skills in the three diagnostic groups.Even treated HIV can show accelerated aging, possibly from treatment sequelae or legacy effects, and notably from AUD comorbidity. WMH volumes may be especially relevant for tracking HIV and AUD brain health because each condition is associated with liability for hypertensive processes, for which WMHs are considered a marker.
View details for DOI 10.1016/j.biopsych.2023.07.023
View details for PubMedID 37597798
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Postural instability in HIV infection: relation to central and peripheral nervous system markers.
AIDS (London, England)
2023
Abstract
Determine the independent contributions of central nervous system (CNS) and peripheral nervous system (PNS) metrics to balance instability in people with HIV (PWH) compared with people without HIV (PWoH).Volumetric MRI (CNS) and two-point pedal discrimination (PNS) were tested as substrates of stance instability measured with balance platform posturography.125 PWH and 88 PWoH underwent balance testing and brain MRI.The PWH exhibited stability deficits that were disproportionately greater with eyes closed than eyes open compared with PWoH. Further analyses revealed that greater postural imbalance measured as longer sway paths correlated with smaller cortical and cerebellar lobular brain volumes known to serve sensory integration; identified brain/sway path relations endured after accounting for contributions from physiological and disease factors as potential moderators; and multiple regression identified PNS and CNS metrics as independent predictors of postural instability in PWH that differed with the use of visual information to stabilize balance. With eyes closed, temporal volumes and two-point pedal discrimination were significant independent predictors of sway; with eyes open, occipital volume was an additional predictor of sway. These relations were selective to PWH and were not detected in PWoH.CNS and PNS factors were independent contributors to postural instability in PWH. Recognizing that myriad inputs must be detected by peripheral systems and brain networks to integrate sensory and musculoskeletal information for maintenance of postural stability, age- or disease-related degradation of either or both nervous systems may contribute to imbalance and liability for falls.
View details for DOI 10.1097/QAD.0000000000003531
View details for PubMedID 36927610
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Multi-atlas thalamic nuclei segmentation on standard T1-weighed MRI with application to normal aging.
Human brain mapping
2022
Abstract
Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.
View details for DOI 10.1002/hbm.26088
View details for PubMedID 36181510
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Attenuated cerebral blood flow in frontolimbic and insular cortices in Alcohol Use Disorder: Relation to working memory.
Journal of psychiatric research
2021; 136: 140–48
Abstract
Chronic, excessive alcohol consumption is associated with cerebrovascular hypoperfusion, which has the potential to interfere with cognitive processes. Magnetic resonance pulsed continuous arterial spin labeling (PCASL) provides a noninvasive approach for measuring regional cerebral blood flow (CBF) and was used to study 24 men and women with Alcohol Use Disorder (AUD) and 20 age- and sex-matched controls. Two analysis approaches tested group differences: a data-driven, regionally-free method to test for group differences on a voxel-by-voxel basis and a region of interest (ROI) approach, which focused quantification on atlas-determined brain structures. Whole-brain, voxel-wise quantification identified low AUD-related cerebral perfusion in large volumes of medial frontal and cingulate cortices. The ROI analysis also identified lower CBF in the AUD group relative to the control group in medial frontal, anterior/middle cingulate, insular, and hippocampal/amygdala ROIs. Further, years of AUD diagnosis negatively correlated with temporal cortical CBF, and scores on an alcohol withdrawal scale negatively correlated with posterior cingulate and occipital gray matter CBF. Regional volume deficits did not account for AUD CBF deficits. Functional relevance of attenuated regional CBF in the AUD group emerged with positive correlations between episodic working memory test scores and anterior/middle cingulum, insula, and thalamus CBF. The frontolimbic and insular cortical neuroconstellation with dampened perfusion suggests a mechanism of dysfunction associated with these brain regions in AUD.
View details for DOI 10.1016/j.jpsychires.2021.01.053
View details for PubMedID 33592385
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White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study
LANCET PSYCHIATRY
2014; 1 (3): 202-212
Abstract
Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse.Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI.This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution.Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery.US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).
View details for Web of Science ID 000343703500022
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Multi-domain predictors of grip strength differentiate individuals with and without alcohol use disorder.
Addiction biology
2024; 29 (11): e70007
Abstract
Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data-driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5-fold stratified cross-validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength (R2 = 0.255, p = 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength (R2 = 0.162, p = 0.002). These cohort-specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort-specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty.
View details for DOI 10.1111/adb.70007
View details for PubMedID 39532141
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Anterior and Posterior Thalamic Volumes Differentially Correlate with Memory, Attention, and Motor Processes in HIV Infection and Alcohol Use Disorder Comorbidity.
Brain research bulletin
2024: 111085
Abstract
The thalamus, with its reciprocal connections to and from cortical, subcortical, and cerebellar regions, is a central active participant in multiple functional brain networks. Structural MRI studies measuring the entire thalamus without respect to its regional or nuclear divisions report volume shrinkage in diseases including HIV infection, alcohol use disorder (AUD), and their comorbidity (HIV+AUD). Here, we examined relations between thalamic subregions (anterior, ventral, medial, and posterior) and neuropsychological functions (attention/working memory, executive functioning, episodic memory, and motor skills). Volumes of thalamic subregions were derived from automatic segmentations of standard T1 weighted MRIs of 65 individuals with HIV, 189 with AUD, 80 with HIV+AUD comorbidity, and 141 healthy controls (CTRL). Total thalamic volume was smaller and cognitive and motor composite scores were lower in the three diagnostic groups relative to the CTRL group. The AUD and HIV+AUD groups had significantly smaller thalamic subregional volumes than the CTRL group. The HIV+AUD group had smaller anterior thalamic volume than the HIV-only group and smaller ventral thalamic volume than the AUD-only group. In the HIV+AUD group, memory scores correlated with anterior thalamic volumes, attention/working memory scores correlated with posterior and medial thalamic volumes, and motor skill scores correlated with posterior thalamic volumes. Exploratory analyses focused on the HIV+AUD group indicated that within the posterior thalamic region, the pulvinar and medial geniculate nuclei were related to attention/working memory scores, and the pulvinar was related to motor skills scores. This study is novel in locating volume deficits in specific thalamic subregions, in addition to the thalamus as a whole, in HIV, AUD, and their comorbidity and in identifying functional ramifications of these deficits. Taken together, this study highlights the relevance of thalamic subregional volume deficits to dissociable cognitive and motor processes.
View details for DOI 10.1016/j.brainresbull.2024.111085
View details for PubMedID 39343322
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Memorial of Kenneth R. Warren, 1943-2024.
Alcohol, clinical & experimental research
2024
View details for DOI 10.1111/acer.15452
View details for PubMedID 39322616
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Metadata-conditioned generative models to synthesize anatomically-plausible 3D brain MRIs.
Medical image analysis
2024; 98: 103325
Abstract
Recent advances in generative models have paved the way for enhanced generation of natural and medical images, including synthetic brain MRIs. However, the mainstay of current AI research focuses on optimizing synthetic MRIs with respect to visual quality (such as signal-to-noise ratio) while lacking insights into their relevance to neuroscience. To generate high-quality T1-weighted MRIs relevant for neuroscience discovery, we present a two-stage Diffusion Probabilistic Model (called BrainSynth) to synthesize high-resolution MRIs conditionally-dependent on metadata (such as age and sex). We then propose a novel procedure to assess the quality of BrainSynth according to how well its synthetic MRIs capture macrostructural properties of brain regions and how accurately they encode the effects of age and sex. Results indicate that more than half of the brain regions in our synthetic MRIs are anatomically plausible, i.e., the effect size between real and synthetic MRIs is small relative to biological factors such as age and sex. Moreover, the anatomical plausibility varies across cortical regions according to their geometric complexity. As is, the MRIs generated by BrainSynth significantly improve the training of a predictive model to identify accelerated aging effects in an independent study. These results indicate that our model accurately capture the brain's anatomical information and thus could enrich the data of underrepresented samples in a study. The code of BrainSynth will be released as part of the MONAI project at https://github.com/Project-MONAI/GenerativeModels.
View details for DOI 10.1016/j.media.2024.103325
View details for PubMedID 39208560
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Identifying high school risk factors that forecast heavy drinking onset in understudied young adults.
Developmental cognitive neuroscience
2024; 68: 101413
Abstract
Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.
View details for DOI 10.1016/j.dcn.2024.101413
View details for PubMedID 38943839
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Identifying the role of (dis)inhibition in the vicious cycle of substance use through ecological momentary assessment and resting-state fMRI.
Translational psychiatry
2024; 14 (1): 260
Abstract
Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one's primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.
View details for DOI 10.1038/s41398-024-02949-1
View details for PubMedID 38897999
View details for PubMedCentralID PMC11186821
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Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.
Addiction biology
2024; 29 (5): e13400
Abstract
Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.
View details for DOI 10.1111/adb.13400
View details for PubMedID 38706091
View details for PubMedCentralID PMC11070496
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Investigating the origin of the13C lactate signal in the anesthetized healthy rat brain in vivo after hyperpolarized [1-13C]pyruvate injection.
NMR in biomedicine
2023: e5073
Abstract
The goal of this study was to investigate the origin of brain lactate (Lac) signal in the healthy anesthetized rat after injection of hyperpolarized (HP) [1-13 C]pyruvate (Pyr). Dynamic two-dimensional spiral chemical shift imaging with flow-sensitizing gradients revealed reduction in both vascular and brain Pyr, while no significant dependence on the level of flow suppression was detected for Lac. These results support the hypothesis that the HP metabolites predominantly reside in different compartments in the brain (i.e., Pyr in the blood and Lac in the parenchyma). Data from high-resolution metabolic imaging of [1-13 C]Pyr further demonstrated that Lac detected in the brain was not from contributions of vascular signal attributable to partial volume effects. Additionally, metabolite distributions and kinetics measured with dynamic imaging after injection of HP [1-13 C]Lac were similar to Pyr data when Pyr was used as the substrate. These data do not support the hypothesis that Lac observed in the brain after Pyr injection was generated in other organs and then transported across the blood-brain barrier (BBB). Together, the presented results provide further evidence that even in healthy anesthetized rats, the transport of HP Pyr across the BBB is sufficiently fast to permit detection of its metabolic conversion to Lac within the brain.
View details for DOI 10.1002/nbm.5073
View details for PubMedID 37990800
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Poor subjective sleep reported by people living with HIV is associated with impaired working memory.
NeuroImmune pharmacology and therapeutics
2023; 2 (2): 127-137
Abstract
Poor sleep can undermine health and may be especially disruptive to those with chronic conditions including HIV infection. Here, clinically well-described people living with HIV [PLWH] (74 men, 35 women) and healthy control (38 men, 35 women) participants were administered the Pittsburgh Sleep Quality Index (PSQI), a validated measure of subjective sleep with a global score ≥5 able to distinguish good from poor sleepers. In addition, participants completed a battery of neuropsychological tests. PLWH (6.8 ± 3.7) had higher global PSQI scores than healthy controls (4.1 ± 2.8): 39.7 % of uninfected controls and 68.8 % of PLWH had a PSQI≥5 indicative of poor sleep. There were no relations between the global PSQI score and any evaluated variables among uninfected individuals or with demographic or HIV-related variables in PLWH. Instead, a higher global PSQI score among PLWH was associated with worse "Quality of Life" scores [Global Assessment of Functioning (GAF, p=0.0007), Medical Outcomes Study survey (21-item short form, SF-21, p<0.0001), and Activities of Daily Living-Instrumental (ADL-I, p=0.0041)] and higher Beck Depression Index (BDI, p<0.0001) depressive symptoms. Further, in PLWH, higher global PSQI scores were associated with poor performance on a working memory task, the digit backward span (p=0.0036). In PLWH, the 5 variables together explained 32.3 % of the global PSQI score variance; only 3 variables - the SF-21, BDI, and digit backward scores - explained 30.6 % of the variance. To the extent that poor subjective sleep contributes to impaired working memory in HIV, we speculate that this impairment may be ameliorated by improved sleep health.
View details for DOI 10.1515/nipt-2023-0010
View details for PubMedID 37946876
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Influence of childhood trauma, HIV infection, alcohol use disorder, and resilience on health-related quality of life in adulthood.
Journal of psychiatric research
2023; 163: 230-239
Abstract
Experience of childhood trauma, especially physical, emotional, and sexual abuse, carries a risk for developing alcohol use disorder (AUD) and engaging in risky behaviors that can result in HIV infection. AUD and HIV are associated with compromised self-reported health-related quality of life (HRQoL) possibly intersecting with childhood trauma. To determine whether poor HRQoL is heightened by AUD, HIV, their comorbidity (AUD+HIV), number of trauma events, or poor resilience, 108 AUD, 45 HIV, 52 AUD+HIV, and 67 controls completed the SF-21 HRQoL, Brief Resilience Scale (BRS), Ego Resiliency Scale (ER-89), and an interview about childhood trauma. Of the 272 participants, 116 reported a trauma history before age 18. Participants had a blood draw, AUDIT questionnaire, and interview about lifetime alcohol consumption. AUD, HIV, and AUD+HIV had lower scores on HRQoL and resilience composite comprising the BRS and ER-89 than controls. Greater resilience was a significant predictor of better quality of life in all groups. HRQoL was differentially moderated in AUD and HIV: more childhood traumas predicted poorer quality of life in AUD and controls, whereas higher T-lymphocyte count contributed to better quality of life in HIV. This study is novel in revealing a detrimental impact on HRQoL from AUD, HIV, and their comorbidity, with differential negative contribution from trauma and beneficial effect of resilience to quality of life. Channeling positive effects of resilience and reducing the incidence and negative impact of childhood trauma may have beneficial effects on health-related quality of life in adulthood independent of diagnosis.
View details for DOI 10.1016/j.jpsychires.2023.05.033
View details for PubMedID 37230007
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Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates.
Brain structure & function
2023
Abstract
Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson's disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.
View details for DOI 10.1007/s00429-023-02626-x
View details for PubMedID 37069296
View details for PubMedCentralID 9804536
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Serum biomarkers of liver fibrosis identify changes in striatal metabolite levels.
Research square
2023
Abstract
1H-magnetic resonance spectroscopy (MRS) conducted in cirrhosis shows consistent CNS changes such as high levels of the combined resonances (Glx) of glutamate (Glu) + glutamine (Gln) and low levels of choline-containing compounds (Cho) and myo-Inositol (mI) relative to total creatine (tCr). Studies of hepatitis C virus (HCV) infection, however, note higher than control levels of tCr, Cho, and mI. Here, serum markers of liver fibrosis were evaluated to determine whether they would discriminate neurometabolites in striatum, cerebellum, and pons. An aspartate aminotransferase to platelet ratio index (APRI)>0.7 identified liver fibrosis in 9.0% (n=13) of the cohort; a fibrosis score (FIB4)>1.5 identified liver fibrosis in 32.4% (n=34) of the population. Those with APRI>0.7 had higher levels of striatal tCr (p=.001) and Cho (p=.0003). Similarly, those with FIB>1.5 had higher levels of striatal Cho (p=.01). A multiple regression including the variables APRI>0.7 and HCV explained 16.5% of the variance in striatal Cho and was driven by the APRI. Likewise, the FIB4 relative to HCV explained more of the variance in striatal Cho. Higher striatal Cho levels showed a positive relationship with pallidal signal intensities (r=.18, p=.04). Further, higher pallidal T1-signals were associated with greater standing balance instability with eyes closed (r=-.22, p=.008). Together, these results suggest that elevations in striatal Cho and basal ganglia T1-signal intensities are related to presence of liver fibrosis with functional consequences.
View details for DOI 10.21203/rs.3.rs-2729490/v1
View details for PubMedID 37034697
View details for PubMedCentralID PMC10081358
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Serum Biomarkers of Liver Fibrosis Identify Changes to Striatal Metabolites Consistent With Lipid Accumulation
SPRINGERNATURE. 2022: 166-167
View details for Web of Science ID 000929613800341
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Serum Biomarkers of Liver Fibrosis Identify Changes to Striatal Metabolites Consistent With Lipid Accumulation
SPRINGERNATURE. 2022: 166-167
View details for Web of Science ID 000897934700340
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Alcohol's effects on the mouse brain are modulated by age and sex
ADDICTION BIOLOGY
2022; 27 (5)
View details for DOI 10.1111/adb.13209
View details for Web of Science ID 000823573700001
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Alcohol's effects on the mouse brain are modulated by age and sex.
Addiction biology
2022; 27 (5): e13209
Abstract
Binge alcohol consumption is common among adolescents and may impair normal brain development. Emerging, longitudinal studies in adolescents suggest that the effects of binge alcohol exposure on brain structure differ between sexes. To test the hypothesis that the effects of binge alcohol exposure on developmental brain growth trajectories are influenced by age of exposure and sex, adolescent and adult, male and female C57Bl/6 mice (n = 32), were exposed to a binge-like ethanol (EtOH) exposure paradigm (i.e., 5 cycles of 2 on/2 off days of 5 g/kg EtOH intraperitoneal) or served as saline controls. Longitudinal structural magnetic resonance imaging was acquired at baseline, following binge EtOH exposure, and after 2 weeks of recovery. Alcohol treatment showed interactions with age and sex in altering whole brain volume: adolescents of both sexes demonstrated inhibited whole brain growth relative to their control counterparts, although significance was only attained in female mice which showed a larger magnitude response to EtOH compared to male mice. In region of interest analyses, the somatosensory cortex and cerebellum showed inhibited growth in male and female adolescent mice exposed to EtOH, but the difference relative to controls did not reach multiple comparison-corrected statistical significance. These data suggest that in mice exposed to binge EtOH treatment, adolescent age of exposure and female sex may confer a higher risk to the detrimental effects of EtOH on brain structure and reinforce the need for direct testing of both sexes.
View details for DOI 10.1111/adb.13209
View details for PubMedID 36001428
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Earlier Bedtime and Effective Coping Skills Predict a Return to Low-Risk of Depression in Young Adults during the COVID-19 Pandemic.
International journal of environmental research and public health
2022; 19 (16)
Abstract
To determine the persistent effects of the pandemic on mental health in young adults, we categorized depressive symptom trajectories and sought factors that promoted a reduction in depressive symptoms in high-risk individuals. Specifically, longitudinal analysis investigated changes in the risk for depression before and during the pandemic until December 2021 in 399 young adults (57% female; age range: 22.8 ± 2.6 years) in the United States (U.S.) participating in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The Center for Epidemiologic Studies Depression Scale (CES-D-10) was administered multiple times before and during the pandemic. A score ≥10 identified individuals at high-risk for depression. Self-reported sleep behavior, substance use, and coping skills at the start of the pandemic were assessed as predictors for returning to low-risk levels while controlling for demographic factors. The analysis identified four trajectory groups regarding depression risk, with 38% being at low-risk pre-pandemic through 2021, 14% showing persistent high-risk pre-pandemic through 2021, and the remainder converting to high-risk either in June 2020 (30%) or later (18%). Of those who became high-risk in June 2020, 51% were no longer at high-risk in 2021. Logistic regression revealed that earlier bedtime and, for the older participants (mid to late twenties), better coping skills were associated with this declining risk. Results indicate divergence in trajectories of depressive symptoms, with a considerable number of young adults developing persistent depressive symptoms. Healthy sleep behavior and specific coping skills have the potential to promote remittance from depressive symptoms in the context of the pandemic.
View details for DOI 10.3390/ijerph191610300
View details for PubMedID 36011934
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Poor subjective sleep predicts compromised quality of life but not cognitive impairment in abstinent individuals with Alcohol Use Disorder.
Alcohol (Fayetteville, N.Y.)
2022
Abstract
How disrupted sleep contributes to cognitive dysfunction over the dynamic course of Alcohol Use Disorder (AUD) is an emerging topic of investigation. Here, the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate subjective sleep in 90 individuals with AUD sober for an average of 3 months and in 50 healthy controls. Relative to controls, AUD individuals had higher global PSQI scores (worse sleep), higher scores on the Beck Depression Inventory (BDI), worse Quality of Life (QoL) indicators, and poorer performance on cognitive composite tests (executive functioning, attention and working memory, visual and verbal learning or memory). Among AUD individuals, a higher PSQI score correlated with a higher BDI scores and worse QoL, but not with cognitive scales. Also noted in the AUD group were higher global PSQI scores in individuals also diagnosed with major depressive (MDD) or generalized anxiety (GAD) disorders. Together, the 4 variables explained 29.8% of the variance in AUD PSQI scores. In women with AUD, the 4 factors explained 39.3% of the variance in PSQI scores; in AUD men, the 4 measures explained 19.9% of the variance: MDD was salient in women, QoL in men with AUD suggesting differential factors associate with poor sleep in men and women with AUD even with sustained alcohol abstinence. Here, global PSQI scores were related to clinical diagnoses and life functioning but failed to predict cognitive performance in abstinent AUD individuals.
View details for DOI 10.1016/j.alcohol.2022.07.001
View details for PubMedID 35870739
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Alcohol use disorder: Neuroimaging evidence for accelerated aging of brain morphology and hypothesized contribution to age-related dementia.
Alcohol (Fayetteville, N.Y.)
2022
Abstract
Excessive alcohol use curtails longevity by rendering intoxicated individuals vulnerable to heightened risk from accidents, violence, and alcohol poisoning and chronically heavy drinkers vulnerable to accelerating age-related medical and psychiatric conditions that can be life-threatening (Yoon et al., 2020). Thus, studies of factors influencing age-alcohol interactions must consider the potential that the alcohol use disorder (AUD) population may not represent the oldest ages of the unaffected population and may well have accrued comorbidities associated with both AUD and aging itself. Herein, we focus on the aging of the brains of men and women with AUD, keeping AUD contextual factors in mind. Knowledge of the potential influence of the AUD-associated co-factors on the condition of brain structure may lead to identifying modifiable risk factors to avert physical declines and may reverse or arrest further AUD-related degradation of the brain. In this narrative review, we 1) describe quantitative, controlled studies of brain macrostructure and microstructure of adults with AUD, 2) consider the possibility of recovery of brain integrity through harm reduction with sustained abstinence or reduced drinking, and 3) speculate on the ramifications of accelerated aging in AUD as contributing to age-related dementia.
View details for DOI 10.1016/j.alcohol.2022.06.002
View details for PubMedID 35781021
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Prior test experience confounds longitudinal tracking of adolescent cognitive and motor development.
BMC medical research methodology
2022; 22 (1): 177
Abstract
BACKGROUND: Accurate measurement of trajectories in longitudinal studies, considered the gold standard method for tracking functional growth during adolescence, decline in aging, and change after head injury, is subject to confounding by testing experience.METHODS: We measured change in cognitive and motor abilities over four test sessions (baseline and three annual assessments) in 154 male and 165 female participants (baseline age 12-21years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. At each of the four test sessions, these participants were given a test battery using computerized administration and traditional pencil and paper tests that yielded accuracy and speed measures for multiple component cognitive (Abstraction, Attention, Emotion, Episodic memory, Working memory, and General Ability) and motor (Ataxia and Speed) functions. The analysis aim was to dissociate neurodevelopment from testing experience by using an adaptation of the twice-minus-once tested method, which calculated the difference between longitudinal change (comprising developmental plus practice effects) and practice-free initial cross-sectional performance for each consecutive pairs of test sessions. Accordingly, the first set of analyses quantified the effects of learning (i.e., prior test experience) on accuracy and after speed domain scores. Then developmental effects were determined for each domain for accuracy and speed having removed the measured learning effects.RESULTS: The greatest gains in performance occurred between the first and second sessions, especially in younger participants, regardless of sex, but practice gains continued to accrue thereafter for several functions. For all 8 accuracy composite scores, the developmental effect after accounting for learning was significant across age and was adequately described by linear fits. The learning-adjusted developmental effects for speed were adequately described by linear fits for Abstraction, Emotion, Episodic Memory, General Ability, and Motor scores, although a nonlinear fit was better for Attention, Working Memory, and Average Speed scores.CONCLUSION: Thus, what appeared as accelerated cognitive and motor development was, in most cases, attributable to learning. Recognition of the substantial influence of prior testing experience is critical for accurate characterization of normal development and for developing norms for clinical neuropsychological investigations of conditions affecting the brain.
View details for DOI 10.1186/s12874-022-01606-9
View details for PubMedID 35751025
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A prospective study revealing a compounded burden of COVID-19, sex, and clinical diagnosis of alcohol use disorder and HIV infection on quality of life, anxiety, and alcohol use.
Journal of psychiatric research
2022; 152: 152-159
Abstract
The COVID-19 pandemic led to unprecedented restrictions to mitigate disease spread, leading to consequences affecting mental health. Many studies examining COVID-19 pandemic effects on well-being and mental health initiated inquiry after the pandemic onset, whereas we used self-report questionnaires obtained before the pandemic to re-assess the same functions during the pandemic. Participants were drawn from our ongoing longitudinal studies of people with HIV infection, alcohol use disorder (AUD), HIV+AUD comorbidity, and controls. We used phone or mail contact to invite all to participate in our COVID phone survey, which included three self-report questionnaires: Health-related Quality of Life (QoL), State-Trait Anxiety Inventory (STAI), and Alcohol Use Disorder Identification Test (AUDIT). Of 218 eligible participants, 86 responded (July 2020-March 2021): clinical (29 men, 23 women; 17 AUD, 21 HIV, 14 HIV+AUD); control (17 men, 17 women). QoL scores declined, and anxiety symptoms increased from pre-COVID surveys in all groups; clinical women reported greater negative changes than the other groups. QoL subscales revealed COVID-related declines in emotional well-being in all groups, with clinical women reporting additional declines in energy, physical and social functioning, health, and pain increase. Clinical men also reported health declines. Although AUDIT scores were stable in all groups between assessments, changes in AUDIT scores were inversely correlated with QoL scores in clinical women; in clinical men, changes in STAI scores were inversely correlated with QoL scores. Although all groups were adversely affected by the pandemic, the negative effects were greater in the clinical group regardless of diagnosis and greatest in clinical women.
View details for DOI 10.1016/j.jpsychires.2022.06.017
View details for PubMedID 35724497
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Disruption of cerebellar-cortical functional connectivity predicts balance instability in alcohol use disorder.
Drug and alcohol dependence
2022; 235: 109435
Abstract
A neural substrate of alcohol-related instability of gait and balance is the cerebellum. Whether disruption of neural communication between cerebellar and cortical brain regions exerts an influence on ataxia in alcohol use disorder (AUD) was the focus of this study.Study groups comprised 32 abstinent AUD participants and 22 age- and sex-matched healthy controls (CTL). All participants underwent clinical screening, motor testing, and resting-state functional MR imaging analyzed for functional connectivity (FC) among 90 regions across the whole cerebrum and cerebellum. Ataxia testing quantified gait and balance with the Fregly-Graybiel Ataxia Battery conducted with and without vision.The AUD group achieved lower scores than the CTL group on balance performance, which was disproportionately worse for eyes open than eyes closed in the AUD relative to the CTL group. Differences in ataxia were accompanied by differences in FC marked by cerebellar-frontal and cerebellar-parietal hyperconnectivity and cortico-cortical hypoconnectivity in the AUD relative to the control group. Lifetime alcohol consumption correlated significantly with AUD-related FC aberrations, which explained upwards of 69% of the AUD ataxia score variance.Heavy, chronic alcohol consumption is associated with disorganized neural communication among cerebellar-cortical regions and contributes to ataxia in AUD. Ataxia, which is known to accelerate with age and be exacerbated with AUD, can threaten functional independence. Longitudinal studies are warranted to address whether extended sobriety quells ataxia and normalizes aberrant FC contributing to instability.
View details for DOI 10.1016/j.drugalcdep.2022.109435
View details for PubMedID 35395501
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Systemic Administration of the TLR7/8 Agonist Resiquimod (R848) to Mice Is Associated with Transient, In Vivo-Detectable Brain Swelling.
Biology
2022; 11 (2)
Abstract
Peripheral administration of the E. coli endotoxin lipopolysaccharide (LPS) to rats promotes secretion of pro-inflammatory cytokines and in previous studies was associated with transient enlargement of cortical volumes. Here, resiquimod (R848) was administered to mice to stimulate peripheral immune activation, and the effects on brain volumes and neurometabolites determined. After baseline scans, 24 male, wild-type C57BL mice were triaged into three groups including R848 at low (50 mug) and high (100 mug) doses and saline controls. Animals were scanned again at 3 h and 24 h following treatment. Sickness indices of elevated temperature and body weight loss were observed in all R848 animals. Animals that received 50 mug R848 exhibited decreases in hippocampal N-acetylaspartate and phosphocreatine at the 3 h time point that returned to baseline levels at 24 h. Animals that received the 100 mug R848 dose demonstrated transient, localized, volume expansion (~5%) detectable at 3 h in motor, somatosensory, and olfactory cortices; and pons. A metabolic response evident at the lower dose and a volumetric change at the higher dose suggests a temporal evolution of the effect wherein the neurochemical change is demonstrable earlier than neurostructural change. Transient volume expansion in response to peripheral immune stimulation corresponds with previous results and is consistent with brain swelling that may reflect CNS edema.
View details for DOI 10.3390/biology11020274
View details for PubMedID 35205140
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Aging Accelerates Postural Instability in HIV Infection: Contributing Sensory Biomarkers.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
2022
Abstract
People living with HIV infection (PWH) who are adequately treated pharmacologically are now likely to have a near normal life span. Along with this benefit of the aging HIV population are potential physical problems attendant to aging, including postural stability. Whether aging with HIV accelerates age-related liability for postural instability and what sensory factors contribute to imbalance were examined in 227 PWH and 137 people living without HIV (PWoH), age 25 to 75 years. A mixed cross-sectional/longitudinal design revealed steeper aging trajectories of the PWH than PWoH in sway path length, measured as center-of-pressure micro-displacements with a force platform while a person attempted to stand still. Sway paths were disproportionately longer for PWH than PWoH when tested with eyes closed than open. Multiple regression identified objective measures of sensory perception as unique predictors of sway path length, whereas age, sway path length, and self-reports of falls were predictors of standing on one leg, a common measure of ataxia. Knowledge about sensory signs and symptoms of imbalance in postural stability with and without visual information may serve as modifiable risk factors for averting instability and liability for falls in the aging HIV population.
View details for DOI 10.1007/s11481-021-10039-y
View details for PubMedID 34997916
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Growth Trajectories of Cognitive and Motor Control in Adolescence: How Much Is Development and How Much Is Practice?
NEUROPSYCHOLOGY
2021
View details for DOI 10.1037/neu0000771
View details for Web of Science ID 000735242200001
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Risk for depression tripled during the COVID-19 pandemic in emerging adults followed for the last 8 years.
Psychological medicine
2021: 1-8
Abstract
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.METHODS: Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.RESULTS: The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.CONCLUSIONS: The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
View details for DOI 10.1017/S0033291721004062
View details for PubMedID 34726149
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Multi-label, multi-domain learning identifies compounding effects of HIV and cognitive impairment.
Medical image analysis
2021; 75: 102246
Abstract
Older individuals infected by Human Immunodeficiency Virus (HIV) are at risk for developing HIV-Associated Neurocognitive Disorder (HAND), i.e., from reduced cognitive functioning similar to HIV-negative individuals with Mild Cognitive Impairment (MCI) or to Alzheimer's Disease (AD) if more severely affected. Incompletely understood is how brain structure can serve to differentiate cognitive impairment (CI) in the HIV-positive (i.e., HAND) from the HIV-negative cohort (i.e., MCI and AD). To that end, we designed a multi-label classifier that labels the structural magnetic resonance images (MRI) of individuals by their HIV and CI status via two binary variables. Proper training of such an approach traditionally requires well-curated datasets containing large number of samples for each of the corresponding four cohorts (healthy controls, CI HIV-negative adults a.k.a. CI-only, HIV-positive patients without CI a.k.a. HIV-only, and HAND). Because of the rarity of such datasets, we proposed to improve training of the multi-label classifier via a multi-domain learning scheme that also incorporates domain-specific classifiers on auxiliary single-label datasets specific to either binary label. Specifically, we complement the training dataset of MRIs of the four cohorts (Control: 156, CI-only: 335, HIV-only: 37, HAND: 145) acquired by the Memory and Aging Center at the University of California - San Francisco with a CI-specific dataset only containing MRIs of HIV-negative subjects (Controls: 229, CI-only: 397) from the Alzheimer's Disease Neuroimaging Initiative and an HIV-specific dataset (Controls: 75, HIV-only: 75) provided by SRI International. Based on cross-validation on the UCSF dataset, the multi-domain and multi-label learning strategy leads to superior classification accuracy compared with one-domain or multi-class learning approaches, specifically for the undersampled HIV-only cohort. The 'prediction logits' of CI computed by the multi-label formulation also successfully stratify motor performance among the HIV-positive subjects (including HAND). Finally, brain patterns driving the subject-level predictions across all four cohorts characterize the independent and compounding effects of HIV and CI in the HAND cohort.
View details for DOI 10.1016/j.media.2021.102246
View details for PubMedID 34706304
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Self-Supervised Longitudinal Neighbourhood Embedding.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
2021; 12902: 80-89
Abstract
Longitudinal MRIs are often used to capture the gradual deterioration of brain structure and function caused by aging or neurological diseases. Analyzing this data via machine learning generally requires a large number of ground-truth labels, which are often missing or expensive to obtain. Reducing the need for labels, we propose a self-supervised strategy for representation learning named Longitudinal Neighborhood Embedding (LNE). Motivated by concepts in contrastive learning, LNE explicitly models the similarity between trajectory vectors across different subjects. We do so by building a graph in each training iteration defining neighborhoods in the latent space so that the progression direction of a subject follows the direction of its neighbors. This results in a smooth trajectory field that captures the global morphological change of the brain while maintaining the local continuity. We apply LNE to longitudinal T1w MRIs of two neuroimaging studies: a dataset composed of 274 healthy subjects, and Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 632). The visualization of the smooth trajectory vector field and superior performance on downstream tasks demonstrate the strength of the proposed method over existing self-supervised methods in extracting information associated with normal aging and in revealing the impact of neurodegenerative disorders. The code is available at https://github.com/ouyangjiahong/longitudinal-neighbourhood-embedding.
View details for DOI 10.1007/978-3-030-87196-3_8
View details for PubMedID 35727732
View details for PubMedCentralID PMC9204645
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Memory impairment in alcohol use disorder is associated with regional frontal brain volumes.
Drug and alcohol dependence
2021; 228: 109058
Abstract
BACKGROUND: Episodic memory deficits occur in alcohol use disorder (AUD), but their anatomical substrates remain in question. Although persistent memory impairment is classically associated with limbic circuitry disruption, learning and retrieval of new information also relies on frontal systems. Despite AUD vulnerability of frontal lobe integrity, relations between frontal regions and memory processes have been under-appreciated.METHODS: Participants included 91 AUD (49 with a drug diagnosis history) and 36 controls. Verbal and visual episodic memory scores were age- and education-corrected. Structural magnetic resonance imaging (MRI) data yielded regional frontal lobe (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and total hippocampal volumes.RESULTS: AUD were impaired on all memory scores and had smaller precentral frontal and hippocampal volumes than controls. Orbital, superior, and inferior frontal volumes and lifetime alcohol consumption were independent predictors of episodic memory in AUD. Selectivity was established with a double dissociation, where orbital frontal volume predicted verbal but not visual memory, whereas inferior frontal volumes predicted visual but not verbal memory. Further, superior frontal volumes predicted verbal memory in AUD alone, whereas orbital frontal volumes predicted verbal memory in AUD+drug abuse history.CONCLUSIONS: Selective relations among frontal subregions and episodic memory processes highlight the relevance of extra-limbic regions in mnemonic processes in AUD. Memory deficits resulting from frontal dysfunction, unlike the episodic memory impairment associated with limbic dysfunction, may be more amenable to recovery with cessation or reduction of alcohol misuse and may partially explain the heterogeneity in episodic memory abilities in AUD.
View details for DOI 10.1016/j.drugalcdep.2021.109058
View details for PubMedID 34610518
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GROWTH TRAJECTORIES OF COGNITIVE AND MOTOR CONTROL IN ADOLESCENCE: HOW MUCH IS DEVELOPMENT AND HOW MUCH IS PRACTICE?
WILEY. 2021: 188A
Abstract
Executive control continues to develop throughout adolescence and is vulnerable to alcohol use. Although longitudinal assessment is ideal for tracking executive function development and onset of alcohol use, prior testing experience must be distinguished from developmental trajectories.We used the Stroop Match-to-Sample task to examine the improvement of processing speed and specific cognitive and motor control over 4 years in 445 adolescents. The twice-minus-once-tested method was used and expanded to four test sessions to delineate prior experience (i.e., learning) from development. A General Additive Model evaluated the predictive value of age and sex on executive function development and potential influences of alcohol use on development.Results revealed strong learning between the first two assessments. Adolescents significantly improved their speed processing over 4 years. Compared with boys, girls enhanced ability to control cognitive interference and motor reactions. Finally, the influence of alcohol use initiation was tested over 4 years for development in 110 no/low, 110 moderate/heavy age- and sex-matched drinkers; alcohol effects were not detected in the matched groups.Estimation of learning effects is crucial for examining developmental changes longitudinally. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View details for Web of Science ID 000661449201259
View details for PubMedID 34807641
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Longitudinal Pooling & Consistency Regularization to Model Disease Progression From MRIs.
IEEE journal of biomedical and health informatics
2021; 25 (6): 2082-2092
Abstract
Many neurological diseases are characterized by gradual deterioration of brain structure andfunction. Large longitudinal MRI datasets have revealed such deterioration, in part, by applying machine and deep learning to predict diagnosis. A popular approach is to apply Convolutional Neural Networks (CNN) to extract informative features from each visit of the longitudinal MRI and then use those features to classify each visit via Recurrent Neural Networks (RNNs). Such modeling neglects the progressive nature of the disease, which may result in clinically implausible classifications across visits. To avoid this issue, we propose to combine features across visits by coupling feature extraction with a novel longitudinal pooling layer and enforce consistency of the classification across visits in line with disease progression. We evaluate the proposed method on the longitudinal structural MRIs from three neuroimaging datasets: Alzheimer's Disease Neuroimaging Initiative (ADNI, N=404), a dataset composed of 274 normal controls and 329 patients with Alcohol Use Disorder (AUD), and 255 youths from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). In allthree experiments our method is superior to other widely used approaches for longitudinal classification thus making a unique contribution towards more accurate tracking of the impact of conditions on the brain. The code is available at https://github.com/ouyangjiahong/longitudinal-pooling.
View details for DOI 10.1109/JBHI.2020.3042447
View details for PubMedID 33270567
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Preliminary Evidence for a Relationship between Elevated Plasma TNFα and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity.
International journal of molecular sciences
2021; 22 (9)
Abstract
Classical inflammation in response to bacterial, parasitic, or viral infections such as HIV includes local recruitment of neutrophils and macrophages and the production of proinflammatory cytokines and chemokines. Proposed biomarkers of organ integrity in Alcohol Use Disorders (AUD) include elevations in peripheral plasma levels of proinflammatory proteins. In testing this proposal, previous work included a group of human immunodeficiency virus (HIV)-infected individuals as positive controls and identified elevations in the soluble proteins TNFα and IP10; these cytokines were only elevated in AUD individuals seropositive for hepatitis C infection (HCV). The current observational, cross-sectional study evaluated whether higher levels of these proinflammatory cytokines would be associated with compromised brain integrity. Soluble protein levels were quantified in 86 healthy controls, 132 individuals with AUD, 54 individuals seropositive for HIV, and 49 individuals with AUD and HIV. Among the patient groups, HCV was present in 24 of the individuals with AUD, 13 individuals with HIV, and 20 of the individuals in the comorbid AUD and HIV group. Soluble protein levels were correlated to regional brain volumes as quantified with structural magnetic resonance imaging (MRI). In addition to higher levels of TNFα and IP10 in the 2 HIV groups and the HCV-seropositive AUD group, this study identified lower levels of IL1β in the 3 patient groups relative to the control group. Only TNFα, however, showed a relationship with brain integrity: in HCV or HIV infection, higher peripheral levels of TNFα correlated with smaller subcortical white matter volume. These preliminary results highlight the privileged status of TNFα on brain integrity in the context of infection.
View details for DOI 10.3390/ijms22094953
View details for PubMedID 34067023
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Preliminary Evidence for a Relationship between Elevated Plasma TNF alpha and Smaller Subcortical White Matter Volume in HCV Infection Irrespective of HIV or AUD Comorbidity
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2021; 22 (9)
View details for DOI 10.3390/ijms22094953
View details for Web of Science ID 000650336900001
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Rates of Incidental Findings in Brain Magnetic Resonance Imaging in Children.
JAMA neurology
2021
Abstract
Importance: Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings.Objectives: To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended.Design, Setting, and Participants: This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020.Main Outcomes and Measures: Percentage of children with IFs in each category and prevalence of specific IFs.Results: A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2=0.260; 95% CI, 0.135-0.387).Conclusions and Relevance: Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.
View details for DOI 10.1001/jamaneurol.2021.0306
View details for PubMedID 33749724
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Altered Cerebro-Cerebellar Dynamic Functional Connectivity in Alcohol Use Disorder: a Resting-State fMRI Study.
Cerebellum (London, England)
2021
Abstract
Alcohol use disorder (AUD) is widely associated with cerebellar dysfunction and altered cerebro-cerebellar functional connectivity (FC) that lead to cognitive impairments. Evidence for this association comes from resting-state functional magnetic resonance imaging (rsfMRI) studies that assess time-averaged measures of FC across the duration of a typical scan. This approach, however, precludes the assessment of potentially FC dynamics happening at faster timescales. In this study, using rsfMRI data, we aim at exploring cerebro-cerebellar FC dynamics in AUD patients (N = 18) and age- and sex-matched controls (N = 18). In particular, we quantified group-level differences in the temporal variability of FC between the posterior cerebellum and large-scale cognitive systems, and we investigated the role of the cerebellum in large-scale brain dynamics in terms of the temporal flexibility and integration of its regions. We found that, relative to controls, the AUD group exhibited significantly greater FC variability between the cerebellum and both the frontoparietal executive control (F1,31 = 7.01, p(FDR) = 0.028) and ventral attention (F1,31 = 7.35, p(FDR) = 0.028) networks. Moreover, the AUD group exhibited significantly less flexibility (F1,31 = 8.61, p(FDR) = 0.028) and greater integration (F1,31 = 9.11, p(FDR) = 0.028) in the cerebellum. Finally, in an exploratory analysis, we found distributed changes in the dynamics of canonical large-scale networks in AUD. Overall, this study brings evidence of AUD-related alterations in dynamic FC within major cerebro-cerebellar networks. This pattern has implications for explaining the development and maintenance of this disorder and improving our understating of the cerebellum's involvement in addiction.
View details for DOI 10.1007/s12311-021-01241-y
View details for PubMedID 33655376
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Performance ramifications of abnormal functional connectivity of ventral posterior lateral thalamus with cerebellum in abstinent individuals with Alcohol Use Disorder.
Drug and alcohol dependence
2021; 220: 108509
Abstract
The extant literature supports the involvement of the thalamus in the cognitive and motor impairment associated with chronic alcohol consumption, but clear structure/function relationships remain elusive. Alcohol effects on specific nuclei rather than the entire thalamus may provide the basis for differential cognitive and motor decline in Alcohol Use Disorder (AUD). This functional MRI (fMRI) study was conducted in 23 abstinent individuals with AUD and 27 healthy controls to test the hypothesis that functional connectivity between anterior thalamus and hippocampus would be compromised in those with an AUD diagnosis and related to mnemonic deficits. Functional connectivity between 7 thalamic structures [5 thalamic nuclei: anterior ventral (AV), mediodorsal (MD), pulvinar (Pul), ventral lateral posterior (VLP), and ventral posterior lateral (VPL); ventral thalamus; the entire thalamus] and 14 "functional regions" was evaluated. Relative to controls, the AUD group exhibited different VPL-based functional connectivity: an anticorrelation between VPL and a bilateral middle temporal lobe region observed in controls became a positive correlation in the AUD group; an anticorrelation between the VPL and the cerebellum was stronger in the AUD than control group. AUD-associated altered connectivity between anterior thalamus and hippocampus as a substrate of memory compromise was not supported; instead, connectivity differences from controls selective to VPL and cerebellum demonstrated a relationship with impaired balance. These preliminary findings support substructure-level evaluation in future studies focused on discerning the role of the thalamus in AUD-associated cognitive and motor deficits.
View details for DOI 10.1016/j.drugalcdep.2021.108509
View details for PubMedID 33453503
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Self-supervised Longitudinal Neighbourhood Embedding
SPRINGER INTERNATIONAL PUBLISHING AG. 2021: 80-89
View details for DOI 10.1007/978-3-030-87196-3_8
View details for Web of Science ID 000712020700008
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Representation Learning with Statistical Independence to Mitigate Bias.
IEEE Winter Conference on Applications of Computer Vision. IEEE Winter Conference on Applications of Computer Vision
2021; 2021: 2512-2522
Abstract
Presence of bias (in datasets or tasks) is inarguably one of the most critical challenges in machine learning applications that has alluded to pivotal debates in recent years. Such challenges range from spurious associations between variables in medical studies to the bias of race in gender or face recognition systems. Controlling for all types of biases in the dataset curation stage is cumbersome and sometimes impossible. The alternative is to use the available data and build models incorporating fair representation learning. In this paper, we propose such a model based on adversarial training with two competing objectives to learn features that have (1) maximum discriminative power with respect to the task and (2) minimal statistical mean dependence with the protected (bias) variable(s). Our approach does so by incorporating a new adversarial loss function that encourages a vanished correlation between the bias and the learned features. We apply our method to synthetic data, medical images (containing task bias), and a dataset for gender classification (containing dataset bias). Our results show that the learned features by our method not only result in superior prediction performance but also are unbiased.
View details for DOI 10.1109/wacv48630.2021.00256
View details for PubMedID 34522832
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Quantifying Parkinson's disease motor severity under uncertainty using MDS-UPDRS videos.
Medical image analysis
2021; 73: 102179
Abstract
Parkinson's disease (PD) is a brain disorder that primarily affects motor function, leading to slow movement, tremor, and stiffness, as well as postural instability and difficulty with walking/balance. The severity of PD motor impairments is clinically assessed by part III of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a universally-accepted rating scale. However, experts often disagree on the exact scoring of individuals. In the presence of label noise, training a machine learning model using only scores from a single rater may introduce bias, while training models with multiple noisy ratings is a challenging task due to the inter-rater variabilities. In this paper, we introduce an ordinal focal neural network to estimate the MDS-UPDRS scores from input videos, to leverage the ordinal nature of MDS-UPDRS scores and combat class imbalance. To handle multiple noisy labels per exam, the training of the network is regularized via rater confusion estimation (RCE), which encodes the rating habits and skills of raters via a confusion matrix. We apply our pipeline to estimate MDS-UPDRS test scores from their video recordings including gait (with multiple Raters, R=3) and finger tapping scores (single rater). On a sizable clinical dataset for the gait test (N=55), we obtained a classification accuracy of 72% with majority vote as ground-truth, and an accuracy of ∼84% of our model predicting at least one of the raters' scores. Our work demonstrates how computer-assisted technologies can be used to track patients and their motor impairments, even when there is uncertainty in the clinical ratings. The latest version of the code will be available at https://github.com/mlu355/PD-Motor-Severity-Estimation.
View details for DOI 10.1016/j.media.2021.102179
View details for PubMedID 34340101
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Association of Heavy Drinking With Deviant Fiber Tract Development in Frontal Brain Systems in Adolescents.
JAMA psychiatry
2020
Abstract
Importance: Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood.Objective: To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents.Design, Setting, and Participants: This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking.Exposures: Self-reported alcohol consumption in the past year summarized by categorical drinking levels.Main Outcomes and Measures: Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope.Results: Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154=-2.7, P=.008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156=-0.21, 2-tailed P=.008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152=3.0, P=.004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence.Conclusions and Relevance: This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.
View details for DOI 10.1001/jamapsychiatry.2020.4064
View details for PubMedID 33377940
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Alcohol Use Disorder and Its Comorbidity With HIV Infection Disrupts Anterior Cingulate Cortex Functional Connectivity.
Biological psychiatry. Cognitive neuroscience and neuroimaging
2020
Abstract
BACKGROUND: Individuals with alcohol use disorder (AUD) have a heightened risk of contracting HIV infection. The effects of these two diseases and their comorbidity on brain structure have been well described, but their effects on brain function have never been investigated at the scale of whole-brain connectomes.METHODS: In contrast with prior studies that restricted analyses to specific brain networks or examined relatively small groups of participants, our analyses are based on whole-brain functional connectomes of 292 participants.RESULTS: Relative to participants without AUD, the functional connectivity between the anterior cingulate cortex and orbitofrontal cortex was lower for participants with AUD. Compared with participants without AUD+HIV comorbidity, the functional connectivity between the anterior cingulate cortex and hippocampus was lower for the AUD+HIV participants. Compromised connectivity between these pairs was significantly correlated with greater total lifetime alcohol consumption; the effects of total lifetime alcohol consumption on executive functioning were significantly mediated by the functional connectivity between the pairs.CONCLUSIONS: Taken together, our results suggest that the functional connectivity of the anterior cingulate cortex is disrupted in individuals with AUD alone and AUD with HIV infection comorbidity. Moreover, the affected connections are associated with deficits in executive functioning, including heightened impulsiveness.
View details for DOI 10.1016/j.bpsc.2020.11.012
View details for PubMedID 33558196
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Spatio-Temporal Graph Convolution for Resting-State fMRI Analysis.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
2020; 12267: 528–38
Abstract
The Blood-Oxygen-Level-Dependent (BOLD) signal of resting-state fMRI (rs-fMRI) records the temporal dynamics of intrinsic functional networks in the brain. However, existing deep learning methods applied to rs-fMRI either neglect the functional dependency between different brain regions in a network or discard the information in the temporal dynamics of brain activity. To overcome those shortcomings, we propose to formulate functional connectivity networks within the context of spatio-temporal graphs. We train a spatio-temporal graph convolutional network (ST-GCN) on short sub-sequences of the BOLD time series to model the non-stationary nature of functional connectivity. Simultaneously, the model learns the importance of graph edges within ST-GCN to gain insight into the functional connectivities contributing to the prediction. In analyzing the rs-fMRI of the Human Connectome Project (HCP, N = 1,091) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA, N = 773), ST-GCN is significantly more accurate than common approaches in predicting gender and age based on BOLD signals. Furthermore, the brain regions and functional connections significantly contributing to the predictions of our model are important markers according to the neuroscience literature.
View details for DOI 10.1007/978-3-030-59728-3_52
View details for PubMedID 33257918
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Inpainting Cropped Diffusion MRI using Deep Generative Models.
PRedictive Intelligence in MEdicine. PRIME (Workshop)
2020; 12329: 91-100
Abstract
Minor artifacts introduced during image acquisition are often negligible to the human eye, such as a confined field of view resulting in MRI missing the top of the head. This cropping artifact, however, can cause suboptimal processing of the MRI resulting in data omission or decreasing the power of subsequent analyses. We propose to avoid data or quality loss by restoring these missing regions of the head via variational autoencoders (VAE), a deep generative model that has been previously applied to high resolution image reconstruction. Based on diffusion weighted images (DWI) acquired by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), we evaluate the accuracy of inpainting the top of the head by common autoencoder models (U-Net, VQVAE, and VAE-GAN) and a custom model proposed herein called U-VQVAE. Our results show that U-VQVAE not only achieved the highest accuracy, but also resulted in MRI processing producing lower fractional anisotropy (FA) in the supplementary motor area than FA derived from the original MRIs. Lower FA implies that inpainting reduces noise in processing DWI and thus increase the quality of the generated results. The code is available at https://github.com/RdoubleA/DWIinpainting.
View details for DOI 10.1007/978-3-030-59354-4_9
View details for PubMedID 33997866
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Vision-based Estimation of MDS-UPDRS Gait Scores for Assessing Parkinson's Disease Motor Severity.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
2020; 12263: 637–47
Abstract
Parkinson's disease (PD) is a progressive neurological disorder primarily affecting motor function resulting in tremor at rest, rigidity, bradykinesia, and postural instability. The physical severity of PD impairments can be quantified through the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), a widely used clinical rating scale. Accurate and quantitative assessment of disease progression is critical to developing a treatment that slows or stops further advancement of the disease. Prior work has mainly focused on dopamine transport neuroimaging for diagnosis or costly and intrusive wearables evaluating motor impairments. For the first time, we propose a computer vision-based model that observes non-intrusive video recordings of individuals, extracts their 3D body skeletons, tracks them through time, and classifies the movements according to the MDS-UPDRS gait scores. Experimental results show that our proposed method performs significantly better than chance and competing methods with an F 1-score of 0.83 and a balanced accuracy of 81%. This is the first benchmark for classifying PD patients based on MDS-UPDRS gait severity and could be an objective biomarker for disease severity. Our work demonstrates how computer-assisted technologies can be used to non-intrusively monitor patients and their motor impairments. The code is available at https://github.com/mlu355/PD-Motor-Severity-Estimation.
View details for DOI 10.1007/978-3-030-59716-0_61
View details for PubMedID 33103164
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Deep Parametric Mixtures for Modeling the Functional Connectome.
PRedictive Intelligence in MEdicine. PRIME (Workshop)
2020; 12329: 133–43
Abstract
Functional connectivity between brain regions is often estimated by correlating brain activity measured by resting-state fMRI in those regions. The impact of factors (e.g, disorder or substance use) are then modeled by their effects on these correlation matrices in individuals. A crucial step in better understanding their effects on brain function could lie in estimating connectomes, which encode the correlation matrices across subjects. Connectomes are mostly estimated by creating a single average for a specific cohort, which works well for binary factors (such as sex) but is unsuited for continuous ones, such as alcohol consumption. Alternative approaches based on regression methods usually model each pair of regions separately, which generally produces incoherent connectomes as correlations across multiple regions contradict each other. In this work, we address these issues by introducing a deep learning model that predicts connectomes based on factor values. The predictions are defined on a simplex spanned across correlation matrices, whose convex combination guarantees that the deep learning model generates well-formed connectomes. We present an efficient method for creating these simplexes and improve the accuracy of the entire analysis by defining loss functions based on robust norms. We show that our deep learning approach is able to produce accurate models on challenging synthetic data. Furthermore, we apply the approach to the resting-state fMRI scans of 281 subjects to study the effect of sex, alcohol, and HIV on brain function.
View details for DOI 10.1007/978-3-030-59354-4_13
View details for PubMedID 33163995
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Deep Learning Identifies Morphological Determinants of Sex Differences in the Pre-Adolescent Brain.
NeuroImage
2020: 117293
Abstract
The application of data-driven deep learning to identify sex differences in developing brain structures of pre-adolescents has heretofore not been accomplished. Here, the approach identifies sex differences by analyzing the minimally processed MRIs of the first 8,144 participants (age 9 and 10 years) recruited by the Adolescent Brain Cognitive Development (ABCD) study. The identified pattern accounted for confounding factors (i.e., head size, age, puberty development, socioeconomic status) and comprised cerebellar (corpus medullare, lobules III, IV/V, and VI) and subcortical (pallidum, amygdala, hippocampus, parahippocampus, insula, putamen) structures. While these have been individually linked to expressing sex differences, a novel discovery was that their grouping accurately predicted the sex in individual pre-adolescents. Another novelty was relating differences specific to the cerebellum to pubertal development. Finally, we found that reducing the pattern to a single score not only accurately predicted sex but also correlated with cognitive behavior linked to working memory. The predictive power of this score and the constellation of identified brain structures provide evidence for sex differences in pre-adolescent neurodevelopment and may augment understanding of sex-specific vulnerability or resilience to psychiatric disorders and presage sex-linked learning disabilities.
View details for DOI 10.1016/j.neuroimage.2020.117293
View details for PubMedID 32841716
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Effects of age, sex, and puberty on neural efficiency of cognitive and motor control in adolescents
BRAIN IMAGING AND BEHAVIOR
2020; 14 (4): 1089–1107
View details for DOI 10.1007/s11682-019-00075-x
View details for Web of Science ID 000552051500012
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Accelerated aging and motor control deficits are related to regional deformation of central cerebellar white matter in alcohol use disorder
ADDICTION BIOLOGY
2020; 25 (3)
View details for DOI 10.1111/adb.12746
View details for Web of Science ID 000528674100024
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Corrigendum: Graded Cerebellar Lobular Volume Deficits in Adolescents and Young Adults with Fetal Alcohol Spectrum Disorders (FASD).
Cerebral cortex (New York, N.Y. : 1991)
2020
View details for DOI 10.1093/cercor/bhaa091
View details for PubMedID 32249891
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Graded Cerebellar Lobular Volume Deficits in Adolescents and Young Adults with Fetal Alcohol Spectrum Disorders (FASD).
Cerebral cortex (New York, N.Y. : 1991)
2020
Abstract
The extensive prenatal developmental growth period of the cerebellum renders it vulnerable to unhealthy environmental agents, especially alcohol. Fetal alcohol spectrum disorders (FASD) is marked by neurodysmorphology including cerebral and cerebellar volume deficits, but the cerebellar lobular deficit profile has not been delineated. Legacy MRI data of 114 affected and 60 unaffected adolescents and young adults were analyzed for lobular gray matter volume and revealed graded deficits supporting a spectrum of severity. Graded deficits were salient in intracranial volume (ICV), where the fetal alcohol syndrome (FAS) group was smaller than the fetal alcohol effects (FAE) group, which was smaller than the controls. Adjusting for ICV, volume deficits were present in VIIB and VIIIA of the FAE group and were more widespread in FAS and included lobules I, II, IV, V, VI, Crus II, VIIB, and VIIA. Graded deficits (FAS
View details for DOI 10.1093/cercor/bhaa020
View details for PubMedID 32133485
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Regional growth trajectories of cortical myelination in adolescents and young adults: longitudinal validation and functional correlates
BRAIN IMAGING AND BEHAVIOR
2020; 14 (1): 242–66
View details for DOI 10.1007/s11682-018-9980-3
View details for Web of Science ID 000511797100023
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Disturbed sensory physiology underlies poor balance and disrupts activities of daily living in alcohol use disorder.
Addiction biology
2020: e12966
Abstract
Postural stability is a multi-factorial skill maintained implicitly. Components of quiet standing can decline with Alcohol Use Disorder (AUD), cause instability, and disrupt activities of daily living (ADL). To examine how stability factors contribute to ADL and balance, 638 force platform testing sessions measured sway paths acquired during quiet standing in 151 AUD and 96 control men and women, age 25-75. Structural equation (seq) path analysis estimated contributions from age, diagnosis, and sensory perception to sway and measures of ADL and roadside ataxia testing. Whether eyes were open or closed, older AUD and control participants had longer sway paths than younger ones; older men had longer sway paths than older women. Although each sensory ability tested declined with aging, different factor constellations influenced ADL, ataxia scores, or sway path. Seq-path analysis indicated that ADL was strongly dependent on sensory (but not cognitive) systems with sway-path length accounting for upwards of 25% of variance. Within the AUD group, an index of historically-experienced withdrawal symptoms was a common predictor of stability regardless of vision condition. The greatest variance measured by the seq-path model was for predicting platform sway and simple ataxia testing of one-leg standing even though these measures were affected by different predictor variables: strong predictors of one-leg standing were diagnosis and age (R2 = 39.6%-43.2%), whereas strong predictors of sway-path length were sensory factors and withdrawal index (R2 = 22.0%-22.9%). These findings present evidence for appreciating selective factors that contribute to declining postural stability and to liability for compromised quality of life in AUD.
View details for DOI 10.1111/adb.12966
View details for PubMedID 33098738
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Structural and biochemical imaging reveals systemic LPS-induced changes in the rat brain.
Journal of neuroimmunology
2020; 348: 577367
Abstract
Despite mounting evidence for the role of inflammation in Major Depressive Disorder (MDD), in vivo preclinical investigations of inflammation-induced negative affect using whole brain imaging modalities are scarce, precluding a valid model within which to evaluate pharmacological interventions. Here we used an E. coli lipopolysaccharide (LPS)-based model of inflammation-induced depressive signs in rats to explore brain changes using multimodal neuroimaging methods. During the acute phase of the LPS response (2 h post injection), prior to the emergence of a task-quantifiable depressive phenotype, striatal glutamine levels and splenial, retrosplenial, and peri-callosal hippocampal cortex volumes were greater than at baseline. LPS-induced depressive behaviors observed at 24 h, however, occurred concurrently with lower than control levels of striatal glutamine and a reversibility of volume expansion (i.e., shrinkage of splenial, retrosplenial, and peri-callosal hippocampal cortex to baseline volumes). In both striatum and hippocampus at 24 h, mRNA expression in LPS relative to control animals demonstrated alterations in enzymes and transporters regulating glutamine homeostasis. Collectively, the observed behavioral, in vivo structural and metabolic, and mRNA expression alterations suggest a critical role for astrocytic regulation of inflammation-induced depressive behaviors.
View details for DOI 10.1016/j.jneuroim.2020.577367
View details for PubMedID 32866714
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Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls.
Addiction biology
2020: e12914
Abstract
Exogenous causes, such as alcohol use, and endogenous factors, such as temperament and sex, can modulate developmental trajectories of adolescent neurofunctional maturation. We examined how these factors affect sexual dimorphism in brain functional networks in youth drinking below diagnostic threshold for alcohol use disorder (AUD). Based on the 3-year, annually acquired, longitudinal resting-state functional magnetic resonance imaging (MRI) data of 526 adolescents (12-21 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) cohort, developmental trajectories of 23 intrinsic functional networks (IFNs) were analyzed for (1) sexual dimorphism in 259 participants who were no-to-low drinkers throughout this period; (2) sex-alcohol interactions in two age- and sex-matched NCANDA subgroups (N = 76 each), half no-to-low, and half moderate-to-heavy drinkers; and (3) moderating effects of gender-specific alcohol dose effects and a multifactorial impulsivity measure on IFN connectivity in all NCANDA participants. Results showed that sex differences in no-to-low drinkers diminished with age in the inferior-occipital network, yet girls had weaker within-network connectivity than boys in six other networks. Effects of adolescent alcohol use were more pronounced in girls than boys in three IFNs. In particular, girls showed greater within-network connectivity in two motor networks with more alcohol consumption, and these effects were mediated by sensation-seeking only in girls. Our results implied that drinking might attenuate the naturally diminishing sexual differences by disrupting the maturation of network efficiency more severely in girls. The sex-alcohol-dose effect might explain why women are at higher risk of alcohol-related health and psychosocial consequences than men.
View details for DOI 10.1111/adb.12914
View details for PubMedID 32428984
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Multi-modal imaging reveals differential brain volumetric, biochemical, and white matter fiber responsivity to repeated intermittent ethanol vapor exposure in male and female rats.
Neuropharmacology
2020: 108066
Abstract
A generally accepted framework derived predominately from animal models asserts that repeated cycles of chronic intermittent ethanol (EtOH; CIE) exposure cause progressive brain adaptations associated with anxiety and stress that promote voluntary drinking, alcohol dependence, and further brain changes that contribute to the pathogenesis of alcoholism. The current study used CIE exposure via vapor chambers to test the hypothesis that repeated episodes of withdrawals from chronic EtOH would be associated with accrual of brain damage as quantified using in vivo magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS). The initial study group included 16 male (∼325g) and 16 female (∼215g) wild-type Wistar rats exposed to 3 cycles of 1-month in vapor chambers + 1 week of abstinence. Half of each group (n = 8) was given vaporized EtOH to blood alcohol levels approaching 250 mg/dL. Blood and behavior markers were also quantified. There was no evidence for dependence (i.e., increased voluntary EtOH consumption), increased anxiety, or an accumulation of pathology. Neuroimaging brain responses to exposure included increased cerebrospinal fluid (CSF) and decreased gray matter volumes, increased Choline/Creatine, and reduced fimbria-fornix fractional anisotropy (FA) with recovery seen after one or more cycles and effects in female more prominent than in male rats. These results show transient brain integrity changes in response to CIE sufficient to induce acute withdrawal but without evidence for cumulative or escalating damage. Together, the current study suggests that nutrition, age, and sex should be considered when modeling human alcoholism.
View details for DOI 10.1016/j.neuropharm.2020.108066
View details for PubMedID 32240669
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Age differences in brain structural and metabolic responses to binge ethanol exposure in fisher 344 rats.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2020
Abstract
An overarching goal of our research has been to develop a valid animal model of alcoholism with similar imaging phenotypes as those observed in humans with the ultimate objective of assessing the effectiveness of pharmacological agents. In contrast to our findings in humans with alcohol use disorders (AUD), our animal models have not demonstrated enduring brain pathology despite chronic, high ethanol (EtOH) exposure protocols. Relative to healthy controls, older individuals with AUD demonstrate accelerating brain tissue loss with advanced age. Thus, this longitudinally controlled study was conducted in 4-month old (equivalent to ~16-year-old humans) and 17-month old (equivalent to ~45-year-old humans) male and female Fisher 344 rats to test the hypothesis that following equivalent alcohol exposure protocols, older relative to younger would exhibit more brain changes as evaluated using in vivo structural magnetic resonance imaging (MRI) and MR spectroscopy (MRS). At baseline, total brain volume as well as the volumes of each of the three constituent tissue types (i.e., cerebral spinal fluid (CSF), gray matter, white matter) were greater in old relative to young rats. Baseline metabolite levels (except for GSH) were higher in older than younger animals. Effects of binge ethanol (EtOH) exposure on brain volumes and neurometabolites replicated our previous findings in Wistar rats and included ventricular enlargement and reduced MRS-derived creatine levels. Brain changes in response to binge EtOH treatment were more pronounced in young relative to older animals, negating our hypothesis. Additional metabolite changes including low inositol levels in response to high blood alcohol levels suggest a mechanism of reversible osmolarity disturbances due to temporarily altered brain energy metabolism. Higher baseline GSH levels in female than male rats suggest that female rats are perhaps protected against the more pronounced changes in CSF and gray matter volumes observed in male rats due to superior metabolic homeostasis mechanisms.
View details for DOI 10.1038/s41386-020-0744-6
View details for PubMedID 32580206
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Jacobian Mapping Reveals Converging Substrates of Disruption and Repair in Response to Ethanol Exposure and Abstinence in Two Strains of Rats.
Alcoholism, clinical and experimental research
2020
Abstract
In a previous study using Jacobian mapping to evaluate the morphological effects on the brain of binge (4-day) intragastric ethanol (EtOH) on wild-type Wistar rats, we reported reversible thalamic shrinkage and lateral ventricular enlargement, but persistent superior and inferior colliculi shrinkage in response to binge EtOH treatment.Herein, we used similar voxel-based comparisons of Magnetic Resonance Images collected in EtOH-exposed relative to control animals to test the hypothesis that regardless of the intoxication protocol or the rat strain, the hippocampi, thalami, and colliculi would be affected.Two experiments [binge (4-day) intragastric EtOH in Fisher 344 rats and chronic (1-month) vaporized EtOH in Wistar rats] showed similarly affected brain regions including retrosplenial and cingulate cortices, dorsal hippocampi, central and ventroposterior thalami, superior and inferior colliculi, periaqueductal gray, and corpus callosum. While most of these regions showed significant recovery, volumes of the colliculi and periaqueductal gray continued to show response to each proximal alcohol exposure but at diminished levels with repeated exposures.Given the high metabolic rate of these enduringly affected regions, the current findings suggest that EtOH per se may affect cellular respiration leading to brain volume deficits. Further, responsivity greatly diminished likely reflecting neuroadaptation to repeated alcohol exposure. In summary, this unbiased, in vivo based approach demonstrating convergent brain systems responsive to two EtOH exposure protocols in two rat strains highlights regions that warrant further investigation in both animal models of alcoholism and in humans with Alcohol Use Disorder.
View details for DOI 10.1111/acer.14496
View details for PubMedID 33119896
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Pattern of Cerebellar Lobular Volume Deficits in Adolescents and Adults With Fetal Alcohol Effects (FAE) and Fetal Alcohol Syndrome (FAS)
NATURE PUBLISHING GROUP. 2019: 281–82
View details for Web of Science ID 000509665600522
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Confounder-Aware Visualization of ConvNets.
Machine learning in medical imaging. MLMI (Workshop)
2019; 11861: 328–36
Abstract
With recent advances in deep learning, neuroimaging studies increasingly rely on convolutional networks (ConvNets) to predict diagnosis based on MR images. To gain a better understanding of how a disease impacts the brain, the studies visualize the salience maps of the ConvNet highlighting voxels within the brain majorly contributing to the prediction. However, these salience maps are generally confounded, i.e., some salient regions are more predictive of confounding variables (such as age) than the diagnosis. To avoid such misinterpretation, we propose in this paper an approach that aims to visualize confounder-free saliency maps that only highlight voxels predictive of the diagnosis. The approach incorporates univariate statistical tests to identify confounding effects within the intermediate features learned by ConvNet. The influence from the subset of confounded features is then removed by a novel partial back-propagation procedure. We use this two-step approach to visualize confounder-free saliency maps extracted from synthetic and two real datasets. These experiments reveal the potential of our visualization in producing unbiased model-interpretation.
View details for DOI 10.1007/978-3-030-32692-0_38
View details for PubMedID 32549051
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Covariance Shrinkage for Dynamic Functional Connectivity.
Connectomics in neuroImaging : third International Workshop, CNI 2019, held in conjunction with MICCAI 2019, Shenzhen, China, October 13, 2019, Proceedings. CNI (Workshop) (3rd : 2019 : Shenzhen Shi, China)
2019; 11848: 32–41
Abstract
The tracking of dynamic functional connectivity (dFC) states in resting-state fMRI scans aims to reveal how the brain sequentially processes stimuli and thoughts. Despite the recent advances in statistical methods, estimating the high dimensional dFC states from a small number of available time points remains a challenge. This paper shows that the challenge is reduced by linear covariance shrinkage, a statistical method used for the estimation of large covariance matrices from small number of samples. We present a computationally efficient formulation of our approach that scales dFC analysis up to full resolution resting-state fMRI scans. Experiments on synthetic data demonstrate that our approach produces dFC estimates that are closer to the ground-truth than state-of-the-art estimation approaches. When comparing methods on the rs-fMRI scans of 162 subjects, we found that our approach is better at extracting functional networks and capturing differences in rs-fMRI acquisition and diagnosis.
View details for DOI 10.1007/978-3-030-32391-2_4
View details for PubMedID 32924030
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Disturbed Cerebellar Growth Trajectories in Adolescents Who Initiate Alcohol Drinking.
Biological psychiatry
2019
Abstract
BACKGROUND: The cerebellum is a target of alcoholism-related brain damage in adults, yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking.METHODS: Magnetic resonance imaging tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no/low drinking youths age 12 to 21 years at induction into this 5-site, NCANDA (National Consortium on Alcohol and NeuroDevelopment in Adolescence) study. Over the 3- to 4-year longitudinal examination yielding 2043 magnetic resonance imaging scans, 328 youths remained no/low drinkers, whereas 220 initiated substantial drinking after initial neuroimaging.RESULTS: Normal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V and VI, crus II, lobule VIIB, and lobule X declined faster with age in male youths than in female youths, whereas white matter volumes in crus I and crus II and lobules VIIIA and VIIIB expanded faster in female youths than in male youths; cerebrospinal fluid volume expanded faster in most cerebellar regions of male youths than female youths. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated cerebrospinal fluid volumes expansion of anterior lobules relative to youths who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana in alcohol effects on cerebellar gray matter trajectories.CONCLUSIONS: Alcohol use-related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youths who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected by youthful drinking may be vulnerable to age-alcohol interactions in later adulthood.
View details for DOI 10.1016/j.biopsych.2019.08.026
View details for PubMedID 31653477
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Dissociable Contributions of Precuneus and Cerebellum to Subjective and Objective Neuropathy in HIV
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
2019; 14 (3): 436–47
View details for DOI 10.1007/s11481-019-09837-2
View details for Web of Science ID 000484524100009
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Brain-Behavior Relations and Effects of Aging and Common Comorbidities in Alcohol Use Disorder: A Review
NEUROPSYCHOLOGY
2019; 33 (6): 760–80
Abstract
Alcohol use disorder (AUD) is a complex, dynamic condition that waxes and wanes with unhealthy drinking episodes and varies in drinking patterns and effects on brain structure and function with age. Its excessive use renders chronically heavy drinkers vulnerable to direct alcohol toxicity and a variety of comorbidities attributable to nonalcohol drug misuse, viral infections, and accelerated or premature aging. AUD affects widespread brain systems, commonly, frontolimbic, frontostriatal, and frontocerebellar networks.Multimodal assessment using selective neuropsychological testing and whole-brain neuroimaging provides evidence for AUD-related specific brain structure-function relations established with double dissociations. Longitudinal study using noninvasive imaging provides evidence for brain structural and functional improvement with sustained sobriety and further decline with relapse. Functional imaging suggests the possibility that some alcoholics in recovery can compensate for impairment by invoking brain systems typically not used for a target task but that can enable normal-level performance.Evidence for AUD-aging interactions, indicative of accelerated aging, together with increasing alcohol consumption in middle-age and older adults, put aging drinkers at special risk for developing cognitive decline and possibly dementia. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
View details for DOI 10.1037/neu0000557
View details for Web of Science ID 000482569400002
View details for PubMedID 31448945
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CNS Correlates of "Objective" Neuropathy in Alcohol Use Disorder.
Alcoholism, clinical and experimental research
2019
Abstract
BACKGROUND: Among the neurological consequences of alcoholism is peripheral neuropathy. Relative to HIV or diabetes-related neuropathies, neuropathy associated with Alcohol Use Disorders (AUD) is understudied. In both the diabetes and HIV literature, emerging evidence supports a CNS component to peripheral neuropathy.METHODS: In seeking a central substrate for AUD-related neuropathy, the current study was conducted in 154 individuals with AUD (43 women, ages 21-74) and 99 healthy controls (41 women, ages 21-77) and explored subjective symptoms (self-report) and objective signs (perception of vibration, deep tendon ankle reflex, position sense, 2-point discrimination) of neuropathy separately. In addition to regional brain volumes, risk factors for AUD-related neuropathy, including age, sex, total lifetime ethanol consumed, nutritional indices (i.e., thiamine, folate), and measures of liver integrity (i.e., gamma-glutamyl-transferase) were evaluated.RESULTS: The AUD group described more subjective symptoms of neuropathy and were more frequently impaired on bilateral perception of vibration. From 5 correlates, the number of AUD-related seizures was most significantly associated with subjective symptoms of neuropathy. There were 15 correlates of impaired perception of vibration among the AUD participants: of these, age and volume of frontal precentral cortex were the most robust predictors.CONCLUSIONS: This study supports CNS involvement in objective signs of neuropathy in AUD. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/acer.14162
View details for PubMedID 31386216
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Cognitive and Motor Impairment Severity Related to Signs of Subclinical Wernicke's Encephalopathy in HIV Infection
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
2019; 81 (3): 345–54
View details for DOI 10.1097/QAI.0000000000002043
View details for Web of Science ID 000480774900019
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Prospective Study of Adolescents Reveals Disturbed Trajectories of Frontal Cortical and Cerebellar Volumes Following Initiation of Drinking
ELSEVIER SCIENCE INC. 2019: S12
View details for DOI 10.1016/j.biopsych.2019.03.043
View details for Web of Science ID 000472661000030
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Cognitive and Motor Impairment Severity Related to Signs of Subclinical Wernicke's Encephalopathy in HIV Infection.
Journal of acquired immune deficiency syndromes (1999)
2019
Abstract
BACKGROUND: Wernicke's encephalopathy (WE) is a neurological condition resulting from thiamine deficiency. Although commonly associated with alcoholism, non-alcoholic WE has been described in individuals with Human Immunodeficiency Virus (HIV) infection, but subclinical WE may be underdiagnosed. The current study questioned whether presence of subclinical WE signs underlies cognitive and motor deficits in HIV individuals as observed in alcoholism.SETTING: 56 HIV positive individuals (HIV+) and 53 HIV negative controls (HIV-) were assessed on 6 cognitive and motor domains: attention/working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function.METHODS: Based on a rating scheme by Caine et al, HIV+ individuals were categorized by subclinical WE risk factors (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state). Performance was expressed as age- and education-corrected Z-scores standardized on controls.RESULTS: Sorting by Caine criteria yielded 20 HIV+ as Caine 0 (i.e., meeting no criteria), 22 as Caine 1 (i.e., meeting one criterion), and 14 as Caine 2 (i.e., meeting two criteria). Comparison among HIV+ Caine subgroups revealed a graded effect: Caine 0 performed at control levels, Caine 1 showed mild to moderate deficits on some domains, and Caine 2 showed the most severe deficits on each domain.CONCLUSION: This graded severity pattern of performance among Caine subgroups suggests that signs of subclinical WE can partly explain the heterogeneity in HIV-related cognitive and motor impairment. This study highlights the utility of Caine criteria in identifying potential causes of HIV-related neurocognitive disorders and has implications for disease management.
View details for PubMedID 30958387
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Accelerated aging and motor control deficits are related to regional deformation of central cerebellar white matter in alcohol use disorder.
Addiction biology
2019
Abstract
The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1-weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248d) and 128 age- and sex-matched control participants; subsets of these participants completed motor testing. We identified an AUD-related volume deficit and accelerated aging in the total corpus medullare. Novel deformation-based surface morphometry revealed regional shrinkage of surfaces adjacent to lobules I-V, lobule IX, and vermian lobule X. In addition, accelerated aging was detected in the regional surface areas adjacent to lobules I-V, lobule VI, lobule VIIB, and lobules VIII, IX, and X. Sex differences were not identified for any measure. For both volume-based and surface-based analyses, poorer performance in gait and balance, manual dexterity, and grip strength were linked to greater regional white matter structural deficits. Our results suggest that local deformation of the corpus medullare has the potential of identifying structurally and functionally segregated networks affected in AUD.
View details for PubMedID 30932270
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Effects of age, sex, and puberty on neural efficiency of cognitive and motor control in adolescents.
Brain imaging and behavior
2019
Abstract
Critical changes in adolescence involve brain cognitive maturation of inhibitory control processes that are essential for a myriad of adult functions. Cognitive control advances into adulthood as there is more flexible integration of component processes, including inhibitory control of conflicting information, overwriting inappropriate response tendencies, and amplifying relevant responses for accurate execution. Using a modified Stroop task with fMRI, we investigated the effects of age, sex, and puberty on brain functional correlates of cognitive and motor control in 87 boys and 91 girls across the adolescent age range. Results revealed dissociable brain systems for cognitive and motor control processes, whereby adolescents flexibly adapted neural responses to control demands. Specifically, when response repetitions facilitated planning-based action selection, frontoparietal-insular regions associated with cognitive control operations were less activated, whereas cortical-pallidal-cerebellar motor regions associated with motor skill acquisition, were more activated. Attenuated middle cingulate cortex activation occurred with older adolescent age for both motor control and cognitive control with automaticity from repetition learning. Sexual dimorphism for control operations occurred in extrastriate cortices involved in visuo-attentional selection: While boys enhanced extrastriate selection processes for motor control, girls activated these regions more for cognitive control. These sex differences were attenuated with more advanced pubertal stage. Together, our findings show that brain cognitive and motor control processes are segregated, demand-specific, more efficient in older adolescents, and differ between sexes relative to pubertal development. Our findings advance our understanding of how distributed brain activity and the neurodevelopment of automaticity enhances cognitive and motor control ability in adolescence.
View details for PubMedID 30903550
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Hippocampal subfield CA2+3 exhibits accelerated aging in Alcohol Use Disorder: A preliminary study.
NeuroImage. Clinical
2019; 22: 101764
Abstract
The profile of brain structural dysmorphology of individuals with Alcohol Use Disorders (AUD) involves disruption of the limbic system. In vivo imaging studies report hippocampal volume loss in AUD relative to controls, but only recently has it been possible to articulate different regions of this complex structure. Volumetric analysis of hippocampal regions rather than total hippocampal volume may augment differentiation of disease processes. For example, damage to hippocampal subfield cornu ammonis 1 (CA1) is often reported in Alzheimer's disease (AD), whereas deficits in CA4/dentate gyrus are described in response to stress and trauma. Two previous studies explored the effects of chronic alcohol use on hippocampal subfields: one reported smaller volume of the CA2+3 in alcohol-dependent subjects relative to controls, associated with years of alcohol consumption; the other, smaller volumes of presubiculum, subiculum, and fimbria in alcohol-dependent relative to control men. The current study, conducted in 24 adults with DSM5-diagnosed AUD (7 women, 53.7 ± 8.8) and 20 controls (7 women, 54.1 ± 9.3), is the first to use FreeSurfer 6.0, which provides state-of-the art hippocampal parcellation, to explore the sensitivity of hippocampal sufields to alcoholism. T1- and T2- images were collected on a GE MR750 system with a 32-channel Nova head coil. FreeSurfer 6.0 hippocampal subfield analysis produced 12 subfields: parasubiculum; presubiculum; subiculum; CA1; CA2+3; CA4; GC-ML-DG (Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)); molecular layer; hippocampus-amygdala-transition-area (HATA); fimbria; hippocampal tail; hippocampal fissure; and whole volume for left and right hippocampi. A comprehensive battery of neuropsychological tests comprising attention, memory and learning, visuospatial abilities, and executive functions was administered. Multiple regression analyses of raw volumetric data for each subfields by group, age, sex, hemisphere, and supratentorial volume (svol) showed significant effects of svol (p < .04) on nearly all structures (excluding tail and fissure). Volumes corrected for svol showed effects of age (fimbria, fissure) and group (subiculum, CA1, CA4, GC-ML-DG, HATA, fimbria); CA2+3 showed a diagnosis-by-age interaction indicating older AUD individuals had a smaller volume than would be expected for their age. There were no selective relations between hippocampal subfields and performance on neuropsychological tests, likely due to lack of statistical power. The current results concur with the previous study identifying CA2+3 as sensitive to alcoholism, extend them by identifying an alcoholism-age interaction, and suggest an imaging phenotype distinguishing AUD from AD and stress/trauma.
View details for PubMedID 30904825
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Novel Machine Learning Identifies Brain Patterns Distinguishing Diagnostic Membership of Human Immunodeficiency Virus, Alcoholism, and Their Comorbidity of Individuals.
Biological psychiatry. Cognitive neuroscience and neuroimaging
2019
Abstract
The incidence of alcohol use disorder (AUD) in human immunodeficiency virus (HIV) infection is twice that of the rest of the population. This study documents complex radiologically identified, neuroanatomical effects of AUD+HIV comorbidity by identifying structural brain systems that predicted diagnosis on an individual basis. Applying novel machine learning analysis to 549 participants (199 control subjects, 222 with AUD, 68 with HIV, 60 with AUD+HIV), 298 magnetic resonance imaging brain measurements were automatically reduced to small subsets per group. Significance of each diagnostic pattern was inferred from its accuracy in predicting diagnosis and performance on six cognitive measures. While all three diagnostic patterns predicted the learning and memory score, the AUD+HIV pattern was the largest and had the highest predication accuracy (78.1%). Providing a roadmap for analyzing large, multimodal datasets, the machine learning analysis revealed imaging phenotypes that predicted diagnostic membership of magnetic resonance imaging scans of individuals with AUD, HIV, and their comorbidity.
View details for DOI 10.1016/j.bpsc.2019.02.003
View details for PubMedID 30982583
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Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism
ADDICTION BIOLOGY
2019; 24 (2): 290–302
View details for DOI 10.1111/adb.12584
View details for Web of Science ID 000458437000012
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Longitudinally consistent estimates of intrinsic functional networks.
Human brain mapping
2019
Abstract
Increasing numbers of neuroimaging studies are acquiring data to examine changes in brain architecture by investigating intrinsic functional networks (IFN) from longitudinal resting-state functional MRI (rs-fMRI). At the subject level, these IFNs are determined by cross-sectional procedures, which neglect intra-subject dependencies and result in suboptimal estimates of the networks. Here, a novel longitudinal approach simultaneously extracts subject-specific IFNs across multiple visits by explicitly modeling functional brain development as an essential context for seeking change. On data generated by an innovative simulation based on real rs-fMRI, the method was more accurate in estimating subject-specific IFNs than cross-sectional approaches. Furthermore, only group-analysis based on longitudinally consistent estimates identified significant developmental effects within IFNs of 246 adolescents from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. The findings were confirmed by the cross-sectional estimates when the corresponding group analysis was confined to the developmental effects. Those effects also converged with current concepts of neurodevelopment.
View details for DOI 10.1002/hbm.24541
View details for PubMedID 30806009
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Dissociable Contributions of Precuneus and Cerebellum to Subjective and Objective Neuropathy in HIV.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
2019
Abstract
Neuropathy, typically diagnosed by the presence of either symptoms or signs of peripheral nerve dysfunction, remains a frequently reported complication in the antiretroviral (ART)-treated HIV population. This study was conducted in 109 healthy controls and 57 HIV-infected individuals to investigate CNS regions associated with neuropathy. An index of objective neuropathy was computed based on 4 measures: deep tendon ankle reflex, vibration sense (great toes), position sense (great toes), and 2-point discrimination (feet). Subjective neuropathy (self-report of pain, aching, or burning; pins and needles; or numbness in legs or feet) was also evaluated. Structural MRI data were available for 126/166 cases. The HIV relative to the healthy control group was impaired on all 4 signs of neuropathy. Within the HIV group, an objective neuropathy index of 1 (bilateral impairment on 1 measure) or 2 (bilateral impairment on at least 2/4 measures) was associated with older age and a smaller volume of the cerebellar vermis. Moderate to severe symptoms of neuropathy were associated with more depressive symptoms, reduced quality of life, and a smaller volume of the parietal precuneus. This study is consistent with the recent contention that ART-treated HIV-related neuropathy has a CNS component. Distinguishing subjective symptoms from objective signs of neuropathy allowed for a dissociation between the precuneus, a brain region involved in conscious information processing and the vermis, involved in fine tuning of limb movements. Graphical Abstract In HIV patients, objective signs of neuropathy correlated with smaller cerebellar vermis (red) volumes whereas subjective symptoms of neuropathy were associated with smaller precuneus (blue) volumes.
View details for PubMedID 30741374
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Sensitivity of ventrolateral posterior thalamic nucleus to back pain in alcoholism and CD4 nadir in HIV.
Human brain mapping
2019
Abstract
Volumes of thalamic nuclei are differentially affected by disease-related processes including alcoholism and human immunodeficiency virus (HIV) infection. This MRI study included 41 individuals diagnosed with alcohol use disorders (AUD, 12 women), 17 individuals infected with HIV (eight women), and 49 healthy controls (24 women) aged 39 to 75 years. A specialized, high-resolution acquisition protocol enabled parcellation of five thalamic nuclei: anterior [anterior ventral (AV)], posterior [pulvinar (Pul)], medial [mediodorsal (MD)], and ventral [including ventral lateral posterior (VLp) and ventral posterior lateral (VPl)]. An omnibus mixed-model approach solving for volume considered the "fixed effects" of nuclei, diagnosis, and their interaction while covarying for hemisphere, sex, age, and supratentorial volume (svol). The volume by diagnosis interaction term was significant; the effects of hemisphere and sex were negligible. Follow-up mixed-model tests thus evaluated the combined (left + right) volume of each nucleus separately for effects of diagnosis while controlling for age and svol. Only the VLp showed diagnoses effects and was smaller in the AUD (p = .04) and HIV (p = .0003) groups relative to the control group. In the AUD group, chronic back pain (p = .008) and impaired deep tendon ankle reflex (p = .0005) were associated with smaller VLp volume. In the HIV group, lower CD4 nadir (p = .008) was associated with smaller VLp volume. These results suggest that the VLp is differentially sensitive to disease processes associated with AUD and HIV.
View details for DOI 10.1002/hbm.24880
View details for PubMedID 31785046
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Variational Autoencoder with Truncated Mixture of Gaussians for Functional Connectivity Analysis
SPRINGER INTERNATIONAL PUBLISHING AG. 2019: 867–79
View details for DOI 10.1007/978-3-030-20351-1_68
View details for Web of Science ID 000493380900068
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Convergence of three parcellation approaches demonstrating cerebellar lobule volume deficits in Alcohol Use Disorder.
NeuroImage. Clinical
2019; 24: 101974
Abstract
Recent advances in robust and reliable methods of MRI-derived cerebellar lobule parcellation volumetry present the opportunity to assess effects of Alcohol Use Disorder (AUD) on selective cerebellar lobules and relations with indices of nutrition and motor functions. In pursuit of this opportunity, we analyzed high-resolution MRI data acquired in 24 individuals with AUD and 20 age- and sex-matched controls with a 32-channel head coil using three different atlases: the online automated analysis pipeline volBrain Ceres, SUIT, and the Johns Hopkins atlas. Participants had also completed gait and balance examination and hematological analysis of nutritional and liver status, enabling testing of functional meaningfulness of each cerebellar parcellation scheme. Compared with controls, each quantification approach yielded similar patterns of group differences in regional volumes: All three approaches identified AUD-related deficits in total tissue and total gray matter, but only Ceres identified a total white matter volume deficit. Convergent volume differences occurred in lobules I-V, Crus I, VIIIB, and IX. Coefficients of variation (CVs) were <20% for 46 of 56 regions measured and in general were graded: Ceres
View details for DOI 10.1016/j.nicl.2019.101974
View details for PubMedID 31419768
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Cognitive impairment severity in relation to signs of subclinical Wernicke's encephalopathy in HIV and alcoholism comorbidity.
AIDS (London, England)
2019
Abstract
The comorbidity of Human Immunodeficiency Virus (HIV) infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy (WE), a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical WE signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC).61 HIV+ALC individuals and 59 controls were assessed on attention and working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function.Using Caine criteria (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state), HIV+ALC individuals were classified by subclinical WE risk factors.Signs of subclinical WE were present in 20% of the HIV+ALC participants. For attention/working memory, delayed memory, and upper limb motor function, HIV+ALCCaine 2+ (i.e., meeting two or three criteria) demonstrated the most severe deficits, scoring lower than HIV+ALC Caine 1 (i.e., meeting one criterion), HIV+ALC Caine 0 (i.e., meeting no criteria), and controls.The high prevalence of subclinical signs of WE and relevance to performance indicate that this condition should be considered in assessment of HIV-infected individuals, especially when alcoholism comorbidity is known or suspected. Above and beyond clinical factors such as depression, alcoholism and HIV disease-related variables, AIDS, hepatitis C and drug history known to mediate neuropsychological performance, subclinical WE signs could partly explain the heterogeneity in patterns and severity of cognitive and motor impairments in HIV-infected individuals with alcoholism comorbidity.
View details for DOI 10.1097/QAD.0000000000002428
View details for PubMedID 31725430
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Hippocampal subfield CA2+3 exhibits accelerated aging in Alcohol Use Disorder: A preliminary study
NEUROIMAGE-CLINICAL
2019; 22
View details for DOI 10.1016/j.nicl.2019.101764
View details for Web of Science ID 000470123000082
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Longitudinally consistent estimates of intrinsic functional networks
Human Brain Mapping
2019
View details for DOI 10.1002/hbm.24541
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Relations between cognitive and motor deficits and regional brain volumes in individuals with alcoholism.
Brain structure & function
2019
Abstract
Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypothesis that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.
View details for DOI 10.1007/s00429-019-01894-w
View details for PubMedID 31161472
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Jacobian Maps Reveal Under-reported Brain Regions Sensitive to Extreme Binge Ethanol Intoxication in the Rat
FRONTIERS IN NEUROANATOMY
2018; 12
View details for DOI 10.3389/fnana.2018.00108
View details for Web of Science ID 000452849300001
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Jacobian Maps Reveal Under-reported Brain Regions Sensitive to Extreme Binge Ethanol Intoxication in the Rat.
Frontiers in neuroanatomy
2018; 12: 108
Abstract
Individuals aged 12-20 years drink 11% of all alcohol consumed in the United States with more than 90% consumed in the form of binge drinking. Early onset alcohol use is a strong predictor of future alcohol dependence. The study of the effects of excessive alcohol use on the human brain is hampered by limited information regarding the quantity and frequency of exposure to alcohol. Animal models can control for age at alcohol exposure onset and enable isolation of neural substrates of exposure to different patterns and quantities of ethanol (EtOH). As with humans, a frequently used binge exposure model is thought to produce dependence and affect predominantly corticolimbic brain regions. in vivo neuroimaging enables animals models to be examined longitudinally, allowing for each animal to serve as its own control. Accordingly, we conducted 3 magnetic resonance imaging (MRI) sessions (baseline, binge, recovery) to track structure throughout the brains of wild type Wistar rats to test the hypothesis that binge EtOH exposure affects specific brain regions in addition to corticolimbic circuitry. Voxel-based comparisons of 13 EtOH- vs. 12 water- exposed animals identified significant thalamic shrinkage and lateral ventricular enlargement as occurring with EtOH exposure, but recovering with a week of abstinence. By contrast, pretectal nuclei and superior and inferior colliculi shrank in response to binge EtOH treatment but did not recover with abstinence. These results identify brainstem structures that have been relatively underreported but are relevant for localizing neurocircuitry relevant to the dynamic course of alcoholism.
View details for DOI 10.3389/fnana.2018.00108
View details for PubMedID 30618652
View details for PubMedCentralID PMC6297262
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Chained regularization for identifying brain patterns specific to HIV infection
NEUROIMAGE
2018; 183: 425–37
View details for DOI 10.1016/j.neuroimage.2018.08.022
View details for Web of Science ID 000447750200038
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Distribution of brain iron accrual in adolescence: Evidence from cross-sectional and longitudinal analysis.
Human brain mapping
2018
Abstract
To track iron accumulation and location in the brain across adolescence, we repurposed diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) data acquired in 513 adolescents and validated iron estimates with quantitative susceptibility mapping (QSM) in 104 of these subjects. DTI and fMRI data were acquired longitudinally over 1year in 245 male and 268 female, no-to-low alcohol-consuming adolescents (12-21 years at baseline) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. Brain region average signal values were calculated for susceptibility to nonheme iron deposition: pallidum, putamen, dentate nucleus, red nucleus, and substantia nigra. To estimate nonheme iron, the corpus callosum signal (robust to iron effects) was divided by regional signals to generate estimated R2 (edwR2 for DTI) and R2 * (eR2 * for fMRI). Longitudinal iron deposition was measured using the normalized signal change across time for each subject. Validation using baseline QSM, derived from susceptibility-weighted imaging, was performed on 46 male and 58 female participants. Normalized iron deposition estimates from DTI and fMRI correlated with age in most regions; both estimates indicated less iron in boys than girls. QSM results correlated highly with DTI and fMRI results (adjusted R2 = 0.643 for DTI, 0.578 for fMRI). Cross-sectional and longitudinal analyses indicated an initial rapid increase in iron, notably in the putamen and red nucleus, that slowed with age. DTI and fMRI data can be repurposed for identifying regional brain iron deposition in developing adolescents as validated with high correspondence with QSM.
View details for PubMedID 30496644
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Regional growth trajectories of cortical myelination in adolescents and young adults: longitudinal validation and functional correlates.
Brain imaging and behavior
2018
Abstract
Adolescence is a time of continued cognitive and emotional evolution occurring with continuing brain development involving synaptic pruning and cortical myelination. The hypothesis of this study is that heavy myelination occurs in cortical regions with relatively direct, predetermined circuitry supporting unimodal sensory or motor functions and shows a steep developmental slope during adolescence (12-21years) until young adulthood (22-35years) when further myelination decelerates. By contrast, light myelination occurs in regions with highly plastic circuitry supporting complex functions and follows a delayed developmental trajectory. In support of this hypothesis, cortical myelin content was estimated and harmonized across publicly available datasets provided by the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) and the Human Connectome Project (HCP). The cross-sectional analysis of 226 no-to-low alcohol drinking NCANDA adolescents revealed relatively steeper age-dependent trajectories of myelin growth in unimodal primary motor cortex and flatter age-dependent trajectories in multimodal mid/posterior cingulate cortices. This pattern of continued myelination showed smaller gains when the same analyses were performed on 686 young adults of the HCP cohort free of neuropsychiatric diagnoses. Critically, a predicted correlation between a motor task and myelin content in motor or cingulate cortices was found in the NCANDA adolescents, supporting the functional relevance of this imaging neurometric. Furthermore, the regional trajectory slopes were confirmed by performing longitudinally consistent analysis of cortical myelin. In conclusion, coordination of myelin content and circuit complexity continues to develop throughout adolescence, contributes to performance maturation, and may represent active cortical development climaxing in young adulthood.
View details for PubMedID 30406353
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Chained regularization for identifying brain patterns specific to HIV infection.
NeuroImage
2018
Abstract
Human Immunodeficiency Virus (HIV) infection continues to have major adverse public health and clinical consequences despite the effectiveness of combination Antiretroviral Therapy (cART) in reducing HIV viral load and improving immune function. As successfully treated individuals with HIV infection age, their cognition declines faster than reported for normal aging. This phenomenon underlines the importance of improving long-term care, which requires better understanding of the impact of HIV on the brain. In this paper, automated identification of patients and brain regions affected by HIV infection are modeled as a classification problem, whose solution is determined in two steps within our proposed Chained-Regularization framework. The first step focuses on selecting the HIV pattern (i.e., the most informative constellation of brain region measurements for distinguishing HIV infected subjects from healthy controls) by constraining the search for the optimal parameter setting of the classifier via group sparsity (ℓ2,1-norm). The second step improves classification accuracy by constraining the parameterization with respect to the selected measurements and the Euclidean regularization (ℓ2-norm). When applied to the cortical and subcortical structural Magnetic Resonance Images (MRI) measurements of 65 controls and 65 HIV infected individuals, this approach is more accurate in distinguishing the two cohorts than more common models. Finally, the brain regions of the identified HIV pattern concur with the HIV literature that uses traditional group analysis models.
View details for PubMedID 30138676
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Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection.
Biological psychiatry. Cognitive neuroscience and neuroimaging
2018
Abstract
BACKGROUND: Life expectancy of successfully treated human immunodeficiency virus (HIV)-infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures.METHODS: This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects. We tested 1) whether localized brain regions in HIV-infected individuals exhibited accelerated aging, or alternatively, nonaccelerated premature aging deficits; and 2) the extent to which alcohol or substance dependence or HCV coinfection altered brain aging trajectories.RESULTS: The HIV-infected cohort exhibited steeper declining volume trajectories than control subjects, consistently in the frontal cortex. Nonaccelerated volume deficits occurred in the temporal, parietal, insular, and cingulate regions of all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV coinfection exacerbated HIV-related volume deficits. Accelerated age interactions in frontal and posterior parietal volumes endured in HIV-infected individuals free of alcohol or substance dependence and HCV infection comorbidities. Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans Aging Cohort Study indices correlated with smaller regional brain volumes in the HIV-infected individuals without alcohol dependence and alcohol-dependent groups.CONCLUSIONS: HIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.
View details for PubMedID 30093343
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Alcohol use effects on adolescent brain development revealed by simultaneously removing confounding factors, identifying morphometric patterns, and classifying individuals
SCIENTIFIC REPORTS
2018; 8: 8297
Abstract
Group analysis of brain magnetic resonance imaging (MRI) metrics frequently employs generalized additive models (GAM) to remove contributions of confounding factors before identifying cohort specific characteristics. For example, the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) used such an approach to identify effects of alcohol misuse on the developing brain. Here, we hypothesized that considering confounding factors before group analysis removes information relevant for distinguishing adolescents with drinking history from those without. To test this hypothesis, we introduce a machine-learning model that identifies cohort-specific, neuromorphometric patterns by simultaneously training a GAM and generic classifier on macrostructural MRI and microstructural diffusion tensor imaging (DTI) metrics and compare it to more traditional group analysis and machine-learning approaches. Using a baseline NCANDA MR dataset (N = 705), the proposed machine learning approach identified a pattern of eight brain regions unique to adolescents who misuse alcohol. Classifying high-drinking adolescents was more accurate with that pattern than using regions identified with alternative approaches. The findings of the joint model approach thus were (1) impartial to confounding factors; (2) relevant to drinking behaviors; and (3) in concurrence with the alcohol literature.
View details for PubMedID 29844507
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The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise
JAMA PSYCHIATRY
2018; 75 (5): 474–83
Abstract
The prevalence of alcohol misuse increased substantially over a decade in adults, particularly in those aged 65 years or older. Ramifications for brain structural integrity are significant, especially in older adults.To combine cross-sectional, longitudinal data to test age-alcoholism interactions and examine the association between prevalent comorbidities (drug dependence and hepatitis C virus [HCV] infection) and cortical volume deficits in alcohol dependence.During 14 years, 826 structural magnetic resonance images were acquired in 222 individuals with alcohol dependence and 199 age-matched control participants (aged 25-75 years at initial study), parcellated with a common atlas, and adjusted for brain volume. Longitudinal data were available on 116 participants with alcoholism and 96 control participants. DSM-IV criteria determined alcohol and drug diagnoses; serology testing determined HCV status. The study was conducted at SRI International and Stanford University School of Medicine from April 11, 2003, to March 3, 2017.Magnetic resonance imaging-derived regional cortical volumes corrected for supratentorial volume and sex.Of the 222 participants with alcoholism, 156 (70.3%) were men; mean (SD) age was 48.0 (10.0) years; the mean age for the 199 control participants was 47.6 (14.0) years. Participants with alcohol dependence had volume deficits in frontal (t = -5.732, P < .001), temporal (t = -3.151, P = .002), parietal (t = -5.063, P < .001), cingulate (t = -3.170, P = .002), and insular (t = -4.920, P < .001) cortices; deficits were prominent in frontal subregions and were not sex dependent. Accelerated aging occurred in frontal cortex (t = -3.019, P < .02) and precentral (t = -2.691, P < .05) and superior gyri (t = -2.763, P < .05) and could not be attributed to the amount of alcohol consumed, which was greater in younger-onset than older-onset participants with alcoholism (t = 6.1191, P < .001). Given the high drug-dependence incidence (54.5%) in the alcoholism group, analysis examined drug subgroups (cocaine, cannabis, amphetamines, opiates) compared with drug-dependence-free alcoholism and control groups. Although the alcohol plus cocaine (t = -2.310, P = .04) and alcohol plus opiate (t = -2.424, P = .04) groups had smaller frontal volumes than the drug-dependence-free alcoholism group, deficits in precentral (t = -2.575, P = .01), supplementary motor (t = -2.532, P = .01), and medial (t = -2.800, P = .01) volumes endured in drug-dependence-free participants with alcoholism compared with control participants. Those with HCV infection had greater deficits than those without HCV infection in frontal (t = 3.468, P = .01), precentral (t = 2.513, P = .03), superior (t = 2.533, P = .03), and orbital (t = 2.506, P = .03) volumes, yet total frontal (t = 2.660, P = .02), insular (t = 3.526, P = .003), parietal (t = 2.414, P = .03), temporal (t = 3.221, P = .005), and precentral (t = 3.180, P = .01) volume deficits persisted in the uninfected participants with alcoholism compared with control participants with known HCV status.Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life.
View details for PubMedID 29541774
View details for PubMedCentralID PMC5875381
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CNS CORRELATES OF HIV-ASSOCIATED PERIPHERAL NEUROPATHY AND POSTURAL INSTABILITY
SPRINGER. 2018: S94
View details for Web of Science ID 000434755400325
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CNS CORRELATES OF HIV-ASSOCIATED PERIPHERAL NEUROPATHY AND POSTURAL INSTABILITY
SPRINGER. 2018: S94
View details for Web of Science ID 000429149100325
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Altered Brain Developmental Trajectories in Adolescents After Initiating Drinking.
The American journal of psychiatry
2018; 175 (4): 370–80
Abstract
OBJECTIVE: The authors sought evidence for altered adolescent brain growth trajectory associated with moderate and heavy alcohol use in a large national, multisite, prospective study of adolescents before and after initiation of appreciable alcohol use.METHOD: This study examined 483 adolescents (ages 12-21) before initiation of drinking and 1 and 2 years later. At the 2-year assessment, 356 participants continued to meet the study's no/low alcohol consumption entry criteria, 65 had initiated moderate drinking, and 62 had initiated heavy drinking. MRI was used to quantify regional cortical and white matter volumes. Percent change per year (slopes) in adolescents who continued to meet no/low criteria served as developmental control trajectories against which to compare those who initiated moderate or heavy drinking.RESULTS: In no/low drinkers, gray matter volume declined throughout adolescence and slowed in many regions in later adolescence. Complementing gray matter declines, white matter regions grew at faster rates at younger ages and slowed toward young adulthood. Youths who initiated heavy drinking exhibited an accelerated frontal cortical gray matter trajectory, divergent from the norm. Although significant effects on trajectories were not observed in moderate drinkers, their intermediate position between no/low and heavy drinkers suggests a dose effect. Neither marijuana co-use nor baseline volumes contributed significantly to the alcohol effect.CONCLUSIONS: Initiation of drinking during adolescence, with or without marijuana co-use, disordered normal brain growth trajectories. Factors possibly contributing to abnormal cortical volume trajectories include peak consumption in the past year and family history of alcoholism.
View details for PubMedID 29084454
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Aberrant blood-oxygen-level-dependent signal oscillations across frequency bands characterize the alcoholic brain
ADDICTION BIOLOGY
2018; 23 (2): 824–35
Abstract
Chronic alcoholism is associated with widespread regional differences from controls in brain activity and connectivity dynamics measured by blood-oxygen-level-dependent (BOLD) signals. Identification of alcoholism-related neurofunctional power dynamics using functional magnetic resonance imaging (fMRI) that relate to cognition and behavior may serve as biomarkers of alcoholism. Previously, resting-state fMRI studies examined BOLD signals at a single low-frequency (LF) bandwidth. BOLD signals, however, oscillate systematically at different frequencies and are organized in a resting brain where LF oscillation facilitates long-distance communication between regions across cortical regions, whereas high-frequency (HF) oscillation occurs in closely localized, subcortical areas. Using a frequency power quantification approach, we investigated whether the organization of BOLD signal oscillations across all measured frequency bandwidths is altered in alcoholism and relates to cognitive performance. Frequency-dependent oscillation power differences between 56 sober alcoholics and 56 healthy controls occurred for all frequency bands. Alcoholics exhibited greater frequency oscillation power in the orbitofrontal cortex and less power in the posterior insula within the HF bandwidth than controls. Aberrant orbitofrontal HF power was associated with poorer memory performance and slower psychomotor speed in alcoholics. Middle-frequency and LF power proved sensitive in detecting altered frequency oscillation dynamics in parietal and postcentral cortical regions of alcoholics. This study is novel in identifying alcohol-related differences in BOLD oscillation power of the full fMRI frequency bandwidth. Specifically, HF power aberrations were associated with poorer cognitive functioning in alcoholism and may serve as a biomarker for identifying neural targets for repair.
View details for PubMedID 28699704
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The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence
BRAIN STRUCTURE & FUNCTION
2018; 223 (2): 669–85
Abstract
During the course of adolescence, reductions occur in cortical thickness and gray matter (GM) volume, along with a 65% reduction in slow-wave (delta) activity during sleep (SWA) but empirical data linking these structural brain and functional sleep differences, is lacking. Here, we investigated specifically whether age-related differences in cortical thickness and GM volume and cortical thickness accounted for the typical age-related difference in slow-wave (delta) activity (SWA) during sleep. 132 healthy participants (age 12-21 years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study were included in this cross-sectional analysis of baseline polysomnographic, electroencephalographic, and magnetic resonance imaging data. By applying mediation models, we identified a large, direct effect of age on SWA in adolescents, which explained 45% of the variance in ultra-SWA (0.3-1 Hz) and 52% of the variance in delta-SWA (1 to <4 Hz), where SWA was lower in older adolescents, as has been reported previously. In addition, we provide evidence that the structure of several, predominantly frontal, and parietal brain regions, partially mediated this direct age effect, models including measures of brain structure explained an additional 3-9% of the variance in ultra-SWA and 4-5% of the variance in delta-SWA, with no differences between sexes. Replacing age with pubertal status in models produced similar results. As reductions in GM volume and cortical thickness likely indicate synaptic pruning and myelination, these results suggest that diminished SWA in older, more mature adolescents may largely be driven by such processes within a number of frontal and parietal brain regions.
View details for PubMedID 28913599
View details for PubMedCentralID PMC5828920
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Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism.
Addiction biology
2017
Abstract
Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n=96) and a normal comparison group (n=41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non-mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non-mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.
View details for PubMedID 29243370
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Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use.
Frontiers in behavioral neuroscience
2017; 11: 223
Abstract
During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD) risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF), cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21) were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use.
View details for DOI 10.3389/fnbeh.2017.00223
View details for PubMedID 29180956
View details for PubMedCentralID PMC5694208
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Peripheral TNF alpha Levels Correlate With Hippocampal Volume in Alcoholism but not in HIV Infection
NATURE PUBLISHING GROUP. 2017: S277–S278
View details for Web of Science ID 000416846301257
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Alcohol's Effects on the Brain: Neuroimaging Results in Humans and Animal Models.
Alcohol research : current reviews
2017; 38 (2): 183-206
Abstract
Brain imaging technology has allowed researchers to conduct rigorous studies of the dynamic course of alcoholism through periods of drinking, sobriety, and relapse and to gain insights into the effects of chronic alcoholism on the human brain. Magnetic resonance imaging (MRI) studies have distinguished alcohol-related brain effects that are permanent from those that are reversible with abstinence. In support of postmortem neuropathological studies showing degeneration of white matter, MRI studies have shown a specific vulnerability of white matter to chronic alcohol exposure. Such studies have demonstrated white-matter volume deficits as well as damage to selective gray-matter structures. Diffusion tensor imaging (DTI), by permitting microstructural characterization of white matter, has extended MRI findings in alcoholics. MR spectroscopy (MRS) allows quantification of several metabolites that shed light on brain biochemical alterations caused by alcoholism. This article focuses on MRI, DTI, and MRS findings in neurological disorders that commonly co-occur with alcoholism, including Wernicke's encephalopathy, Korsakoff's syndrome, and hepatic encephalopathy. Also reviewed are neuroimaging findings in animal models of alcoholism and related neurological disorders. This report also suggests that the dynamic course of alcoholism presents a unique opportunity to examine brain structural and functional repair and recovery.
View details for PubMedID 28988573
View details for PubMedCentralID PMC5513685
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Deviant functional activation and connectivity of the right insula are associated with lack of awareness of episodic memory impairment in nonamnesic alcoholism
CORTEX
2017; 95: 15–28
Abstract
A disorder of metamemory, expressed as unawareness of mnemonic ability, is typically associated with the profound amnesia of Korsakoff's Syndrome (KS). A similar but less severe type of limited awareness can also occur in non-KS alcoholism and is observed as an impairment in generating Feeling-of-Knowing (FOK) predictions about future recognition performance. We previously found that FOK accuracy was selectively related to volumes of the insula in alcoholics involved in the present study. Unknown, however, are the neural substrates of unawareness of memory impairment in alcoholism. A task-activated fMRI paradigm served to identify neural nodes and networks implicated in inaccurate self-estimation of mnemonic ability in sober alcoholics while they made prospective FOK judgments in an episodic memory paradigm. Lower activation in the right insula correlated with greater overestimations of future memory abilities in alcoholics. Weaker connectivity of the right insula with the left dorsal anterior cingulate cortex, a node of the salience network, and stronger connectivity of the right insula with the right ventromedial prefrontal cortex (vmPFC), a node of the default mode network (DMN), co-occurred in alcoholics relative to the controls. Specifically, alcoholics, who failed to desynchronize insula-vmPFC activity, had greater overestimation of their memory predictions and poorer recognition performance. This study provides novel support that deviant functional activation and connectivity involving the right insula, a hub of the salience network, appears to participate in disrupting metamemory functioning in alcoholics. Compromised FOK performance might result from disturbance of the switching mechanism between brain networks serving self-referential processes (i.e., DMN network) and networks serving externally-driven activities like memory monitoring (i.e., fronto-parietal network). Thus, compromise in insular network coupling could be a neural mechanism underlying anosognosia for subtle mnemonic impairment in nonamnesic alcoholism.
View details for PubMedID 28806707
View details for PubMedCentralID PMC5626611
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Eveningness and Later Sleep Timing Are Associated with Greater Risk for Alcohol and Marijuana Use in Adolescence: Initial Findings from the National Consortium on Alcohol and Neurodevelopment in Adolescence Study.
Alcoholism, clinical and experimental research
2017; 41 (6): 1154-1165
Abstract
Abundant cross-sectional evidence links eveningness (a preference for later sleep-wake timing) and increased alcohol and drug use among adolescents and young adults. However, longitudinal studies are needed to examine whether eveningness is a risk factor for subsequent alcohol and drug use, particularly during adolescence, which is marked by parallel peaks in eveningness and risk for the onset of alcohol use disorders. This study examined whether eveningness and other sleep characteristics were associated with concurrent or subsequent substance involvement in a longitudinal study of adolescents.Participants were 729 adolescents (368 females; age 12 to 21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence study. Associations between the sleep variables (circadian preference, sleep quality, daytime sleepiness, sleep timing, and sleep duration) and 3 categorical substance variables (at-risk alcohol use, alcohol bingeing, and past-year marijuana use [y/n]) were examined using ordinal and logistic regression with baseline age, sex, race, ethnicity, socioeconomic status, and psychiatric problems as covariates.At baseline, greater eveningness was associated with greater at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed similar associations across the 3 substance outcomes at baseline. Greater baseline eveningness was also prospectively associated with greater bingeing and past-year use of marijuana at the 1-year follow-up, after covarying for baseline bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and shorter baseline weekday sleep duration, were similarly associated with greater bingeing and past-year use of marijuana at the 1-year follow-up after covarying for baseline values.Findings suggest that eveningness and sleep timing may be under recognized risk factors and future areas of intervention for adolescent involvement in alcohol and marijuana that should be considered along with other previously identified sleep factors such as insomnia and insufficient sleep.
View details for DOI 10.1111/acer.13401
View details for PubMedID 28421617
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Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains.
Cerebral cortex
2017: 1-15
View details for DOI 10.1093/cercor/bhx014
View details for PubMedID 28168274
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Effects of Childhood Trauma and Alcoholism History on Neuropsychological Performance in Adults with HIV Infection: An Initial Study.
Journal of HIV/AIDS and infectious diseases
2017; 4 (1)
Abstract
Childhood trauma carries heightened risk for neuropsychological impairment and is a frequent concomitant of HIV infection (H) and alcoholism (Alc). Little is known about compounded effects of childhood trauma and these diseases on cognitive and motor functioning. We queried the relation between childhood trauma history (experiencing at least 1 of 13 specified traumas before age 18) and cognitive and motor performance in HIV infection with and without lifetime alcoholism.Relations between childhood trauma history (Tr) and four performance domains (episodic memory, information processing speed, executive function, and fine motor function) were examined via ANCOVAs covarying for age and education in four HIV groups: 21 H+Alc+Tr, 19 H+Alc, 19 H+Tr, and 25 HComp (H comparison group without Tr or Alc).H+Tr, irrespective of Alc, performed poorly on the episodic memory domain. Specifically, immediate and delayed verbal recall, and immediate visual recall were affected in those with HIV and history of childhood trauma with or without alcoholism history. By contrast, H+Alc+Tr performed faster than H+Alc or H+Tr in information processing speed.The findings of poorer episodic memory in HIV infection with childhood trauma history corroborates previous reports and now extends findings to H+Alc+Tr trimorbidity. The novel interaction of alcoholism and trauma in HIV infection suggests that information processing speed is slowed with trauma history or alcoholism history alone in HIV but not with HIV+Alc+Tr trimorbidity, possibly reflecting greater impulsivity and hyperarousal in multiply-affected individuals.
View details for DOI 10.17303/jaid.2017.3.101
View details for PubMedID 38481564
View details for PubMedCentralID PMC10936226
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Effects of prior testing lasting a full year in NCANDA adolescents: Contributions from age, sex, socioeconomic status, ethnicity, site, family history of alcohol or drug abuse, and baseline performance.
Developmental cognitive neuroscience
2017; 24: 72-83
Abstract
Longitudinal study provides a robust method for tracking developmental trajectories. Yet inherent problems of retesting pose challenges in distinguishing biological developmental change from prior testing experience. We examined factors potentially influencing change scores on 16 neuropsychological test composites over 1year in 568 adolescents in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) project. The twice-minus-once-tested method revealed that performance gain was mainly attributable to testing experience (practice) with little contribution from predicted developmental effects. Group mean practice slopes for 13 composites indicated that 60% to ∼100% variance was attributable to test experience; General Ability accuracy showed the least practice effect (29%). Lower baseline performance, especially in younger participants, was a strong predictor of greater gain. Contributions from age, sex, ethnicity, examination site, socioeconomic status, or family history of alcohol/substance abuse were nil to small, even where statistically significant. Recognizing that a substantial proportion of change in longitudinal testing, even over 1-year, is attributable to testing experience indicates caution against assuming that performance gain observed during periods of maturation necessarily reflects development. Estimates of testing experience, a form of learning, may be a relevant metric for detecting interim influences, such as alcohol use or traumatic episodes, on behavior.
View details for DOI 10.1016/j.dcn.2017.01.003
View details for PubMedID 28214667
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Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders.
Neuropharmacology
2017
Abstract
Descriptions of the cognitive functions affected by alcohol use disorders (AUD) often highlight dysfunction of executive processes such attention, inhibitory control, working memory, and cognitive flexibility. Such complex cognitive functions have historically been ascribed to the prefrontal cortex. AUD, however, disrupts extensive areas of the brain. Structural and functional MRI studies suggest a central role for degradation of circuitry originating in the prefrontal cortex including nodes in widespread brain regions. This review features fronto-fugal circuits affected by AUD including frontocerebellar, frontolimbic, and frontostriatal networks and their relations to the salient, enduring, and debilitating cognitive and motor deficits reported in AUD.
View details for DOI 10.1016/j.neuropharm.2017.01.018
View details for PubMedID 28118989
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The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.
Brain imaging and behavior
2016: -?
Abstract
Emotional dysregulation in alcoholism (ALC) may result from disturbed inhibitory mechanisms. We therefore tested emotion and alcohol cue reactivity and inhibitory processes using negative priming. To test the neural correlates of cue reactivity and negative priming, 26 ALC and 26 age-matched controls underwent functional MRI performing a Stroop color match-to-sample task. In cue reactivity trials, task-irrelevant emotion and alcohol-related pictures were interspersed between color samples and color words. In negative priming trials, pictures primed the semantic content of an alcohol or emotion Stroop word. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to primed trials. For cue reactivity to emotion and alcohol pictures, ALC showed midbrain-limbic activation. By contrast, controls activated frontoparietal executive control regions. Greater midbrain-hippocampal activation in ALC correlated with higher amounts of lifetime alcohol consumption and higher anxiety. With negative priming, ALC exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal activation to alcohol-priming correlated with less craving and to emotion-priming with fewer depressive symptoms. The findings suggest that neurofunctional systems in ALC can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.
View details for PubMedID 27815773
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Transient CNS responses to repeated binge ethanol treatment.
Addiction biology
2016; 21 (6): 1199-1216
Abstract
The effects of ethanol (EtOH) on in vivo magnetic resonance (MR)-detectable brain measures across repeated exposures have not previously been reported. Of 28 rats weighing 340.66 ± 21.93 g at baseline, 15 were assigned to an EtOH group and 13 to a control group. Animals were exposed to five cycles of 4 days of intragastric (EtOH or dextrose) treatment and 10 days of recovery. Rats in both groups had structural MR imaging and whole-brain MR spectroscopy (MRS) scans at baseline, immediately following each binge period and after each recovery period (total = 11 scans per rat). Blood alcohol level at each of the five binge periods was ~300 mg/dl. Blood drawn at the end of the experiment did not show group differences for thiamine or its phosphate derivatives. Postmortem liver histopathology provided no evidence for hepatic steatosis, alcoholic hepatitis or alcoholic cirrhosis. Cerebrospinal fluid volumes of the lateral ventricles and cisterns showed enlargement with each binge EtOH exposure but recovery with each abstinence period. Similarly, changes in MRS metabolite levels were transient: levels of N-acetylaspartate and total creatine decreased, while those of choline-containing compounds and the combined resonance from glutamate and glutamine increased with each binge EtOH exposure cycle and then recovered during each abstinence period. Changes in response to EtOH were in expected directions based on previous single-binge EtOH exposure experiments, but the current MR findings do not provide support for accruing changes with repeated binge EtOH exposure.
View details for DOI 10.1111/adb.12290
View details for PubMedID 26283309
View details for PubMedCentralID PMC4801670
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Impairments in Component Processes of Executive Function and Episodic Memory in Alcoholism, HIV Infection, and HIV Infection with Alcoholism Comorbidity.
Alcoholism, clinical and experimental research
2016
Abstract
Executive functioning and episodic memory impairment occur in HIV infection (HIV) and chronic alcoholism (ALC). Comorbidity of these conditions (HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy.HIV, ALC, HIV + ALC, and normal controls (NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times.HIV, ALC, and HIV + ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV + ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV + ALC, age was a unique predictor of Episodic Memory Composite score.Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV + ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging.
View details for DOI 10.1111/acer.13250
View details for PubMedID 27759882
View details for PubMedCentralID PMC5133188
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Structural brain anomalies in healthy adolescents in the NCANDA cohort: relation to neuropsychological test performance, sex, and ethnicity.
Brain imaging and behavior
2016: -?
Abstract
Structural MRI of volunteers deemed "normal" following clinical interview provides a window into normal brain developmental morphology but also reveals unexpected dysmorphology, commonly known as "incidental findings." Although unanticipated, these anatomical findings raise questions regarding possible treatment that could even ultimately require neurosurgical intervention, which itself carries significant risk but may not be indicated if the anomaly is nonprogressive or of no functional consequence. Neuroradiological readings of 833 structural MRI from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) cohort found an 11.8 % incidence of brain structural anomalies, represented proportionately across the five collection sites and ethnic groups. Anomalies included 26 mega cisterna magna, 15 subarachnoid cysts, 12 pineal cysts, 12 white matter dysmorphologies, 5 tonsillar ectopias, 5 prominent perivascular spaces, 5 gray matter heterotopias, 4 pituitary masses, 4 excessively large or asymmetrical ventricles, 4 cavum septum pellucidum, 3 developmental venous anomalies, 1 exceptionally large midsagittal vein, and single cases requiring clinical followup: cranio-cervical junction stenosis, parietal cortical mass, and Chiari I malformation. A case of possible demyelinating disorder (e.g., neuromyelitis optica or multiple sclerosis) newly emerged at the 1-year NCANDA followup, requiring clinical referral. Comparing test performance of the 98 anomalous cases with 619 anomaly-free no-to-low alcohol consuming adolescents revealed significantly lower scores on speed measures of attention and motor functions; these differences were not attributed to any one anomaly subgroup. Further, we devised an automated approach for quantifying posterior fossa CSF volumes for detection of mega cisterna magna, which represented 26.5 % of clinically identified anomalies. Automated quantification fit a Gaussian distribution with a rightward skew. Using a 3SD cut-off, quantification identified 22 of the 26 clinically-identified cases, indicating that cases with percent of CSF in the posterior-inferior-middle aspect of the posterior fossa ≥3SD merit further review, and support complementing clinical readings with objective quantitative analysis. Discovery of asymptomatic brain structural anomalies, even when no clinical action is indicated, can be disconcerting to the individual and responsible family members, raising a disclosure dilemma: refrain from relating the incidental findings to avoid unnecessary alarm or anxiety; or alternatively, relate the neuroradiological findings as "normal variants" to the study volunteers and family, thereby equipping them with knowledge for the future should they have the occasion for a brain scan following an illness or accident that the incidental findings predated the later event.
View details for PubMedID 27722828
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Adolescent Development of Cortical and White Matter Structure in the NCANDA Sample: Role of Sex, Ethnicity, Puberty, and Alcohol Drinking.
Cerebral cortex
2016; 26 (10): 4101-4121
Abstract
Brain structural development continues throughout adolescence, when experimentation with alcohol is often initiated. To parse contributions from biological and environmental factors on neurodevelopment, this study used baseline National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) magnetic resonance imaging (MRI) data, acquired in 674 adolescents meeting no/low alcohol or drug use criteria and 134 adolescents exceeding criteria. Spatial integrity of images across the 5 recruitment sites was assured by morphological scaling using Alzheimer's disease neuroimaging initiative phantom-derived volume scalar metrics. Clinical MRI readings identified structural anomalies in 11.4%. Cortical volume and thickness were smaller and white matter volumes were larger in older than in younger adolescents. Effects of sex (male > female) and ethnicity (majority > minority) were significant for volume and surface but minimal for cortical thickness. Adjusting volume and area for supratentorial volume attenuated or removed sex and ethnicity effects. That cortical thickness showed age-related decline and was unrelated to supratentorial volume is consistent with the radial unit hypothesis, suggesting a universal neural development characteristic robust to sex and ethnicity. Comparison of NCANDA with PING data revealed similar but flatter, age-related declines in cortical volumes and thickness. Smaller, thinner frontal, and temporal cortices in the exceeds-criteria than no/low-drinking group suggested untoward effects of excessive alcohol consumption on brain structural development.
View details for DOI 10.1093/cercor/bhv205
View details for PubMedID 26408800
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"Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction": Correction to Sullivan et al. (2016).
Neuropsychology
2016; 30 (7): 829
Abstract
Reports an error in "Cognitive, emotion control, and motor performance of adolescents in the NCANDA study: Contributions from alcohol consumption, age, sex, ethnicity, and family history of addiction" by Edith V. Sullivan, Ty Brumback, Susan F. Tapert, Rosemary Fama, Devin Prouty, Sandra A. Brown, Kevin Cummins, Wesley K. Thompson, Ian M. Colrain, Fiona C. Baker, Michael D. De Bellis, Stephen R. Hooper, Duncan B. Clark, Tammy Chung, Bonnie J. Nagel, B. Nolan Nichols, Torsten Rohlfing, Weiwei Chu, Kilian M. Pohl and Adolf Pfefferbaum (Neuropsychology, 2016[May], Vol 30[4], 449-473). A problem with a computation to invert speed scores is noted and explained in this correction. All statements indicating group differences in speed scores, as well as Table 5 and Figure 8A, have been corrected in the online version of this article. (The following abstract of the original article appeared in record 2016-00613-001.)To investigate development of cognitive and motor functions in healthy adolescents and to explore whether hazardous drinking affects the normal developmental course of those functions.Participants were 831 adolescents recruited across 5 United States sites of the National Consortium on Alcohol and NeuroDevelopment in Adolescence 692 met criteria for no/low alcohol exposure, and 139 exceeded drinking thresholds. Cross-sectional, baseline data were collected with computerized and traditional neuropsychological tests assessing 8 functional domains expressed as composite scores. General additive modeling evaluated factors potentially modulating performance (age, sex, ethnicity, socioeconomic status, and pubertal developmental stage).Older no/low-drinking participants achieved better scores than younger ones on 5 accuracy composites (general ability, abstraction, attention, emotion, and balance). Speeded responses for attention, motor speed, and general ability were sensitive to age and pubertal development. The exceeds-threshold group (accounting for age, sex, and other demographic factors) performed significantly below the no/low-drinking group on balance accuracy and on general ability, attention, episodic memory, emotion, and motor speed scores and showed evidence for faster speed at the expense of accuracy. Delay Discounting performance was consistent with poor impulse control in the younger no/low drinkers and in exceeds-threshold drinkers regardless of age.Higher achievement with older age and pubertal stage in general ability, abstraction, attention, emotion, and balance suggests continued functional development through adolescence, possibly supported by concurrently maturing frontal, limbic, and cerebellar brain systems. Determination of whether low scores by the exceeds-threshold group resulted from drinking or from other preexisting factors requires longitudinal study.
View details for DOI 10.1037/neu0000306
View details for PubMedID 27504610
View details for PubMedCentralID PMC7405886
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Extracting patterns of morphometry distinguishing HIV associated neurodegeneration from mild cognitive impairment via group cardinality constrained classification.
Human brain mapping
2016
Abstract
HIV-Associated Neurocognitive Disorder (HAND) is the most common constellation of cognitive dysfunctions in chronic HIV infected patients age 60 or older in the U.S. Only few published methods assist in distinguishing HAND from other forms of age-associated cognitive decline, such as Mild Cognitive Impairment (MCI). In this report, a data-driven, nonparameteric model to identify morphometric patterns separating HAND from MCI due to non-HIV conditions in this older age group was proposed. This model enhanced the potential for group separation by combining a smaller, longitudinal data set containing HAND samples with a larger, public data set including MCI cases. Using cross-validation, a linear model on healthy controls to harmonize the volumetric scores extracted from MRIs for demographic and acquisition differences between the two independent, disease-specific data sets was trained. Next, patterns distinguishing HAND from MCI via a group sparsity constrained logistic classifier were identified. Unlike existing approaches, our classifier directly solved the underlying minimization problem by decoupling the minimization of the logistic regression function from enforcing the group sparsity constraint. The extracted patterns consisted of eight regions that distinguished HAND from MCI on a significant level while being indifferent to differences in demographics and acquisition between the two sets. Individually selecting regions through conventional morphometric group analysis resulted in a larger number of regions that were less accurate. In conclusion, simultaneously analyzing all brain regions and time points for disease specific patterns contributed to distinguishing with high accuracy HAND-related impairment from cognitive impairment found in the HIV uninfected, MCI cohort. Hum Brain Mapp 37:4523-4538, 2016. © 2016 Wiley Periodicals, Inc.
View details for DOI 10.1002/hbm.23326
View details for PubMedID 27489003
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Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates
CORTEX
2016; 81: 192-202
View details for DOI 10.1016/j.cortex.2016.05.002
View details for Web of Science ID 000381163900017
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Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates.
Cortex; a journal devoted to the study of the nervous system and behavior
2016; 81: 192-202
Abstract
Metamemory refers to personal knowledge about one's own memory ability that invokes cognitive processes relevant to monitoring and controlling memory. An impaired monitoring system can potentially result in unawareness of symptoms as can occur in addiction denial. Monitoring processes can be assessed with prospective measures such as Feeling-Of-Knowing (FOK) judgments on prediction of future recognition performance, or retrospective confidence judgments (RCJ) made on previous memory performance. Alcoholic patients with amnesia showed poor FOK but intact RCJ. The neuropsychological continuum from mild to moderate deficits in nonamnesic to amnesic alcoholism raised the possibility that alcoholics uncomplicated by clinically-detectable amnesia may suffer anosognosia for their mild memory deficits. Herein 24 abstinent alcoholics and 26 age-matched controls completed an episodic memory paradigm including prospective FOK and retrospective RCJ monitoring measures and underwent 3T structural magnetic resonance imaging. Alcoholics were less accurate than controls in recognition and in assessing their future recognition performance, which was marked by overestimation, but were as accurate as controls on confidence ratings of actual recognition performance. Examination of brain structure-function relations revealed a double dissociation where FOK accuracy was selectively related to insular volume, and retrospective confidence accuracy was selectively related to frontolimbic structural volumes. Impaired FOK with intact RCJ was consistent with mild anosognosia and suggested evidence for neuropsychological and neural mechanisms of unawareness in addiction.
View details for DOI 10.1016/j.cortex.2016.05.002
View details for PubMedID 27244277
View details for PubMedCentralID PMC4958575
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Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo
PSYCHOPHARMACOLOGY
2016; 233 (14): 2675-2686
Abstract
Serious neurological concomitants of alcoholism include Wernicke's encephalopathy (WE), Korsakoff's syndrome (KS), and hepatic encephalopathy (HE).This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation.Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment.Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls.These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.
View details for DOI 10.1007/s00213-016-4313-y
View details for Web of Science ID 000378874600004
View details for PubMedID 27129864
View details for PubMedCentralID PMC4919142
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Cognitive, Emotion Control, and Motor Performance of Adolescents in the NCANDA Study: Contributions From Alcohol Consumption, Age, Sex, Ethnicity, and Family History of Addiction
NEUROPSYCHOLOGY
2016; 30 (4): 449-473
Abstract
To investigate development of cognitive and motor functions in healthy adolescents and to explore whether hazardous drinking affects the normal developmental course of those functions.Participants were 831 adolescents recruited across 5 United States sites of the National Consortium on Alcohol and NeuroDevelopment in Adolescence 692 met criteria for no/low alcohol exposure, and 139 exceeded drinking thresholds. Cross-sectional, baseline data were collected with computerized and traditional neuropsychological tests assessing 8 functional domains expressed as composite scores. General additive modeling evaluated factors potentially modulating performance (age, sex, ethnicity, socioeconomic status, and pubertal developmental stage).Older no/low-drinking participants achieved better scores than younger ones on 5 accuracy composites (general ability, abstraction, attention, emotion, and balance). Speeded responses for attention, motor speed, and general ability were sensitive to age and pubertal development. The exceeds-threshold group (accounting for age, sex, and other demographic factors) performed significantly below the no/low-drinking group on balance accuracy and on general ability, attention, episodic memory, emotion, and motor speed scores and showed evidence for faster speed at the expense of accuracy. Delay Discounting performance was consistent with poor impulse control in the younger no/low drinkers and in exceeds-threshold drinkers regardless of age.Higher achievement with older age and pubertal stage in general ability, abstraction, attention, emotion, and balance suggests continued functional development through adolescence, possibly supported by concurrently maturing frontal, limbic, and cerebellar brain systems. Determination of whether low scores by the exceeds-threshold group resulted from drinking or from other preexisting factors requires longitudinal study. (PsycINFO Database Record
View details for DOI 10.1037/neu0000259
View details for PubMedID 26752122
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Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse
PSYCHIATRY RESEARCH-NEUROIMAGING
2016; 250: 42-49
Abstract
Magnetic resonance spectroscopy (MRS) studies in alcohol use disorder (AUD) typically report lower levels of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in several brain regions. Metabolite levels, however, are labile and can be affected by several competing factors, some related to drinking variables.. This in vivo MRS study included 20 recently sober (19.6±12.6 days) individuals with AUD and 15 controls. MRS was performed in single voxels placed in frontal white matter and thalamic regions using Constant-Time Point Resolved Spectroscopy (CT-PRESS) for absolute quantification of NAA, Cho, total creatine (tCr), and glutamate (Glu). A trend toward a thalamic NAA deficit in the total AUD group compared with controls was attributable to the subgroup of alcoholics who relapsed 3 or so months after scanning. In the total AUD group, frontal and thalamic NAA and Cho levels were lower with more recent drinking; frontal and thalamic Cho levels were also lower in AUD individuals with past stimulant abuse. Thalamic Cho levels were higher in binge-drinking AUD individuals and in those with longer length of alcohol dependence. MRS-visible metabolite peaks appear to be modulated by variables related to drinking behaviors, suggesting a sensitivity of MRS in tracking and predicting the dynamic course of alcoholism.
View details for DOI 10.1016/j.pscychresns.2016.01.015
View details for Web of Science ID 000375160200007
View details for PubMedID 27035062
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Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study
NEUROIMAGE
2016; 130: 194-213
Abstract
Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.
View details for DOI 10.1016/j.neuroimage.2016.01.061
View details for Web of Science ID 000372745600018
View details for PubMedCentralID PMC4808415
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Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study.
NeuroImage
2016; 130: 194-213
Abstract
Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.
View details for DOI 10.1016/j.neuroimage.2016.01.061
View details for PubMedID 26872408
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Brain responses to emotional salience and reward in alcohol use disorder.
Brain imaging and behavior
2016; 10 (1): 136-146
Abstract
Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executive control ability and relapse propensity during abstinence.
View details for DOI 10.1007/s11682-015-9374-8
View details for PubMedID 25875013
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Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-C-13]pyruvate
NMR IN BIOMEDICINE
2015; 28 (12): 1671-1677
Abstract
To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13) C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13) C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4 -treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4 -treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4 -treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4 -treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13) C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
View details for DOI 10.1002/nbm.3431
View details for Web of Science ID 000367315100007
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The Resting Brain of Alcoholics
CEREBRAL CORTEX
2015; 25 (11): 4155-4168
Abstract
Chronic alcohol consumption affects multiple cognitive processes supported by far-reaching cerebral networks. To identify neurofunctional mechanisms underlying selective deficits, 27 sober alcoholics and 26 age-matched controls underwent resting-state functional magnetic resonance imaging and neuropsychological testing. Functional connectivity analysis assessed the default mode network (DMN); integrative executive control (EC), salience (SA), and attention (AT) networks; primary somatosensory, auditory, and visual (VI) input networks; and subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive overlap of intrinsic connectivity in all brain networks examined, suggesting overall integrity of large-scale functional networks. Despite these similar patterns, connectivity analyses identified network-specific differences of weaker within-network connectivity and expanded connectivity to regions outside the main networks in alcoholics compared with controls. For AT and VI networks, better task performance was related to expanded connectivity in alcoholism, supporting the concept of network expansion as a neural mechanism for functional compensation. For default mode, SA, RW, and EC networks, both weaker within-network and expanded outside-network connectivity correlated with poorer performance and mood. Current smoking contributed to some of these abnormalities in connectivity. The observed pattern of resting-state connectivity might reflect neural vulnerability of intrinsic networking in alcoholics and suggests a mechanism to explain signature impairments in EM, RW evaluation, and EC ability.
View details for DOI 10.1093/cercor/bhu134
View details for Web of Science ID 000366463300012
View details for PubMedID 24935777
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The National Consortium on Alcohol and Neuro-Development in Adolescence (NCANDA): A Multisite Study of Adolescent Development and Substance Use
JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
2015; 76 (6): 895-908
Abstract
During adolescence, neurobiological maturation occurs concurrently with social and interpersonal changes, including the initiation of alcohol and other substance use. The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) is designed to disentangle the complex relationships between onset, escalation, and desistance of alcohol use and changes in neurocognitive functioning and neuromaturation.A sample of 831 youth, ages 12-21 years, was recruited at five sites across the United States, oversampling those at risk for alcohol use problems. Most (83%) had limited or no history of alcohol or other drug use, and a smaller portion (17%) exceeded drinking thresholds. A comprehensive assessment of biological development, family background, psychiatric symptomatology, and neuropsychological functioning-in addition to anatomical, diffusion, and functional brain magnetic resonance imaging-was completed at baseline.The NCANDA sample of youth is nationally representative of sex and racial/ethnic groups. More than 50% have at least one risk characteristic for subsequent heavy drinking (e.g., family history, internalizing or externalizing symptoms). As expected, those who exceeded drinking thresholds (n = 139) differ from those who did not (n = 692) on identified factors associated with early alcohol use and problems.NCANDA successfully recruited a large sample of adolescents and comprehensively assessed psychosocial functioning across multiple domains. Based on the sample's risk profile, NCANDA is well positioned to capture the transition into drinking and alcohol problems in a large portion of the cohort, as well as to help disentangle the associations between alcohol use, neurobiological maturation, and neurocognitive development and functioning.
View details for PubMedID 26562597
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Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized [1-(13) C]pyruvate.
NMR in biomedicine
2015
Abstract
To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized (13) C-pyruvate to assess metabolic parameters in a CCl4 model of liver damage in rats. Dynamic 3D (13) C chemical shift imaging data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4 -treated rats. At 12 time points at 5 s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine, and lactate. These measurements were compared with standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4 -treated but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with these results, metabolic imaging revealed an increased alanine/pyruvate ratio in liver of CCl4 -treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4 -treated compared with control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using (13) C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo. Copyright © 2015 John Wiley & Sons, Ltd.
View details for DOI 10.1002/nbm.3431
View details for PubMedID 26474216
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Cross-sectional versus longitudinal estimates of age-related changes in the adult brain: overlaps and discrepancies
NEUROBIOLOGY OF AGING
2015; 36 (9): 2563-2567
View details for DOI 10.1016/j.neurobiolaging.2015.05.005
View details for Web of Science ID 000358803400012
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Cross-sectional versus longitudinal estimates of age-related changes in the adult brain: overlaps and discrepancies.
Neurobiology of aging
2015; 36 (9): 2563-2567
Abstract
The healthy adult brain undergoes tissue volume decline with age, but contradictory findings abound regarding rate of change. To identify a source of this discrepancy, we present contrasting statistical approaches to estimate hippocampal volume change with age based on 200 longitudinally-acquired magnetic resonance imaging in 70 healthy adults, age 20-70 years, who had 2-5 magnetic resonance imaging collected over 6 months to 8 years. Linear mixed-effects modeling using volume trajectories over age for each subject revealed significantly negative slopes with aging after a linear decline with a suggestion of acceleration in older individuals. By contrast, general linear modeling using either the first observation only of each subject or all observations treated independently (thereby disregarding trajectories) indicated no significant correlation between volume and age. Entering a quadratic term into the linear model yielded a biologically plausible function that was not supported by longitudinal analysis. The results underscore the importance of analyses that incorporate the trajectory of individuals in the study of brain aging.
View details for DOI 10.1016/j.neurobiolaging.2015.05.005
View details for PubMedID 26059713
View details for PubMedCentralID PMC4523414
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Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease
BRAIN IMAGING AND BEHAVIOR
2015; 9 (3): 619-638
Abstract
Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.
View details for DOI 10.1007/s11682-014-9317-9
View details for Web of Science ID 000361604300021
View details for PubMedCentralID PMC4385510
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Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.
Brain imaging and behavior
2015; 9 (3): 619-638
Abstract
Parkinson's disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG-cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen-medial parietal and pallidum-occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate-supramarginal gyrus and pallidum-inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal-cortical connectivity, specifically between caudate-prefrontal, caudate-precuneus, and putamen-motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance.
View details for DOI 10.1007/s11682-014-9317-9
View details for PubMedID 25280970
View details for PubMedCentralID PMC4385510
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Brain pathways to recovery from alcohol dependence
ALCOHOL
2015; 49 (5): 435-452
Abstract
This article highlights the research presentations at the satellite symposium on "Brain Pathways to Recovery from Alcohol Dependence" held at the 2013 Society for Neuroscience Annual Meeting. The purpose of this symposium was to provide an up to date overview of research efforts focusing on understanding brain mechanisms that contribute to recovery from alcohol dependence. A panel of scientists from the alcohol and addiction research field presented their insights and perspectives on brain mechanisms that may underlie both recovery and lack of recovery from alcohol dependence. The four sessions of the symposium encompassed multilevel studies exploring mechanisms underlying relapse and craving associated with sustained alcohol abstinence, cognitive function deficit and recovery, and translational studies on preventing relapse and promoting recovery. Gaps in our knowledge and research opportunities were also discussed.
View details for DOI 10.1016/j.alcohol.2015.04.006
View details for PubMedID 26074423
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Brain Development in Heavy-Drinking Adolescents
AMERICAN JOURNAL OF PSYCHIATRY
2015; 172 (6): 531-542
Abstract
Heavy alcohol use during adolescence may alter the trajectory of normal brain development. The authors measured within-subject changes in regional brain morphometry over longer intervals and in larger samples of adolescents than previously reported and assessed differences between adolescents who remained nondrinkers and those who drank heavily during adolescence as well as differences between the sexes.The authors examined gray and white matter volume trajectories in 134 adolescents, of whom 75 transitioned to heavy drinking and 59 remained light drinkers or nondrinkers over roughly 3.5 years. Each underwent MRI scanning two to six times between ages 12 and 24 and was followed for up to 8 years. The volumes of the neocortex, allocortex, and white matter structures were measured using atlas-based parcellation with longitudinal registration. Linear mixed-effects models described differences in trajectories of heavy drinkers and nondrinkers over age; secondary analyses considered the contribution of other drug use to identified alcohol use effects.Heavy-drinking adolescents showed accelerated gray matter reduction in cortical lateral frontal and temporal volumes and attenuated white matter growth of the corpus callosum and pons relative to nondrinkers. These results were largely unchanged when use of marijuana and other drugs was examined. Male and female drinkers showed similar patterns of development trajectory abnormalities.Longitudinal analysis enabled detection of accelerated typical volume decline in frontal and temporal cortical volumes and attenuated growth in principal white matter structures in adolescents who started to drink heavily. These results provide a call for caution regarding heavy alcohol use during adolescence, whether heavy drinking is the sole cause or one of several in these alterations in brain development.
View details for DOI 10.1176/appi.ajp.2015.14101249
View details for Web of Science ID 000355642800009
View details for PubMedID 25982660
View details for PubMedCentralID PMC4451385
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Dynamic Responses of Selective Brain White Matter Fiber Tracts to Binge Alcohol and Recovery in the Rat
PLOS ONE
2015; 10 (4)
View details for DOI 10.1371/journal.pone.0124885
View details for Web of Science ID 000353211700127
View details for PubMedID 25894968
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Cognitive demands during quiet standing elicit truncal tremor in two frequency bands: differential relations to tissue integrity of corticospinal tracts and cortical targets
FRONTIERS IN HUMAN NEUROSCIENCE
2015; 9
View details for DOI 10.3389/fnhum.2015.00175
View details for Web of Science ID 000352655400001
View details for PubMedID 25904858
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Dynamic responses of selective brain white matter fiber tracts to binge alcohol and recovery in the rat.
PloS one
2015; 10 (4)
Abstract
To determine the dynamics of white matter vulnerability to excessive alcohol consumption, diffusion tensor imaging (DTI) was used in an animal model of alcohol exposure. Quantitative, in vivo fiber tracking results are presented from rats with DTI conducted at 3 time points: baseline; after 4 days of intragastric alcohol to blood alcohol levels of ~250 mg/dL; and after one week of recovery. Binge alcohol followed by a week of sobriety resulted in rapidly reversible decreases in fractional anisotropy (FA), a measure of the coherence of fiber tracts, in callosal genu and fimbria-fornix but not splenium; and increases in mean diffusivity (MD), an index of freely diffusing water in tissue, selective to the fimbria-fornix. These effects were confirmed with tract-based spatial statistics (TBSS). The directionality of changes in DTI metrics reproduce those observed in human alcoholism. That a single exposure to binge alcohol can cause substantial transient changes detectable in DTI metrics demonstrates the potential for rapid neuroplasticity.
View details for DOI 10.1371/journal.pone.0124885
View details for PubMedID 25894968
View details for PubMedCentralID PMC4403879
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Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States.
Frontiers in human neuroscience
2015; 9: 354-?
Abstract
Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS.
View details for DOI 10.3389/fnhum.2015.00354
View details for PubMedID 26157376
View details for PubMedCentralID PMC4477159
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Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation With Brain Iron in Normal Aging
IEEE TRANSACTIONS ON MEDICAL IMAGING
2015; 34 (1): 339-353
Abstract
There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or "QSIP." The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.
View details for DOI 10.1109/TMI.2014.2358552
View details for Web of Science ID 000346975900031
View details for PubMedID 25248179
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Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States.
Frontiers in human neuroscience
2015; 9: 354-?
View details for DOI 10.3389/fnhum.2015.00354
View details for PubMedID 26157376
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Cognitive demands during quiet standing elicit truncal tremor in two frequency bands: differential relations to tissue integrity of corticospinal tracts and cortical targets.
Frontiers in human neuroscience
2015; 9: 175-?
Abstract
The ability to stand quietly is disturbed by degradation of cerebellar systems. Given the complexity of sensorimotor integration invoked to maintain upright posture, the integrity of supratentorial brain structures may also contribute to quiet standing and consequently be vulnerable to interference from cognitive challenges. As cerebellar system disruption is a common concomitant of alcoholism, we examined 46 alcoholics and 43 controls with a force platform to derive physiological indices of quiet standing during cognitive (solving simple, mental arithmetic problems) and visual (eyes closed) challenges. Also tested were relations between tremor velocity and regional gray matter and white matter tissue quality measured with the diffusion tensor imaging (DTI) metric of mean diffusivity (MD), indexing disorganized microstructure. Spectral analysis of sway revealed greater tremor in alcoholic men than alcoholic women or controls. Cognitive dual-tasking elicited excessive tremor in two frequency bands, each related to DTI signs of degradation in separate brain systems: tremor velocity at a low frequency (2-5 Hz/0-2 Hz) correlated with higher MD in the cerebellar hemispheres and superior cingulate bundles, whereas tremor velocity at a higher frequency (5-7 Hz) correlated with higher MD in the motor cortex and internal capsule. These brain sites may represent "tremorgenic networks" that, when disturbed by disease and exacerbated by cognitive dual-tasking, contribute to postural instability, putting affected individuals at heightened risk for falling.
View details for DOI 10.3389/fnhum.2015.00175
View details for PubMedID 25904858
View details for PubMedCentralID PMC4387934
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Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics
PSYCHOPHARMACOLOGY
2014; 231 (23): 4443-4453
View details for DOI 10.1007/s00213-014-3594-2
View details for Web of Science ID 000344869900003
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Thalamic volume deficit contributes to procedural and explicit memory impairment in HIV infection with primary alcoholism comorbidity.
Brain imaging and behavior
2014; 8 (4): 611-620
Abstract
Component cognitive and motor processes contributing to diminished visuomotor procedural learning in HIV infection with comorbid chronic alcoholism (HIV+ALC) include problems with attention and explicit memory processes. The neural correlates associated with this constellation of cognitive and motor processes in HIV infection and alcoholism have yet to be delineated. Frontostriatal regions are affected in HIV infection, frontothalamocerebellar regions are affected in chronic alcoholism, and frontolimbic regions are likely affected in both; all three of these systems have the potential of contributing to both visuomotor procedural learning and explicit memory processes. Here, we examined the neural correlates of implicit memory, explicit memory, attention, and motor tests in 26 HIV+ALC (5 with comorbidity for nonalcohol drug abuse/dependence) and 19 age-range matched healthy control men. Parcellated brain volumes, including cortical, subcortical, and allocortical regions, as well as cortical sulci and ventricles, were derived using the SRI24 brain atlas. Results indicated that smaller thalamic volumes were associated with poorer performance on tests of explicit (immediate and delayed) and implicit (visuomotor procedural) memory in HIV+ALC. By contrast, smaller hippocampal volumes were associated with lower scores on explicit, but not implicit memory. Multiple regression analyses revealed that volumes of both the thalamus and the hippocampus were each unique independent predictors of explicit memory scores. This study provides evidence of a dissociation between implicit and explicit memory tasks in HIV+ALC, with selective relationships observed between hippocampal volume and explicit but not implicit memory, and highlights the relevance of the thalamus to mnemonic processes.
View details for DOI 10.1007/s11682-013-9286-4
View details for PubMedID 24421067
View details for PubMedCentralID PMC4097992
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Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy
EXPERIMENTAL NEUROLOGY
2014; 261: 109-119
View details for DOI 10.1016/j.expneurol.2014.06.015
View details for Web of Science ID 000343531500011
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Imaging neuroinflammation? A perspective from MR spectroscopy.
Brain pathology
2014; 24 (6): 654-664
Abstract
Neuroinflammatory mechanisms contribute to the brain pathology resulting from human immunodeficiency virus (HIV) infection. Magnetic resonance spectroscopy (MRS) has been touted as a suitable method for discriminating in vivo markers of neuroinflammation. The present MRS study was conducted in four groups: alcohol dependent (A, n = 37), HIV-infected (H, n = 33), alcohol dependent + HIV infected (HA, n = 38) and healthy control (C, n = 62) individuals to determine whether metabolites would change in a pattern reflecting neuroinflammation. Significant four-group comparisons were evident only for striatal choline-containing compounds (Cho) and myo-inositol (mI), which follow-up analysis demonstrated were due to higher levels in HA compared with C individuals. To explore the potential relevance of elevated Cho and mI, correlations between blood markers, medication status and alcohol consumption were evaluated in H + HA subjects. Having an acquired immune deficiency syndrome (AIDS)-defining event or hepatitis C was associated with higher Cho; lower Cho levels, however, were associated with low thiamine levels and with highly active antiretroviral HIV treatment (HAART). Higher levels of mI were related to greater lifetime alcohol consumed, whereas HAART was associated with lower mI levels. The current results suggest that competing mechanisms can influence in vivo Cho and mI levels, and that elevations in these metabolites cannot necessarily be interpreted as reflecting a single underlying mechanism, including neuroinflammation.
View details for DOI 10.1111/bpa.12197
View details for PubMedID 25345895
View details for PubMedCentralID PMC4493672
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Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy.
Experimental neurology
2014; 261: 109-119
Abstract
Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke's encephalopathy (WE). Recent work building upon early observations in animal models of thiamine deficiency has demonstrated an inflammatory component to the neuropathology observed in thiamine deficiency. The present, multilevel study including in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) and postmortem quantification of chemokine and cytokine proteins sought to determine whether a combination of these in vivo neuroimaging tools could be used to characterize an in vivo MR signature for neuroinflammation. Thiamine deficiency for 12days was used to model neuroinflammation; glucose loading in thiamine deficiency was used to accelerate neurodegeneration. Among 38 animals with regional brain tissue assayed postmortem for cytokine/chemokine protein levels, three groups of rats (controls+glucose, n=6; pyrithiamine+saline, n=5; pyrithiamine+glucose, n=13) underwent MRI/MRS at baseline (time 1), after 12days of treatment (time 2), and 3h after challenge (glucose or saline, time 3). In the thalamus of glucose-challenged, thiamine deficient animals, correlations between in vivo measures of pathology (lower levels of N-acetyle aspartate and higher levels of lactate) and postmortem levels of monocyte chemotactic protein-1 (MCP-1, also known as chemokine ligand 2, CCL2) support a role for this chemokine in thiamine deficiency-related neurodegeneration, but do not provide a unique in vivo signature for neuroinflammation.
View details for DOI 10.1016/j.expneurol.2014.06.015
View details for PubMedID 24973622
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Imaging Neuroinflammation? A Perspective from MR Spectroscopy
BRAIN PATHOLOGY
2014; 24 (6): 654-664
View details for DOI 10.1111/bpa.12197
View details for Web of Science ID 000344347000011
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Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: Comparison of effects in France and the United States.
Human brain mapping
2014; 35 (9): 4635-4653
Abstract
Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1-weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences. Hum Brain Mapp 35:4635-4653, 2014. © 2014 Wiley Periodicals, Inc.
View details for DOI 10.1002/hbm.22500
View details for PubMedID 24639416
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White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study.
The lancet. Psychiatry
2014; 1 (3): 202-212
Abstract
Alcohol dependence exacts a toll on brain white matter microstructure, which has the potential of repair with prolonged sobriety. Diffusion tensor imaging (DTI) enables in-vivo quantification of tissue constituents and localisation of tracts potentially affected in alcohol dependence and its recovery. We did an extended longitudinal study of alcoholism's trajectory of effect on selective fibre bundles with sustained sobriety or decline with relapse.Participants were drawn from a longitudinal, 1·5T DTI database of 841 scans of individuals with various medical or neuropsychiatric conditions and normal ageing. Participants diagnosed with alcohol dependence had to meet the criteria from DSM-IV for alcohol dependence. Controls were screened and free of any DSM-IV axis I diagnosis, including being without history of alcohol or drug abuse or dependence. Tract-based spatial statistics (TBSS) quantified white matter integrity throughout the brain in 47 alcohol-dependent individuals and 56 controls examined 2-5 times over 1-8 year intervals. We identified regions showing group differences with a white matter atlas. For macrostructural comparison, we measured corpus callosum and centrum semiovale volumes on MRI.This study took place in the USA, between June 23, 2000, and Sept 6, 2011. TBSS identified a large cluster (threshold p<0·001), where controls showed significant fractional anisotropy (FA) decrease with ageing and alcohol-dependent individuals had significantly lower FA than controls regardless of age. Over the examination interval, 27 (57%) alcohol-dependent individuals abstained, ten (21%) relapsed into light drinking, and ten (21%) relapsed into heavy drinking (>5 kg of alcohol/year). Despite abnormally low FA, age trajectories of the abstainers were positive and progressing toward normality, whereas those of the relapsers and controls were negative. Axial diffusivity (lower values indexing myelin integrity) was abnormally high in the total alcohol-dependent group; however, the abstainers' slopes paralleled those of controls, whereas the heavy-drinking relapsers' slopes showed accelerated ageing. Callosal genu and body microstructure but not macrostructure showed untoward alcohol-related effects. Affected projection and association tracts had an anterior and superior neuroanatomical distribution.Return to heavy drinking resulted in accelerating microstructural white matter damage. Despite evidence for damage, alcohol-dependent individuals maintaining sobriety over extended periods showed improvement in brain fibre tract integrity reflective of fibre reorganisation and myelin restoration, indicative of a neural mechanism explaining recovery.US National Institute on Alcohol Abuse and Alcoholism (AA012388, AA017168, AA005965, AA013521-INIA).
View details for DOI 10.1016/S2215-0366(14)70301-3
View details for PubMedID 26360732
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Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled, longitudinal magnetic resonance imaging study.
Neurobiology of aging
2014; 35 (7): 1755-1768
Abstract
Advances in treatment have transformed human immunodeficiency virus (HIV) infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems, including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 magnetic resonance imaging and a battery of neuropsychological tests collected 2 or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; cerebrospinal fluid-filled spaces showed increase in volume for both groups. Although HIV-infected individuals were in good general health, and free of clinically-detectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacologic treatment and control of further infection, has the potential of abating decline in associated higher-order functions, notably, explicit memory, executive functions, self-regulation, and visuospatial abilities.
View details for DOI 10.1016/j.neurobiolaging.2014.01.008
View details for PubMedID 24508219
View details for PubMedCentralID PMC3980003
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Dynamic metabolic imaging of hyperpolarized [2-(13) C]pyruvate using spiral chemical shift imaging with alternating spectral band excitation.
Magnetic resonance in medicine
2014; 71 (6): 2051-2058
Abstract
In contrast to [1-(13) C]pyruvate, hyperpolarized [2-(13) C]pyruvate permits the ability to follow the (13) C label beyond flux through pyruvate dehydrogenase complex and investigate the incorporation of acetyl-coenzyme A into different metabolic pathways. However, chemical shift imaging (CSI) with [2-(13) C]pyruvate is challenging owing to the large spectral dispersion of the resonances, which also leads to severe chemical shift displacement artifacts for slice-selective acquisitions.This study introduces a sequence for three-dimensional CSI of [2-(13) C]pyruvate using spectrally selective excitation of limited frequency bands containing a subset of metabolites. Dynamic CSI data were acquired alternately from multiple frequency bands in phantoms for sequence testing and in vivo in rat heart.Phantom experiments verified the radiofrequency pulse design and demonstrated that the signal behavior of each group of resonances was unaffected by excitation of the other frequency bands. Dynamic three-dimensional (13) C CSI data demonstrated the sequence capability to image pyruvate, lactate, acetylcarnitine, glutamate, and acetoacetate, enabling the analysis of organ-specific spectra and metabolite time courses.The presented method allows CSI of widely separated resonances without chemical shift displacement artifact, acquiring multiple frequency bands alternately to obtain dynamic time-course information. This approach enables robust imaging of downstream metabolic products of acetyl-coenzyme A with hyperpolarized [2-(13) C]pyruvate. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc.
View details for DOI 10.1002/mrm.24871
View details for PubMedID 23878057
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Dissociation of preparatory attention and response monitoring maturation during adolescence.
Clinical neurophysiology
2014; 125 (5): 962-970
Abstract
Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound "bottom-up" to more mature executive-driven "top-down" processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN).CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11-18 years, using a variation of a letter discrimination task.Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied.The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring.This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes.
View details for DOI 10.1016/j.clinph.2013.10.012
View details for PubMedID 24211003
View details for PubMedCentralID PMC3981931
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Synchrony of anterior cingulate cortex and insular-striatal activation predicts ambiguity aversion in individuals with low impulsivity.
Cerebral cortex
2014; 24 (5): 1397-1408
Abstract
Personal attitude toward ambiguity contributes to individual differences in decision making in uncertain situations. Operationally, these attitudes reflect the various coping strategies elected to overcome the limited information. A key brain region involved in cognitive control for performance adjustments is the dorsal anterior cingulate cortex (dACC). To test how dACC functional network connectivity would be modulated by uncertainty and differ between individuals, 24 healthy participants underwent functional MRI in 3 sequential runs: 1 resting-state and 2 decision-making task runs. Individuals with lower nonplanning impulsiveness made greater use of a Pass option and avoided uncertain ambiguous situations. Seed-based functional connectivity analysis during the task runs revealed that stronger activation synchrony between the left dACC and the right anterior insula correlated with greater use of a Pass response option. During the resting-state, stronger resting-state functional connectivity between the left dACC and the ventral striatum predicted the adoption of Pass as a behavioral strategy and correlated with stronger task-activated synchrony between the dACC and the right anterior insula. Our findings indicate that that the synchrony between the dACC and insula-striatal circuitry was greater in individuals with low compared with high nonplanning impulsiveness and contributed to adopting Pass as a useful behavioral strategy.
View details for DOI 10.1093/cercor/bht008
View details for PubMedID 23355606
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Monkeys that Voluntarily and Chronically Drink Alcohol Damage their Brains: a Longitudinal MRI Study.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2014; 39 (4): 823-830
Abstract
Neuroimaging has consistently documented reductions in the brain tissue of alcoholics. Inability to control comorbidity, environmental insult, and nutritional deficiency, however, confound the ability to assess whether ethanol itself is neurotoxic. Here we report monkey oral ethanol self-administration combined with MR imaging to characterize brain changes over 15 months in 18 well-nourished rhesus macaques. Significant brain volume shrinkage occurred in the cerebral cortices of monkeys drinking3 g/kg ethanol/day (12 alcoholic drinks) at 6 months, and this persisted throughout the period of continuous access to ethanol. Correlation analyses revealed a cerebral cortical volumetric loss of ∼0.11% of the intracranial vault for each daily drink (0.25 g/kg), and selective vulnerability of cortical and non-cortical brain regions. These results demonstrate for the first time a direct relation between oral ethanol intake and measures of decreased brain gray matter volume in vivo in primates. Notably, greater volume shrinkage occurred in monkeys with younger drinking onset that ultimately became heavier drinkers than monkeys with older drinking onset. The pattern of volumetric changes observed in nonhuman primates following 15 months of drinking suggests that cerebral cortical gray matter changes are the first macroscopic manifestation of chronic ethanol exposure in the brain.
View details for DOI 10.1038/npp.2013.259
View details for PubMedID 24077067
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Rat strain differences in brain structure and neurochemistry in response to binge alcohol
PSYCHOPHARMACOLOGY
2014; 231 (2): 429-445
Abstract
Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)).Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment.The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain.As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats.The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.
View details for DOI 10.1007/s00213-013-3253-z
View details for Web of Science ID 000329321700013
View details for PubMedID 24030467
View details for PubMedCentralID PMC3904647
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In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-(13) C] and [2-(13) C]pyruvate.
NMR in biomedicine
2013; 26 (12): 1680-1687
Abstract
Hyperpolarized (13) C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-(13) C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in (13) C-bicarbonate production after dichloroacetate (DCA) administration. With [1-(13) C]pyruvate, the (13) C label is released as (13) CO2 /(13) C-bicarbonate, and, hence, does not allow us to follow the fate of acetyl-CoA. Pyruvate labeled in the C2 position has been used to track the (13) C label into the TCA (tricarboxylic acid) cycle and measure [5-(13) C]glutamate as well as study changes in [1-(13) C]acetylcarnitine with DCA and dobutamine. This work investigates changes in the metabolic fate of acetyl-CoA in response to metabolic interventions of DCA-induced increased PDC flux in the fed and fasted state, and increased cardiac workload with dobutamine in vivo in rat heart at two different pyruvate doses. DCA led to a modest increase in the (13) C labeling of [5-(13) C]glutamate, and a considerable increase in [1-(13) C]acetylcarnitine and [1,3-(13) C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-(13) C]lactate, [2-(13) C]alanine and [5-(13) C]glutamate. The change in glutamate with dobutamine was observed using a high pyruvate dose but not with a low dose. The relative changes in the different metabolic products provide information about the relationship between PDC-mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways. Using a high dose of pyruvate may provide an improved ability to observe changes in glutamate. Copyright © 2013 John Wiley & Sons, Ltd.
View details for DOI 10.1002/nbm.3003
View details for PubMedID 23904148
View details for PubMedCentralID PMC3838505
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A selective insular perfusion deficit contributes to compromised salience network connectivity in recovering alcoholic men.
Biological psychiatry
2013; 74 (7): 547-555
Abstract
BACKGROUND: Alcoholism can disrupt neural synchrony between nodes of intrinsic functional networks that are maximally active when resting relative to engaging in a task, the default mode network (DMN) pattern. Untested, however, are whether the DMN in alcoholics can rebound normally from the relatively depressed task state to the active resting state and whether local perfusion deficits could disrupt network synchrony when switching from conditions of rest to task to rest, thereby indicating a physiological mechanism of neural network adaptation capability. METHODS: Whole-brain, three-dimensional pulsed-continuous arterial spin labeling provided measurements of regional cerebral blood flow (CBF) in 12 alcoholics and 12 control subjects under three conditions: pretask rest, spatial working-memory task, and posttask rest. RESULTS: With practice, alcoholics and control subjects achieved similar task accuracy and reaction times. Both groups exhibited a high-low-high pattern of perfusion levels in DMN regions during the rest-task-rest runs and the opposite pattern in posterior and cerebellar regions known to be associated with spatial working memory. Alcoholics showed selective differences from control subjects in the rest-task-rest CBF pattern in the anterior precuneus and CBF level in the insula, a hub of the salience network. Connectivity analysis identified activation synchrony from an insula seed to salience nodes (parietal, medial frontal, anterior cingulate cortices) in control subjects only. CONCLUSIONS: We propose that attenuated insular CBF is a mechanism underlying compromised connectivity among salience network nodes. This local perfusion deficit in alcoholics has the potential to impair ability to switch from cognitive states of interoceptive cravings to cognitive control for curbing internal urges.
View details for DOI 10.1016/j.biopsych.2013.02.026
View details for PubMedID 23587427
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Exchange-Linked Dissolution Agents in Dissolution-DNP C-13 Metabolic Imaging
MAGNETIC RESONANCE IN MEDICINE
2013; 70 (4): 936-942
Abstract
PURPOSE: The use of unlabeled exchange-linked dissolution agents in hyperpolarized metabolic imaging was studied to examine pool size limits and saturation relative to the availability of NADH. METHODS: Three-dimensional dynamic metabolic images were obtained, and compared following injection of a bolus of hyperpolarized [1-(13) C]pyruvate, prepared with and without unlabeled sodium lactate in the dissolution buffer. Comparisons were made on the basis of apparent rate constants and [1-(13) C]lactate signal-to-noise ratio. Range finding data were obtained for different bolus compositions. Isotope exchange was also probed in the reverse direction, following injection of a bolus of hyperpolarized [1-(13) C]lactate, with and without unlabeled sodium pyruvate in the dissolution buffer. RESULTS: Liver, kidney, and vascular regions of interest all showed an increase in [1-(13) C]lactate signal with addition of unlabeled sodium lactate in the dissolution buffer. Injection of hyperpolarized [1-(13) C]lactate with unlabeled sodium pyruvate in the dissolution buffer, provided exchange rate constants K(lp) for kidney and vascular regions of interest. CONCLUSIONS: These results are consistent with a high level of (13) C-exchange, and with labeling rates that are limited by steady-state pool sizes in vivo. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
View details for DOI 10.1002/mrm.24544
View details for Web of Science ID 000325136300005
View details for PubMedCentralID PMC3660543
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Effects of Isoflurane Anesthesia on Hyperpolarized C-13 Metabolic Measurements in Rat Brain
MAGNETIC RESONANCE IN MEDICINE
2013; 70 (4): 1117-1124
Abstract
PURPOSE: Commonly used anesthetic agents such as isoflurane are known to be potent cerebral vasodilators, with reported dose-dependent increase in cerebral blood flow and cerebral blood volume. Despite the widespread use of isoflurane in hyperpolarized (13) C preclinical research studies, a quantitative assessment of its effect on metabolic measurements is limited. This work investigates the effect of isoflurane anesthesia dose on hyperpolarized (13) C MR metabolic measurements in rat brain for [1-(13) C]pyruvate and 2-keto[1-(13) C]isocaproate. METHODS: Dynamic 2D and 3D spiral chemical shift imaging was used to acquire metabolic images of rat brain as well as kidney and liver following bolus injections of hyperpolarized [1-(13) C]pyruvate or 2-keto[1-(13) C]isocaproate. The impact of a "low dose" vs. a "high dose" of isoflurane on cerebral metabolite levels and apparent conversion rates was examined. RESULTS: The cerebral substrate signal levels, and hence the metabolite-to-substrate ratios and apparent conversion rates, were found to depend markedly on isoflurane dose, while signal levels of metabolic products and their ratios, e.g. bicarbonate/lactate, were largely insensitive to isoflurane levels. No obvious dependence on isoflurane was observed in kidney or liver for pyruvate. CONCLUSION: This study highlights the importance of careful attention to the effects of anesthesia on the metabolic measures for hyperpolarized (13) C metabolic imaging in brain. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
View details for DOI 10.1002/mrm.24532
View details for Web of Science ID 000325136300023
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Effects of isoflurane anesthesia on hyperpolarized (13)C metabolic measurements in rat brain.
Magnetic resonance in medicine
2013; 70 (4): 1117-1124
Abstract
PURPOSE: Commonly used anesthetic agents such as isoflurane are known to be potent cerebral vasodilators, with reported dose-dependent increase in cerebral blood flow and cerebral blood volume. Despite the widespread use of isoflurane in hyperpolarized (13) C preclinical research studies, a quantitative assessment of its effect on metabolic measurements is limited. This work investigates the effect of isoflurane anesthesia dose on hyperpolarized (13) C MR metabolic measurements in rat brain for [1-(13) C]pyruvate and 2-keto[1-(13) C]isocaproate. METHODS: Dynamic 2D and 3D spiral chemical shift imaging was used to acquire metabolic images of rat brain as well as kidney and liver following bolus injections of hyperpolarized [1-(13) C]pyruvate or 2-keto[1-(13) C]isocaproate. The impact of a "low dose" vs. a "high dose" of isoflurane on cerebral metabolite levels and apparent conversion rates was examined. RESULTS: The cerebral substrate signal levels, and hence the metabolite-to-substrate ratios and apparent conversion rates, were found to depend markedly on isoflurane dose, while signal levels of metabolic products and their ratios, e.g. bicarbonate/lactate, were largely insensitive to isoflurane levels. No obvious dependence on isoflurane was observed in kidney or liver for pyruvate. CONCLUSION: This study highlights the importance of careful attention to the effects of anesthesia on the metabolic measures for hyperpolarized (13) C metabolic imaging in brain. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
View details for DOI 10.1002/mrm.24532
View details for PubMedID 23086864
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Midbrain-driven emotion and reward processing in alcoholism.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2013; 38 (10): 1844-1853
Abstract
Alcohol dependence is associated with impaired control over emotionally motivated actions, possibly associated with abnormalities in the frontoparietal executive control network and midbrain nodes of the reward network associated with automatic attention. To identify differences in the neural response to alcohol-related word stimuli, 26 chronic alcoholics (ALC) and 26 healthy controls (CTL) performed an alcohol-emotion Stroop Match-to-Sample task during functional MR imaging. Stroop contrasts were modeled for color-word incongruency (eg, word RED printed in green) and for alcohol (eg, BEER), positive (eg, HAPPY) and negative (eg, MAD) emotional word content relative to congruent word conditions (eg, word RED printed in red). During color-Stroop processing, ALC and CTL showed similar left dorsolateral prefrontal activation, and CTL, but not ALC, deactivated posterior cingulate cortex/cuneus. An interaction revealed a dissociation between alcohol-word and color-word Stroop processing: ALC activated midbrain and parahippocampal regions more than CTL when processing alcohol-word relative to color-word conditions. In ALC, the midbrain region was also invoked by negative emotional Stroop words thereby showing significant overlap of this midbrain activation for alcohol-related and negative emotional processing. Enhanced midbrain activation to alcohol-related words suggests neuroadaptation of dopaminergic midbrain systems. We speculate that such tuning is normally associated with behavioral conditioning to optimize responses but here contributed to automatic bias to alcohol-related stimuli.Neuropsychopharmacology advance online publication, 29 May 2013; doi:10.1038/npp.2013.102.
View details for DOI 10.1038/npp.2013.102
View details for PubMedID 23615665
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Midbrain-Driven Emotion and Reward Processing in Alcoholism
NEUROPSYCHOPHARMACOLOGY
2013; 38 (10): 1844-1853
View details for DOI 10.1038/npp.2013.102
View details for Web of Science ID 000323165500002
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Fiber tract-driven topographical mapping (FTTM) reveals microstructural relevance for interhemispheric visuomotor function in the aging brain.
NeuroImage
2013; 77: 195-206
Abstract
We present a novel approach - DTI-based fiber tract-driven topographical mapping (FTTM) - to map and measure the influence of age on the integrity of interhemispheric fibers and challenge their selective functions with measures of interhemispheric integration of lateralized information. This approach enabled identification of spatially specific topographical maps of scalar diffusion measures and their relation to measures of visuomotor performance. Relative to younger adults, older adults showed lower fiber integrity indices in anterior than posterior callosal fibers. FTTM analysis identified a dissociation in the microstructural-function associates between age groups: in younger adults, genu fiber integrity correlated with interhemispheric transfer time, whereas in older adults, body fiber integrity was correlated with interhemispheric transfer time with topographical specificity along left-lateralized callosal fiber trajectories. Neural co-activation from redundant targets was evidenced by fMRI-derived bilateral extrastriate cortex activation in both groups, and a group difference emerged for a pontine activation cluster that was differently modulated by response hand in older than younger adults. Bilateral processing advantages in older but not younger adults further correlated with fiber integrity in transverse pontine fibers that branch into the right cerebellar cortex, thereby supporting a role for the pons in interhemispheric facilitation. In conclusion, in the face of compromised anterior callosal fibers, older adults appear to use alternative pathways to accomplish visuomotor interhemispheric information transfer and integration for lateralized processing. This shift from youthful associations may indicate recruitment of compensatory mechanisms involving medial corpus callosum fibers and subcortical pathways.
View details for DOI 10.1016/j.neuroimage.2013.03.056
View details for PubMedID 23567886
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In vivo measurement of aldehyde dehydrogenase-2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1-(13) C]pyruvate.
NMR in biomedicine
2013; 26 (6): 607-612
Abstract
To date, measurements of the activity of aldehyde dehydrogenase-2 (ALDH2), a critical mitochondrial enzyme for the elimination of certain cytotoxic aldehydes in the body and a promising target for drug development, have been largely limited to in vitro methods. Recent advancements in MRS of hyperpolarized (13) C-labeled substrates have provided a method to detect and image in vivo metabolic pathways with signal-to-noise ratio gains greater than 10 000-fold over conventional MRS techniques. However aldehydes, because of their toxicity and short T1 relaxation times, are generally poor targets for such (13) C-labeled studies. In this work, we show that dynamic MRSI of hyperpolarized [1-(13) C]pyruvate and its conversion to [1-(13) C]lactate can provide an indirect in vivo measurement of ALDH2 activity via the concentration of NADH (nicotinamide adenine dinucleotide, reduced form), a co-factor common to both the reduction of pyruvate to lactate and the oxidation of acetaldehyde to acetate. Results from a rat liver ethanol model (n = 9) show that changes in (13) C-lactate labeling following the bolus injection of hyperpolarized pyruvate are highly correlated with changes in ALDH2 activity (R(2) = 0.76). Copyright © 2012 John Wiley & Sons, Ltd.
View details for DOI 10.1002/nbm.2897
View details for PubMedID 23225495
View details for PubMedCentralID PMC3634870
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INTRINSIC FUNCTIONAL CONNECTIVITY IN ALCOHOLISM: TEST-RETEST STABILITY AND NORMALIZATION WITH SOBRIETY
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 212A–212A
View details for Web of Science ID 000318998300806
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WERNICKE-KORSAKOFF SYNDROME: A NUTRITIONAL ALCOHOL-RELATED BRAIN DISORDER
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 254A–254A
View details for Web of Science ID 000318998301158
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DECISION-MAKINGAND BRAIN STRUCTURAL SUBSTRATES IN ALCOHOLISM, HIV INFECTION, AND THEIR COMORBIDITY
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 113A–113A
View details for Web of Science ID 000318998300411
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ANIMAL MODELS OF ALCOHOLISM AND COMMON CONCOMITANTS OF ALCOHOLISM: BASIS FOR INTERPRETATION OF FINDINGS IN HUMAN STUDIES
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 119A–119A
View details for Web of Science ID 000318998300436
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LONGITUDINAL CHANGES IN SLEEP EEG AND BRAIN STRUCTURE IN ADOLESCENCE
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 278A–278A
View details for Web of Science ID 000318998301252
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DIFFERENTIAL IMPROVEMENT IN NEUROCOGNITION WITH GREATER ANTIRETROVIRAL CNS PENETRATION EFFECTIVENESS IN ALCOHOLISM-HIV INFECTION COMORBIDITY
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 27A–27A
View details for Web of Science ID 000318998300068
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Modulation of limbic-cerebellar functional connectivity enables alcoholics to recognize who is who.
Brain structure & function
2013; 218 (3): 683-695
Abstract
Chronic alcoholism is known to disrupt functions served by distributed brain systems, including limbic and frontocerebellar circuits involved in resting-state and task-activated networks subserving component processes of memory often affected in alcoholics. Using an fMRI paradigm, we investigated whether memory performance by alcoholics on a face-name association test previously observed to be problematic for alcoholics could be explained by desynchronous activity between nodes of these specific networks. While in the scanner, 18 alcoholics and 15 controls performed a face-name associative learning task with different levels of processing at encoding. This task was designed to activate the hippocampus, cerebellum, and frontal cortex. Alcoholics and controls were also scanned at rest. Twelve alcoholics and 12 controls were selected to be matched on face-name recognition performance. Task-related fMRI analysis indicated that alcoholics had preserved limbic activation but lower cerebellar activation (Crus II) than the controls in the face-name learning task. Crus II was, therefore, chosen as a seed for functional connectivity MRI analysis. At rest, the left hippocampus and left Crus II had positively synchronized activity in controls, while hippocampal and cerebellar activities were negatively synchronized in alcoholics. Task engagement resulted in hippocampal-cerebellar desynchronization in both groups. We speculate that atypical cerebello-hippocampal activity synchronization during rest in alcoholics was reset to the normal pattern of asynchrony by task engagement. Aberrations from the normal pattern of resting-state default mode synchrony could be interpreted as enabling preserved face-name associative memory in alcoholism.
View details for DOI 10.1007/s00429-012-0421-6
View details for PubMedID 22585315
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Modulation of limbic-cerebellar functional connectivity enables alcoholics to recognize who is who
BRAIN STRUCTURE & FUNCTION
2013; 218 (3): 683-695
View details for DOI 10.1007/s00429-012-0421-6
View details for Web of Science ID 000318310600005
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A Mechanism of Rapidly Reversible Cerebral Ventricular Enlargement Independent of Tissue Atrophy
NEUROPSYCHOPHARMACOLOGY
2013; 38 (6): 1121-1129
View details for DOI 10.1038/npp.2013.11
View details for Web of Science ID 000317584600023
View details for PubMedID 23306181
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A mechanism of rapidly reversible cerebral ventricular enlargement independent of tissue atrophy.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
2013; 38 (6): 1121-1129
Abstract
Ventricular enlargement, a common in vivo marker of aging, disease, and insult, is presumed to reflect atrophy of surrounding brain regions. Pathological mechanisms underlying ventricular enlargement, however, are likely specific to the condition under investigation. Here, multimodal imaging, incorporating structural magnetic resonance imaging (MRI), MR spectroscopy (MRS), and diffusion weighted imaging (DWI), was used in rats exposed to binge ethanol (EtOH) to provide insight into a mechanism of reversible ventricular enlargement. During intoxication, MRI revealed expansion of ventricles, but volume changes in dorsal or ventral hippocampi, caudate-putamen, or thalamus were not detectible. MRS of whole-brain parenchyma showed decreases in N-acetylasparate (NAA) and tissue water T2, and increases in choline-containing compounds (Cho). DWI showed decreased diffusivity selective to the thalamus. All MR parameters returned to baseline with 7 days of recovery. Rapid recovery of ventricular volume and the absence of detectable tissue volume reductions in brain regions adjacent to ventricles argue against atrophy as a mechanism of ventricular expansion. Decreased tissue water T2 and decreased thalamic diffusivity suggest lower tissue water content and a role for both NAA and Cho, as osmolytes is proposed. Together, these data support a model of fluid redistribution during acute EtOH intoxication and recovery to account for rapid ventricular volume changes.
View details for DOI 10.1038/npp.2013.11
View details for PubMedID 23306181
View details for PubMedCentralID PMC3629396
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In vivo glutamate measured with magnetic resonance spectroscopy: behavioral correlates in aging
NEUROBIOLOGY OF AGING
2013; 34 (4): 1265-1276
Abstract
Altered availability of the brain biochemical glutamate might contribute to the neural mechanisms underlying age-related changes in cognitive and motor functions. To investigate the contribution of regional glutamate levels to behavior in the aging brain, we used an in vivo magnetic resonance spectroscopy protocol optimized for glutamate detection in 3 brain regions targeted by cortical glutamatergic efferents-striatum, cerebellum, and pons. Data from 61 healthy men and women ranging in age from 20 to 86 years were used. Older age was associated with lower glutamate levels in the striatum, but not cerebellum or pons. Older age was also predictive of poorer performance on tests of visuomotor skills and balance. Low striatal glutamate levels were associated with high systolic blood pressure and worse performance on a complex visuomotor task, the Grooved Pegboard. These findings suggest that low brain glutamate levels are related to high blood pressure and that changes in brain glutamate levels might mediate the behavioral changes noted in normal aging.
View details for DOI 10.1016/j.neurobiolaging.2012.09.014
View details for Web of Science ID 000314708000027
View details for PubMedID 23116877
View details for PubMedCentralID PMC3545108
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Quantification of glutamate and glutamine using constant-time point-resolved spectroscopy at 3 T
NMR IN BIOMEDICINE
2013; 26 (2): 164-172
Abstract
Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant-time point-resolved spectroscopy (CT-PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time-domain basis set was constructed taking into account metabolite T(2) relaxation times and dephasing from B(0) inhomogeneity. Metabolite concentrations were estimated by fitting the basis one-dimensional CT-PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom-built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol-treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol-exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time.
View details for DOI 10.1002/nbm.2831
View details for Web of Science ID 000313886500007
View details for PubMedID 22761057
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Variation in longitudinal trajectories of regional brain volumes of healthy men and women (ages 10 to 85 years) measured with atlas-based parcellation of MRI
NEUROIMAGE
2013; 65: 176-193
Abstract
Numerous cross-sectional MRI studies have characterized age-related differences in regional brain volumes that differ with structure and tissue type. The extent to which cross-sectional assumptions about change are accurate depictions of actual longitudinal measurement remains controversial. Even longitudinal studies can be limited by the age range of participants, sex distribution of the samples, and scan intervals. To address these issues, we calculated trajectories of regional brain volume changes from T1-weighted (SPGR) MRI data, quantified with our automated, unsupervised SRI24 atlas-based registration and parcellation method. Longitudinal MRIs were acquired at 3T in 17 boys and 12 girls, age 10 to 14 years, and 41 men and 41 women, age 20 to 85 years at first scan. Application of a regression-based correction function permitted merging of data acquired at 3T field strength with data acquired at 1.5T from additional subjects, thereby expanding the sample to a total of 55 men and 67 women, age 20 to 85 years at first scan. Adjustment for individual supratentorial volume removed regional volume differences between men and women due to sex-related differences in head size. Individual trajectories were computed from data collected on 2 to 6 MRIs at a single field strength over a ~1 to 8 year interval. Using linear mixed-effects models, the pattern of trajectories over age indicated: rises in ventricular and Sylvian fissure volumes, with older individuals showing faster increases than younger ones; declines in selective cortical volumes with faster tissue shrinkage in older than younger individuals; little effect of aging on volume of the corpus callosum; more rapid expansion of CSF-filled spaces in men than women after age 60 years; and evidence for continued growth in central white matter through early adulthood with accelerated decline in senescence greater in men than women.
View details for DOI 10.1016/j.neuroimage.2012.10.008
View details for Web of Science ID 000312283900016
View details for PubMedID 23063452
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Remapping the brain to compensate for impairment in recovering alcoholics.
Cerebral cortex
2013; 23 (1): 97-104
Abstract
Abnormal brain activity may reflect compensation when observed in patients who perform normally on tests requiring functions usually observed as impaired. Operational criteria defining compensation have been described and aid in distinguishing compensatory from chance events. Here, we tested whether previously published functional magnetic resonance imaging data acquired in 15 recovering alcoholics and 15 controls at rest and while performing a spatial working memory task would fulfill criteria defining functional compensation. Multivariate analysis tested how well abnormal activation in the affected group predicted normal performance, despite low or no activation in brain regions invoked by controls to accomplish the same task. By identifying networks that uniquely and positively correlated with good performance, we provide evidence for compensatory recruitment of cerebellar-based functional networks by alcoholics. Whereas controls recruited prefrontal-cerebellar regions VI/Crus I known to subserve working memory, alcoholics recruited 2 other parallel frontocerebellar loops: dorsolateral prefrontal cortex (DLPFC)-cerebellar VIII system during rest and DLPFC-cerebellar VI system while task engaged. Greater synchronous activity between cerebellar lobule VIII and DLPFC at rest and greater activation within cerebellar lobule VI and DLPFC during task predicted better working memory performance. Thus, higher intrinsic cerebellar activity in alcoholics was an adequate condition for triggering task-relevant activity in the frontal cortex required for normal working memory performance.
View details for DOI 10.1093/cercor/bhr381
View details for PubMedID 22275479
View details for PubMedCentralID PMC3513953
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Visual Search and the Aging Brain: Discerning the Effects of Age-Related Brain Volume Shrinkage on Alertness, Feature Binding, and Attentional Control
NEUROPSYCHOLOGY
2013; 27 (1): 48-59
View details for DOI 10.1037/a0030921
View details for Web of Science ID 000313757200006
View details for PubMedID 23356596
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Remapping the Brain to Compensate for Impairment in Recovering Alcoholics
CEREBRAL CORTEX
2013; 23 (1): 97-104
View details for DOI 10.1093/cercor/bhr381
View details for Web of Science ID 000312106300010
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Visual search and the aging brain: discerning the effects of age-related brain volume shrinkage on alertness, feature binding, and attentional control.
Neuropsychology
2013; 27 (1): 48-59
Abstract
Decline in visuospatial abilities with advancing age has been attributed to a demise of bottom-up and top-down functions involving sensory processing, selective attention, and executive control. These functions may be differentially affected by age-related volume shrinkage of subcortical and cortical nodes subserving the dorsal and ventral processing streams and the corpus callosum mediating interhemispheric information exchange.Fifty-five healthy adults (25-84 years) underwent structural MRI and performed a visual search task to test perceptual and attentional demands by combining feature-conjunction searches with "gestalt" grouping and attentional cueing paradigms.Poorer conjunction, but not feature, search performance was related to older age and volume shrinkage of nodes in the dorsolateral processing stream. When displays allowed perceptual grouping through distractor homogeneity, poorer conjunction-search performance correlated with smaller ventrolateral prefrontal cortical and callosal volumes. An alerting cue attenuated age effects on conjunction search, and the alertness benefit was associated with thalamic, callosal, and temporal cortex volumes.Our results indicate that older adults can capitalize on early parallel stages of visual information processing, whereas age-related limitations arise at later serial processing stages requiring self-guided selective attention and executive control. These limitations are explained in part by age-related brain volume shrinkage and can be mitigated by external cues.
View details for DOI 10.1037/a0030921
View details for PubMedID 23356596
View details for PubMedCentralID PMC3718286
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White matter fiber compromise contributes differentially to attention and emotion processing impairment in alcoholism, HIV-infection, and their comorbidity
NEUROPSYCHOLOGIA
2012; 50 (12): 2812-2822
Abstract
Alcoholism (ALC) and HIV-1 infection (HIV) each affects emotional and attentional processes and integrity of brain white matter fibers likely contributing to functional compromise. The highly prevalent ALC+HIV comorbidity may exacerbate compromise. We used diffusion tensor imaging (DTI) and an emotional Stroop Match-to-Sample task in 19 ALC, 16 HIV, 15 ALC+HIV, and 15 control participants to investigate whether disruption of fiber system integrity accounts for compromised attentional and emotional processing. The task required matching a cue color to that of an emotional word with faces appearing between the color cue and the Stroop word in half of the trials. Nonmatched cue-word color pairs assessed selective attention, and face-word pairs assessed emotion. Relative to controls, DTI-based fiber tracking revealed lower inferior longitudinal fasciculus (ilf) integrity in HIV and ALC+HIV and lower uncinate fasciculus (uf) integrity in all three patient groups. Controls exhibited Stroop effects to positive face-word emotion, and greater interference was related to greater callosal, cingulum and ilf integrity. By contrast, HIV showed greater interference from negative Stroop words during color-nonmatch trials, correlating with greater uf compromise. For face trials, ALC and ALC+HIV showed greater Stroop-word interference, correlating with lower cingulate and callosal integrity. Thus, in HIV, conflict resolution was diminished when challenging conditions usurped resources needed to manage interference from negative emotion and to disengage attention from wrongly cued colors (nonmatch). In ALC and ALC+HIV, poorer callosal integrity was related to enhanced emotional interference suggesting curtailed interhemispheric exchange needed between preferentially right-hemispheric emotion and left-hemispheric Stroop-word functions.
View details for DOI 10.1016/j.neuropsychologia.2012.07.042
View details for Web of Science ID 000310945900012
View details for PubMedID 22960416
View details for PubMedCentralID PMC3473169
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Application of hyperpolarized [1-13C]lactate for the in vivo investigation of cardiac metabolism
NMR IN BIOMEDICINE
2012; 25 (10): 1119-1124
Abstract
In addition to cancer imaging, (13) C-MRS of hyperpolarized pyruvate has also demonstrated utility for the investigation of cardiac metabolism and ischemic heart disease. Although no adverse effects have yet been reported for doses commonly used in vivo, high substrate concentrations have lead to supraphysiological pyruvate levels that can affect the underlying metabolism and should be considered when interpreting results. With lactate serving as an important energy source for the heart and physiological lactate levels one to two orders of magnitude higher than for pyruvate, hyperpolarized lactate could potentially be used as an alternative to pyruvate for probing cardiac metabolism. In this study, hyperpolarized [1-(13) C]lactate was used to acquire time-resolved spectra from the healthy rat heart in vivo and to measure dichloroacetate (DCA)-modulated changes in flux through pyruvate dehydrogenase (PDH). Both primary oxidation of lactate to pyruvate and subsequent conversion of pyruvate to alanine and bicarbonate could reliably be detected. Since DCA stimulates the activity of PDH through inhibition of PDH kinase, a more than 2.5-fold increase in bicarbonate-to-substrate ratio was found after administration of DCA, similar to the effect when using [1-(13) C]pyruvate as the substrate.
View details for DOI 10.1002/nbm.2778
View details for Web of Science ID 000308710400003
View details for PubMedID 22278751
View details for PubMedCentralID PMC3357452
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Differential Effect of Alcoholism and HIV Infection on Visuomotor Procedural Learning and Retention
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2012; 36 (10): 1738-1747
Abstract
Selective declarative memory processes are differentially compromised in chronic alcoholism (ALC) and HIV infection (HIV) and likely reflect neuropathology associated with each condition: frontocerebellar dysfunction in ALC and frontostriatal dysfunction in HIV infection. Evidence for disease overlap derives from observed exacerbated impairments in these declarative memory processes in ALC-HIV comorbidity. Less is known about nondeclarative memory processes in these disease conditions. Examination of visuomotor learning in chronic ALC and HIV infection could provide insight into the differential and combined contribution of selective disease-related injury to visuomotor procedural memory processes.We examined component processes of visuomotor learning and retention on the rotary pursuit task in 29 ALC, 23 HIV, 28 ALC + HIV, and 20 control subjects. Participants were given 4 rotary pursuit learning sessions over 2 testing days, typically separated by 1 week, to assess visuomotor learning and retention patterns. Ancillary measures of simple motor, psychomotor, explicit memory, and balance abilities were administered to test which component processes independently predicted visuomotor learning.All clinical groups showed visuomotor learning across rotary pursuit testing sessions, despite impairment in visuomotor speed in the HIV groups and impairment in explicit memory and psychomotor speed in the alcohol groups. The 2 alcoholic groups showed retention and consolidation over time (i.e., improved performance without further training), whereas the HIV-infected group showed learning and retention but no consolidation effect. The comorbid group shared impairments associated with the ALC-only group (explicit memory and psychomotor speed) and the HIV-only group (visuomotor speed), although there was no clear compounded effect of alcohol and HIV infection on visuomotor learning performance.This study supports the hypothesis that ALC and HIV infection exert differential effects on components of visuomotor procedural learning. Further, the results provide behavioral evidence for dissociable influences of frontocerebellar and frontostriatal disruption to visuomotor procedural learning and retention.
View details for DOI 10.1111/j.1530-0277.2012.01790.x
View details for Web of Science ID 000309390800009
View details for PubMedID 22823125
View details for PubMedCentralID PMC3463647
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Selective neurocognitive deficits and poor life functioning are associated with significant depressive symptoms in alcoholism-HIV infection comorbidity
PSYCHIATRY RESEARCH
2012; 199 (2): 102-110
Abstract
Alcoholism, HIV, and depressive symptoms frequently co-occur and are associated with impairment in cognition and life function. We administered the Beck Depression Inventory-II (BDI-II), measures of life function, and neurocognitive tests to 67 alcoholics, 56 HIV+ patients, 63 HIV+ alcoholics, and 64 controls to examine whether current depressive symptom level (significant, BDI-II>14 vs. minimal, BDI-II<14) was associated with poorer cognitive or psychosocial function in alcoholism-HIV comorbidity. Participants with significant depressive symptoms demonstrated slower manual motor speed and poorer visuospatial memory than those with minimal depressive symptoms. HIV patients with depressive symptoms showed impaired manual motor speed. Alcoholics with depressive symptoms showed impaired visuospatial memory. HIV+ alcoholics with depressive symptoms reported the poorest quality of life; alcoholics with depressive symptoms, irrespective of HIV status, had poorest life functioning. Thus, significant depressive symptoms were associated with poorer selective cognitive and life functioning in alcoholism and in HIV infection, even though depressive symptoms had neither synergistic nor additive effects on cognition in alcoholism-HIV comorbidity. The results suggest the relevance of assessing and treating current depressive symptoms to reduce cognitive compromise and functional disability in HIV infection, alcoholism, and their comorbidity.
View details for DOI 10.1016/j.psychres.2012.05.009
View details for Web of Science ID 000312510700005
View details for PubMedID 22648011
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Regional Brain Structural Dysmorphology in Human Immunodeficiency Virus Infection: Effects of Acquired Immune Deficiency Syndrome, Alcoholism, and Age
BIOLOGICAL PSYCHIATRY
2012; 72 (5): 361-370
Abstract
Human immunodeficiency virus (HIV) infection and alcoholism each carries liability for disruption of brain structure and function integrity. Despite considerable prevalence of HIV-alcoholism comorbidity, few studies examined the potentially heightened burden of disease comorbidity.Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65 with HIV infection and alcoholism, and 108 healthy control subjects. This design enabled examination of independent and combined effects of HIV infection and alcoholism along with other factors (acquired immune deficiency syndrome [AIDS]-defining events, hepatitis C infection, age) on regional brain volumes derived from T1-weighted magnetic resonance images.Brain volumes, expressed as Z scores corrected for intracranial volume and age, were measured in 20 tissue and 5 ventricular and sulcal regions. The most profound and consistent volume deficits occurred with alcohol use disorders, notable in the cortical mantle, insular and anterior cingulate cortices, thalamus, corpus callosum, and frontal sulci. The HIV-only group had smaller thalamic and larger frontal sulcal volumes than control subjects. HIV disease-related factors associated with greater volume abnormalities included CD4 cell count nadir, clinical staging, history of AIDS-defining events, infection age, and current age. Longer sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities in both alcohol groups.Having HIV infection with alcoholism and AIDS had an especially poor outcome on brain structures. That longer periods of sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities encourages the inclusion of alcohol recovery efforts in HIV/AIDS therapeutic settings.
View details for DOI 10.1016/j.biopsych.2012.02.018
View details for Web of Science ID 000307308100006
View details for PubMedID 22458948
View details for PubMedCentralID PMC3393798
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EXACERBATION OF HIV-RELATED NEURODEGRADATION BY SEVERE ALCOHOLISM REVEALED WITH IN VIVO NEUROIMAGING
16th World Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
WILEY-BLACKWELL. 2012: 79A–79A
View details for Web of Science ID 000308396700268
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Fast volumetric imaging of ethanol metabolism in rat liver with hyperpolarized [1-13C]pyruvate
NMR IN BIOMEDICINE
2012; 25 (8): 993-999
Abstract
Rapid volumetric imaging of hyperpolarized (13) C compounds allows the real-time measurement of metabolic activity and can be useful in distinguishing between normal and diseased tissues. This work extends a fast two-dimensional undersampled spiral MRSI sequence to provide volumetric coverage, acquiring a 16 × 16 × 12 matrix with a nominal isotropic resolution of 5 mm in 4.5 s. The rapid acquisition enables a high temporal resolution for dynamic imaging. This dynamic three-dimensional MRSI method was used to investigate hyperpolarized [1-(13) C]pyruvate metabolism modulated by the administration of ethanol in rat liver. A significant increase in the pyruvate to lactate conversion was observed in the liver as a result of the greater availability of NADH (nicotinamide adenine dinucleotide, reduced form) from ethanol metabolism.
View details for DOI 10.1002/nbm.2762
View details for Web of Science ID 000306178400005
View details for PubMedID 22331837
View details for PubMedCentralID PMC3366020
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Face-Name Association Learning and Brain Structural Substrates in Alcoholism
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2012; 36 (7): 1171-1179
Abstract
Associative learning is required for face-name association and is impaired in alcoholism, but the cognitive processes and brain structural components underlying this deficit remain unclear. It is also unknown whether prompting alcoholics to implement a deep level of processing during face-name encoding would enhance performance.Abstinent alcoholics and controls performed a levels-of-processing face-name learning task. Participants indicated whether the face was that of an honest person (deep encoding) or that of a man (shallow encoding). Retrieval was examined using an associative (face-name) recognition task and a single-item (face or name only) recognition task. Participants also underwent 3T structural MRI.Compared with controls, alcoholics had poorer associative and single-item learning and performed at similar levels. Level of processing at encoding had little effect on recognition performance but affected reaction time (RT). Correlations with brain volumes were generally modest and based primarily on RT in alcoholics, where the deeper the processing at encoding, the more restricted the correlations with brain volumes. In alcoholics, longer control task RTs correlated modestly with smaller tissue volumes across several anterior to posterior brain regions; shallow encoding correlated with calcarine and striatal volumes; deep encoding correlated with precuneus and parietal volumes; and associative recognition RT correlated with cerebellar volumes. In controls, poorer associative recognition with deep encoding correlated significantly with smaller volumes of frontal and striatal structures.Despite prompting, alcoholics did not take advantage of encoding memoranda at a deep level to enhance face-name recognition accuracy. Nonetheless, conditions of deeper encoding resulted in faster RTs and more specific relations with regional brain volumes than did shallow encoding. The normal relation between associative recognition and corticostriatal volumes was not present in alcoholics. Rather, their speeded RTs occurred at the expense of accuracy and were related most robustly to cerebellar volumes.
View details for DOI 10.1111/j.1530-0277.2011.01731.x
View details for Web of Science ID 000306219400009
View details for PubMedID 22509954
View details for PubMedCentralID PMC3394892
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COMBINED EFFECTS OF ALCOHOLISM AND HIV-INFECTION ON SELECTIVE COGNITIVE AND MOTOR FUNCTIONS AND THEIR NEURAL SUBSTRATES
35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA)
WILEY-BLACKWELL. 2012: 273A–273A
View details for Web of Science ID 000304806002242
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FUNCTIONAL CONNECTIVITY STRENGTH IN VISUOSPATIAL ATTENTION NETWORKS IN ALCOHOLISM
35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA)
WILEY-BLACKWELL. 2012: 272A–272A
View details for Web of Science ID 000304806002240
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WHITE MATTER FIBER COMPROMISE CONTRIBUTES TO ATTENTIONAL AND EMOTIONAL PROCESSING IMPAIRMENT IN ALCOHOLISM, HIV INFECTION, AND THEIR COMORBIDITY
35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA)
WILEY-BLACKWELL. 2012: 47A–47A
View details for Web of Science ID 000304806000145
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CNS IMMUNE RESPONSE IN RATS WITH LIVER DAMAGE
35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA)
WILEY-BLACKWELL. 2012: 118A–118A
View details for Web of Science ID 000304806001025
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ADAPTING TO UNCERTAIN HIGH-RISK CONDITIONS IN ALCOHOL DEPENDENCE
35th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA)
WILEY-BLACKWELL. 2012: 236A–236A
View details for Web of Science ID 000304806002094
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Combining atlas-based parcellation of regional brain data acquired across scanners at 1.5 T and 3.0 T field strengths
NEUROIMAGE
2012; 60 (2): 940-951
Abstract
Longitudinal brain morphometric studies designed for data acquisition at a single MRI field strength can be seriously limited by system replacements from lower to higher field strength. Merging data across field strengths has not been endorsed for a variety of reasons, yet the ability to combine such data would broaden longitudinal investigations. To determine whether structural T1-weighted MRI data acquired across MR field strengths could be merged, parcellations of archival SPGR data acquired in 114 individuals at 1.5 T and at 3.0 T within 3 weeks of each other were compared. The first set of analyses examined 1) the correspondence between regional tissue volumes derived from data collected at 1.5 T and 3.0 T and 2) whether there were systematic differences for which a correction factor could be determined and applied to improve measurement agreement. Comparability of regional volume determination at 1.5 T and 3.0 T was assessed with intraclass correlation (ICC) computed on volumes derived from the automated and unsupervised SRI24 atlas registration and parcellation method. A second set of analyses measured the reliability of the registration and quantification using the same approach on longitudinal data acquired in 69 healthy adults at a single field strength, 1.5 T, at an interval < 2 years. The mainstay of the analyses was based on the SRI24 method; to examine the potential of merging data across field strengths and across image analysis packages, a secondary set of analyses used FreeSurfer instead of the SRI24 method. For both methods, a regression-based linear correction function significantly improved correspondence. The results indicated high correspondence between most selected cortical, subcortical, and CSF-filled spaces; correspondence was lowest in the globus pallidus, a region rich in iron, which in turn has a considerable field-dependent effect on signal intensity. Thus, the application of a regression-based correction function that improved the correspondence in regional volume estimations argues well for the proposition that selected T1-weighted regional anatomical brain data can be reliably combined across 1.5 T and 3.0 T field strengths with the application of an appropriate correction procedure.
View details for DOI 10.1016/j.neuroimage.2012.01.092
View details for Web of Science ID 000303272300012
View details for PubMedID 22297204
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Neuroimaging in HIV Infection and Alcoholism Co-Morbidity
SPRINGER. 2012: S24–S24
View details for Web of Science ID 000302288800036
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Synchrony of Corticostriatal-Midbrain Activation Enables Normal Inhibitory Control and Conflict Processing in Recovering Alcoholic Men
BIOLOGICAL PSYCHIATRY
2012; 71 (3): 269-278
View details for DOI 10.1016/j.biopsych.2011.10.022
View details for Web of Science ID 000299010900014
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MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping
NEUROIMAGE
2012; 59 (3): 2625-2635
Abstract
Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ℓ1 and ℓ2 norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ℓ1-regularized QSM versus FDRI and ℓ2-regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths.
View details for DOI 10.1016/j.neuroimage.2011.08.077
View details for Web of Science ID 000299494000062
View details for PubMedID 21925274
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Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men.
Biological psychiatry
2012; 71 (3): 269-278
Abstract
Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity.We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict.Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity.Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment.
View details for DOI 10.1016/j.biopsych.2011.10.022
View details for PubMedID 22137506
View details for PubMedCentralID PMC3253929
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The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization.
Frontiers in neuroinformatics
2012; 6: 27-?
Abstract
The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T(1)-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/).
View details for DOI 10.3389/fninf.2012.00027
View details for PubMedID 23230398
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WHITE MATTER FRACTIONAL ANISOTROPY PREDICTS EVOKED DELTA AMPLITUDE DIFFERENCES IN NORMAL AGING
26th Annual Meeting of the Association-of-Professional-Sleep-Societies (APSS)
AMER ACAD SLEEP MEDICINE. 2012: A407–A407
View details for Web of Science ID 000312996502450
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The INIA19 template and NeuroMaps atlas for primate brain image parcellation and spatial normalization
FRONTIERS IN NEUROINFORMATICS
2012; 6
View details for DOI 10.3389/fninf.2012.00027
View details for Web of Science ID 000209207100027
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Age-related reorganization of functional networks for successful conflict resolution: a combined functional and structural MRI study.
Neurobiology of aging
2011; 32 (11): 2075-2090
Abstract
Aging has readily observable effects on the ability to resolve conflict between competing stimulus attributes that are likely related to selective structural and functional brain changes. To identify age-related differences in neural circuits subserving conflict processing, we combined structural and functional MRI and a Stroop Match-to-Sample task involving perceptual cueing and repetition to modulate resources in healthy young and older adults. In our Stroop Match-to-Sample task, older adults handled conflict by activating a frontoparietal attention system more than young adults and engaged a visuomotor network more than young adults when processing repetitive conflict and when processing conflict following valid perceptual cueing. By contrast, young adults activated frontal regions more than older adults when processing conflict with perceptual cueing. These differential activation patterns were not correlated with regional gray matter volume despite smaller volumes in older than young adults. Given comparable performance in speed and accuracy of responding between both groups, these data suggest that successful aging is associated with functional reorganization of neural systems to accommodate functionally increasing task demands on perceptual and attentional operations.
View details for DOI 10.1016/j.neurobiolaging.2009.12.002
View details for PubMedID 20022675
View details for PubMedCentralID PMC2888896
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Age-related reorganization of functional networks for successful conflict resolution: A combined functional and structural MRI study
NEUROBIOLOGY OF AGING
2011; 32 (11): 2075-2090
View details for DOI 10.1016/j.neurobiolaging.2009.12.002
View details for Web of Science ID 000295220700015
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Disruption of Functional Connectivity of the Default-Mode Network in Alcoholism
CEREBRAL CORTEX
2011; 21 (10): 2272-2281
Abstract
The default mode network (DMN) comprises brain structures maximally active at rest. Disturbance of network nodes or their connections occurs with some neuropsychiatric conditions and may underlie associated dysfunction. DMN connectivity has not been examined in alcoholism, which is marked by compromised DMN nodes and impaired spatial working memory. To test whether performance would be related to DMN integrity, we examined DMN functional connectivity using functional magnetic resonance imaging (fMRI) data and graph theory analysis. We assumed that disruption of short paths between network nodes would attenuate processing efficiency. Alcoholics and controls were scanned at rest and during a spatial working memory task. At rest, the spontaneous slow fluctuations of fMRI signals in the posterior cingulate and cerebellar regions in alcoholics were less synchronized than in controls, indicative of compromised functional connectivity. Graph theory analysis indicated that during rest, alcoholics had significantly lower efficiency indices than controls between the posterior cingulate seed and multiple cerebellar sites. Greater efficiency in several connections correlated with longer sobriety in alcoholics. During the task, on which alcoholics performed on par with controls, connectivity between the left posterior cingulate seed and left cerebellar regions was more robust in alcoholics than controls and suggests compensatory networking to achieve normal performance.
View details for DOI 10.1093/cercor/bhq297
View details for Web of Science ID 000294808800007
View details for PubMedID 21368086
View details for PubMedCentralID PMC3169657
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Quantification of in vivo metabolic kinetics of hyperpolarized pyruvate in rat kidneys using dynamic C-13 MRSI
NMR IN BIOMEDICINE
2011; 24 (8): 997-1005
Abstract
With signal-to-noise ratio enhancements on the order of 10,000-fold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products in vivo. Although hyperpolarized [1-(13)C]pyruvate, in particular, has been used to demonstrate metabolic activities in various animal models, robust quantification and metabolic modeling remain important areas of investigation. Enzyme saturation effects are routinely seen with commonly used doses of hyperpolarized [1-(13)C]pyruvate; however, most metrics proposed to date, including metabolite ratios, time-to-peak of metabolic products and single exchange rate constants, fail to capture these saturation effects. In addition, the widely used small-flip-angle excitation approach does not correctly model the inflow of fresh downstream metabolites generated proximal to the target slice, which is often a significant factor in vivo. In this work, we developed an efficient quantification framework employing a spiral-based dynamic spectroscopic imaging approach. The approach overcomes the aforementioned limitations and demonstrates that the in vivo (13)C labeling of lactate and alanine after a bolus injection of [1-(13)C]pyruvate is well approximated by saturatable kinetics, which can be mathematically modeled using a Michaelis-Menten-like formulation, with the resulting estimated apparent maximal reaction velocity V(max) and apparent Michaelis constant K(M) being unbiased with respect to critical experimental parameters, including the substrate dose, bolus shape and duration. Although the proposed saturatable model has a similar mathematical formulation to the original Michaelis-Menten kinetics, it is conceptually different. In this study, we focus on the (13)C labeling of lactate and alanine and do not differentiate the labeling mechanism (net flux or isotopic exchange) or the respective contribution of various factors (organ perfusion rate, substrate transport kinetics, enzyme activities and the size of the unlabeled lactate and alanine pools) to the labeling process.
View details for DOI 10.1002/nbm.1719
View details for Web of Science ID 000295293900009
View details for PubMedID 21538639
View details for PubMedCentralID PMC3169748
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Ethanol-induced changes in the expression of proteins related to neurotransmission and metabolism in different regions of the rat brain
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
2011; 99 (3): 428-436
Abstract
Despite extensive description of the damaging effects of chronic alcohol exposure on brain structure, mechanistic explanations for the observed changes are just emerging. To investigate regional brain changes in protein expression levels following chronic ethanol treatment, one rat per sibling pair of male Wistar rats was exposed to intermittent (14 h/day) vaporized ethanol, the other to air for 26 weeks. At the end of 24 weeks of vapor exposure, the ethanol group had blood ethanol levels averaging 450 mg%, had not experienced a protracted (> 16 h) withdrawal from ethanol, and revealed only mild evidence of hepatic steatosis. Extracted brains were micro-dissected to isolate the prefrontal cortex (PFC), dorsal striatum (STR), corpus callosum genu (CCg), CC body (CCb), anterior vermis (AV), and anterior dorsal lateral cerebellum (ADLC) for protein analysis with two-dimensional gel electrophoresis. Expression levels for 54 protein spots were significantly different between the ethanol- and air-treated groups. Of these 54 proteins, tandem mass spectroscopy successfully identified 39 unique proteins, the levels of which were modified by ethanol treatment: 13 in the PFC, 7 in the STR, 2 in the CCg, 7 in the CCb, 7 in the AV, and 5 in the ADLC. The functions of the proteins altered by chronic ethanol exposure were predominantly associated with neurotransmitter systems in the PFC and cell metabolism in the STR. Stress response proteins were elevated only in the PFC, AV, and ADLC perhaps supporting a role for frontocerebellar circuitry disruption in alcoholism. Of the remaining proteins, some had functions associated with cytoskeletal physiology (e.g., in the CCb) and others with transcription/translation (e.g., in the ADLC). Considered collectively, all but 4 of the 39 proteins identified in the present study have been previously identified in ethanol gene- and/or protein-expression studies lending support for their role in ethanol-related brain alterations.
View details for DOI 10.1016/j.pbb.2011.03.002
View details for Web of Science ID 000293371100020
View details for PubMedID 21397625
View details for PubMedCentralID PMC3129429
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MULTI-MODALITY IMAGING ASSESSMENT OF ALCOHOLISM'S DAMAGING EFFECT ON BRAIN SYSTEMS AND CIRCUITRY
OXFORD UNIV PRESS. 2011: 14–14
View details for Web of Science ID 000294066600059
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Developmental change in regional brain structure over 7 months in early adolescence: Comparison of approaches for longitudinal atlas-based parcellation
NEUROIMAGE
2011; 57 (1): 214-224
Abstract
Early adolescence is a time of rapid change in neuroanatomy and sexual development. Precision in tracking changes in brain morphology with structural MRI requires image segmentation with minimal error. Here, we compared two approaches to achieve segmentation by image registration with an atlas to quantify regional brain structural development over a 7-month interval in normal, early adolescent boys and girls. Adolescents were scanned twice (average interval=7.3 months), yielding adequate data for analysis in 16 boys (baseline age 10.9 to 13.9 years; Tanner Stage=1 to 4) and 12 girls (baseline age=11.2 to 13.7 years; Tanner Stage=3 to 4). Brain volumes were derived from T1-weighted (SPGR) images and dual-echo Fast Spin-Echo (FSE) images collected on a GE 3T scanner with an 8-channel phased-array head coil and analyzed by registration-based parcellation using the SRI24 atlas. The "independent" method required two inter-subject registrations: both baseline (MRI 1) to atlas and follow-up (MRI 2) to the atlas. The "sequential" method required one inter-subject registration, which was MRI 1 to the atlas, and one intra-subject registration, which was MRI 2 to MRI 1. Gray matter/white matter/CSF were segmented in both MRI-1 and MRI-2 using FSL FAST with tissue priors also based on the SRI24 atlas. Gray matter volumes were derived for 10 cortical regions, gray+white matter volumes for 5 subcortical structures, and CSF volumes for 4 ventricular regions and the cortical sulci. Across the 15 tissue regions, the coefficient of variation (CV) of change scores across individuals was significantly lower for the sequential method (CV=3.02), requiring only one inter-subject registration, than for the independent method (CV=9.43), requiring two inter-subject registrations. Volume change based on the sequential method revealed that total supratentorial and CSF volumes increased, while cortical gray matter volumes declined significantly (p<0.01) in anterior (lateral and medial frontal, anterior cingulate, precuneus, and parietal) but not posterior (occipital, calcarine) cortical regions. These volume changes occurred in all boys and girls who advanced a step in Tanner staging. Subcortical structures did not show consistent changes. Thus, longitudinal MRI assessment using robust registration methods is sufficiently sensitive to identify significant regional brain changes over a 7-month interval in boys and girls in early adolescence. Increasing the temporal resolution of the retest interval in longitudinal developmental studies could increase accuracy in timing of peak growth of regional brain tissue and refine our understanding of the neural mechanisms underlying the dynamic changes in brain structure throughout adolescence.
View details for DOI 10.1016/j.neuroimage.2011.04.003
View details for Web of Science ID 000291624100025
View details for PubMedID 21511039
View details for PubMedCentralID PMC3101309
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In vivo MRSI of hyperpolarized [1-C-13]pyruvate metabolism in rat hepatocellular carcinoma
NMR IN BIOMEDICINE
2011; 24 (5): 506-513
Abstract
Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than 1 year following diagnosis. Most patients with HCC are diagnosed at an advanced stage, and no efficient marker exists for the prediction of prognosis and/or response(s) to therapy. We have reported previously a high level of [1-(13)C]alanine in an orthotopic HCC using single-voxel hyperpolarized [1-(13)C]pyruvate MRS. In the present study, we implemented a three-dimensional MRSI sequence to investigate this potential hallmark of cellular metabolism in rat livers bearing HCC (n = 7 buffalo rats). In addition, quantitative real-time polymerase chain reaction was used to determine the mRNA levels of lactate dehydrogenase A, nicotinamide adenine (phosphate) dinucleotide dehydrogenase quinone 1 and alanine transaminase. The enzyme levels were significantly higher in tumor than in normal liver tissues within each rat, and were associated with the in vivo MRSI signal of [1-(13)C]alanine and [1-(13)C]lactate after a bolus intravenous injection of [1-(13)C]pyruvate. Histopathological analysis of these tumors confirmed the successful growth of HCC as a nodule in buffalo rat livers, revealing malignancy and hypervascular architecture. More importantly, the results demonstrated that the metabolic fate of [1-(13)C]pyruvate conversion to [1-(13)C]alanine significantly superseded that of [1-(13)C]pyruvate conversion to [1-(13)C]lactate, potentially serving as a marker of HCC tumors.
View details for DOI 10.1002/nbm.1616
View details for Web of Science ID 000291597200009
View details for PubMedID 21674652
View details for PubMedCentralID PMC3073155
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A COMPARISON OF IN VIVO NEUROCHEMICAL SEQUELAE OF BINGE ALCOHOL EXPOSURE IN WILD-TYPE WISTAR, ALCOHOL PREFERRING, AND ALCOHOL NONPREFERRING RATS
34th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2011: 206A–206A
View details for Web of Science ID 000290804301276
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UTILITY OF A BRIEF INSTRUMENT FOR ASSESSING ALCOHOL TOLERANCE IN SOCIAL DRINKERS
34th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2011: 75A–75A
View details for Web of Science ID 000290804300261
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FUNCTIONAL AND STRUCTURAL CONNECTIVITY AND EXECUTIVE CONTROL IN CHRONIC ALCOHOLISM: A COMBINED DTI AND fMRI STUDY
34th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2011: 283A–283A
View details for Web of Science ID 000290804301583
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FUNCTIONAL AND ANATOMICAL REMAPPING OF CORTICOCEREBELLAR LOOPS IN ALCOHOLISM
34th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2011: 127A–127A
View details for Web of Science ID 000290804300468
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HOW MODULATION OF FUNCTIONAL CONNECTIVITY BETWEEN LIMBIC AND FRONTOCEREBELLAR CIRCUITS FROM REST TO TASK ENABLES ALCOHOLICS TO RECOGNIZE WHO IS WHO
34th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2011: 130A–130A
View details for Web of Science ID 000290804300479
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Independent Contributions of Cortical Gray Matter, Aging, Sex and Alcoholism to K-Complex Amplitude Evoked During Sleep
SLEEP
2011; 34 (6): 787-795
Abstract
The amplitude of the N550 component derived from the averaged evoked K-complex decreases with normal aging and with alcoholism. The study was designed to determine whether these declines are related to the extent of cortical or subcortical shrinkage.Research sleep laboratory and MR imaging facility26 abstinent long-term alcoholic men, 14 abstinent long-term alcoholic women, 18 control men, and 22 control women.MRI data collected at 3T were analyzed from alcoholic and control men and women previously reported to have significantly different evoked delta activity during sleep. Segmented and parcellated MRI data collected at 3T were compared between these groups and evaluated for correlation with evoked K-complex amplitude measured at FP1, Fz, FCz, Cz, CPz, and Pz. Cortical gray matter and regional subcortical tissue volumes entered as predictors into stepwise multiple regression identified cortical gray matter as a unique significant predictor of evoked K-complex at all sites. Age added independent variance at 5 of the 6 sites, while alcoholism and sex added independent variance at frontal sites only.These data support recent intracranial studies showing cortical generation of K-complexes by indicating that cortical, but not subcortical volume contributes to K-complex amplitude. Establishing the extent of the relation between cortical volume and K-complex amplitude provides a mechanistic understanding of sleep compromise clinically relevant to normal aging, alcoholism, and likely other conditions affecting cortical volume and integrity.
View details for DOI 10.5665/SLEEP.1050
View details for Web of Science ID 000291158000015
View details for PubMedID 21629367
View details for PubMedCentralID PMC3099499
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Disruption of Emotion and Conflict Processing in HIV Infection with and without Alcoholism Comorbidity
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
2011; 17 (3): 537-550
View details for DOI 10.1017/S1355617711000348
View details for Web of Science ID 000290103600016
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Dynamic and High-Resolution Metabolic Imaging of Hyperpolarized [1-C-13]-Pyruvate in the Rat Brain Using a High-Performance Gradient Insert
MAGNETIC RESONANCE IN MEDICINE
2011; 65 (5): 1228-1233
Abstract
Fast chemical shift imaging (CSI) techniques are advantageous in metabolic imaging of hyperpolarized compounds due to the limited duration of the signal amplification. At the same time, reducing the acquisition time in hyperpolarized imaging does not necessarily lead to the conventional penalty in signal-to-noise ratio that occurs in imaging at thermal equilibrium polarization levels. Here a high-performance gradient insert was used in combination with undersampled spiral CSI to increase either the imaging speed or the spatial resolution of hyperpolarized (13)C metabolic imaging on a clinical 3T MR scanner. Both a single-shot sequence with a total acquisition time of 125 ms and a three-shot sequence with a nominal in-plane resolution of 1.5 mm were implemented. The k-space trajectories were measured and then used during image reconstruction. The technique was applied to metabolic imaging of the rat brain in vivo after the injection of hyperpolarized [1-(13)C]-pyruvate. Dynamic imaging afforded the measurement of region-of-interest-specific time courses of pyruvate and its metabolic products, while imaging at high spatial resolution was used to better characterize the spatial distribution of the metabolite signals.
View details for DOI 10.1002/mrm.22707
View details for Web of Science ID 000289760800003
View details for PubMedID 21500253
View details for PubMedCentralID PMC3126907
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Alcohol exposure and nutritional deficiency in rat models: translational neuroimaging studies
Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies
ELSEVIER SCIENCE INC. 2011: 282–82
View details for Web of Science ID 000289538300071
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Application of double spin echo spiral chemical shift imaging to rapid metabolic mapping of hyperpolarized [1-C-13]-pyruvate
JOURNAL OF MAGNETIC RESONANCE
2011; 209 (2): 332-336
Abstract
Undersampled spiral CSI (spCSI) using a free induction decay (FID) acquisition allows sub-second metabolic imaging of hyperpolarized ¹³C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence by incorporating double spin echo radiofrequency (RF) pulses to eliminate the need for phase correction and obtain high quality spectra in magnitude mode. The sequence also provides an added benefit of attenuating signal from flowing spins, which can otherwise contaminate signal in the organ of interest. The refocusing pulses can potentially lead to a loss of hyperpolarized magnetization in dynamic imaging due to flow of spins through the fringe field of the RF coil, where the refocusing pulses fail to provide complete refocusing. Care must be taken for dynamic imaging to ensure that the spins remain within the B₁-homogeneous sensitive volume of the RF coil.
View details for DOI 10.1016/j.jmr.2011.01.010
View details for Web of Science ID 000289270900030
View details for PubMedID 21316280
View details for PubMedCentralID PMC3072043
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Pontocerebellar contribution to postural instability and psychomotor slowing in HIV infection without dementia
BRAIN IMAGING AND BEHAVIOR
2011; 5 (1): 12-24
Abstract
Postural instability occurs in HIV infection, but quantitative balance tests in conjunction with neuroimaging are lacking. We examined whether infratentorial brain tissue volume would be deficient in nondemented HIV-infected individuals and whether selective tissue deficits would be related to postural stability and psychomotor speed performance. The 123 participants included 28 men and 12 women with HIV infection without dementia or alcohol use disorders, and 40 men and 43 women without medical or psychiatric conditions. Participants completed quantitative balance testing, Digit Symbol test, and a test of finger movement speed and dexterity. An infratentorial brain region, supratentorial ventricular system, and corpus callosum were quantified with MRI-derived atlas-based parcellation, and together with archival DTI-derived fiber tracking of pontocerebellar and internal and external capsule fiber systems, brain measures were correlated with test performance. The tissue ratio of the infratentorium was ~3% smaller in the HIV than control group. The HIV group exhibited performance deficits in balancing on one foot, walking toe-to-heel, Digit Symbol substitution task, and time to complete all Digit Symbol grid boxes. Total infratentorial tissue ratio was a significant predictor of balance and Digit Symbol scores. Balance scores did not correlate significantly with ventricular volumes, callosal size, or internal or external capsule fiber integrity but did so with indices of pontocerebellar tract integrity. HIV-infected individuals specifically recruited to be without complications from alcohol use disorders had pontocerebellar tissue volume deficits with functional ramifications. Postural stability and psychomotor speed were impaired and attributable, at least in part, to compromised infratentorial brain systems.
View details for DOI 10.1007/s11682-010-9107-y
View details for Web of Science ID 000286464700002
View details for PubMedID 20872291
View details for PubMedCentralID PMC3292800
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Frontally mediated inhibitory processing and white matter microstructure: age and alcoholism effects
PSYCHOPHARMACOLOGY
2011; 213 (4): 669-679
Abstract
The NOGO P3 event-related potential is a sensitive marker of alcoholism, relates to EEG oscillation in the δ and θ frequency ranges, and reflects activation of an inhibitory processing network. Degradation of white matter tracts related to age or alcoholism should negatively affect the oscillatory activity within the network.This study aims to evaluate the effect of alcoholism and age on δ and θ oscillations and the relationship between these oscillations and measures of white matter microstructural integrity.Data from ten long-term alcoholics to 25 nonalcoholic controls were used to derive P3 from Fz, Cz, and Pz using a visual GO/NOGO protocol. Total power and across trial phase synchrony measures were calculated for δ and θ frequencies. DTI, 1.5 T, data formed the basis of quantitative fiber tracking in the left and right cingulate bundles and the genu and splenium of the corpus callosum. Fractional anisotropy and diffusivity (λL and λT) measures were calculated from each tract.NOGO P3 amplitude and δ power at Cz were smaller in alcoholics than controls. Lower δ total power was related to higher λT in the left and right cingulate bundles. GO P3 amplitude was lower and GO P3 latency was longer with advancing age, but none of the time-frequency analysis measures displayed significant age or diagnosis effects.The relation of δ total power at CZ with λT in the cingulate bundles provides correlational evidence for a functional role of fronto-parietal white matter tracts in inhibitory processing.
View details for DOI 10.1007/s00213-010-2073-7
View details for Web of Science ID 000287764500002
View details for PubMedID 21161189
View details for PubMedCentralID PMC3033525
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Signs of Preclinical Wernicke's Encephalopathy and Thiamine Levels as Predictors of Neuropsychological Deficits in Alcoholism without Korsakoff's Syndrome
NEUROPSYCHOPHARMACOLOGY
2011; 36 (3): 580-588
Abstract
The purpose of this study was to determine whether meeting historical criteria for unsuspected Wernicke's encephalopathy (WE), largely under-diagnosed in vivo, explains why some alcoholics have severe neuropsychological deficits, whereas others, with a similar drinking history, exhibit preserved performance. Demographic, clinical, alcohol related, and neuropsychological measures were collected in 56 abstinent alcoholics and 38 non-alcohol-dependent volunteers. Alcoholics were classified using the clinical criteria established by Caine et al (1997) and validated in their neuropathological study of alcoholic cases. Our alcoholics who met a single criterion were considered 'at risk for WE' and those with two or more criteria with 'signs of WE'. Whole blood thiamine was also measured in 22 of the comparison group and 28 alcoholics. Of the alcoholics examined, 27% met no criteria, 57% were at risk for WE, and 16% had signs of WE. Neuropsychological performance of the alcoholic subgroups was graded, with those meeting zero criteria not differing from controls, those meeting one criterion presenting mild-to-moderate deficits on some of the functional domains, and those meeting two or more criteria having the most severe deficits on each of the domains examined. Thiamine levels were selectively related to memory performance in the alcoholics. Preclinical signs of WE can be diagnosed in vivo, enabling the identification of ostensibly 'uncomplicated' alcoholics who are at risk for neuropsychological complications. The graded effects in neuropsychological performance suggest that the presence of signs of WE explains, at least partially, the heterogeneity of alcoholism-related cognitive and motor deficits.
View details for DOI 10.1038/npp.2010.189
View details for Web of Science ID 000286176700004
View details for PubMedID 20962766
View details for PubMedCentralID PMC3055684
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Remote Semantic Memory for Public Figures in HIV Infection, Alcoholism, and Their Comorbidity
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2011; 35 (2): 265-276
Abstract
Impairments in component processes of working and episodic memory mark both HIV infection and chronic alcoholism, with compounded deficits often observed in individuals comorbid for these conditions. Remote semantic memory processes, however, have only seldom been studied in these diagnostic groups. Examination of remote semantic memory could provide insight into the underlying processes associated with storage and retrieval of learned information over extended time periods while elucidating spared and impaired cognitive functions in these clinical groups.We examined component processes of remote semantic memory in HIV infection and chronic alcoholism in 4 subject groups (HIV, ALC, HIV + ALC, and age-matched healthy adults) using a modified version of the Presidents Test. Free recall, recognition, and sequencing of presidential candidates and election dates were assessed. In addition, component processes of working, episodic, and semantic memory were assessed with ancillary cognitive tests.The comorbid group (HIV + ALC) was significantly impaired on sequencing of remote semantic information compared with age-matched healthy adults. Free recall of remote semantic information was also modestly impaired in the HIV + ALC group, but normal performance for recognition of this information was observed. Few differences were observed between the single diagnosis groups (HIV, ALC) and healthy adults, although examination of the component processes underlying remote semantic memory scores elicited differences between the HIV and ALC groups. Selective remote memory processes were related to lifetime alcohol consumption in the ALC group and to viral load and depression level in the HIV group. Hepatitis C diagnosis was associated with lower remote semantic memory scores in all 3 clinical groups. Education level did not account for group differences reported.This study provides behavioral support for the existence of adverse effects associated with the comorbidity of HIV infection and chronic alcoholism on selective component processes of memory function, with untoward effects exacerbated by Hepatitis C infection. The pattern of remote semantic memory function in HIV + ALC is consistent with those observed in neurological conditions primarily affecting frontostriatal pathways and suggests that remote memory dysfunction in HIV + ALC may be a result of impaired retrieval processes rather than loss of remote semantic information per se.
View details for DOI 10.1111/j.1530-0277.2010.01342.x
View details for Web of Science ID 000286510000010
View details for PubMedID 21121935
View details for PubMedCentralID PMC3058901
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Cerebral blood flow in posterior cortical nodes of the default mode network decreases with task engagement but remains higher than in most brain regions.
Cerebral cortex
2011; 21 (1): 233-244
Abstract
Functional neuroimaging studies provide converging evidence for existence of intrinsic brain networks activated during resting states and deactivated with selective cognitive demands. Whether task-related deactivation of the default mode network signifies depressed activity relative to the remaining brain or simply lower activity relative to its resting state remains controversial. We employed 3D arterial spin labeling imaging to examine regional cerebral blood flow (CBF) during rest, a spatial working memory task, and a second rest. Change in regional CBF from rest to task showed significant normalized and absolute CBF reductions in posterior cingulate, posterior-inferior precuneus, and medial frontal lobes . A Statistical Parametric Mapping connectivity analysis, with an a priori seed in the posterior cingulate cortex, produced deactivation connectivity patterns consistent with the classic "default mode network" and activation connectivity anatomically consistent with engagement in visuospatial tasks. The large task-related CBF decrease in posterior-inferior precuneus relative to its anterior and middle portions adds evidence for the precuneus' heterogeneity. The posterior cingulate and posterior-inferior precuneus were also regions of the highest CBF at rest and during task performance. The difference in regional CBF between intrinsic (resting) and evoked (task) activity levels may represent functional readiness or reserve vulnerable to diminution by conditions affecting perfusion.
View details for DOI 10.1093/cercor/bhq090
View details for PubMedID 20484322
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Cerebral Blood Flow in Posterior Cortical Nodes of the Default Mode Network Decreases with Task Engagement but Remains Higher than in Most Brain Regions
CEREBRAL CORTEX
2011; 21 (1): 233-244
View details for DOI 10.1093/cercor/bhq090
View details for Web of Science ID 000209071100001
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Electrophysiological evidence of enhanced performance monitoring in recently abstinent alcoholic men
PSYCHOPHARMACOLOGY
2011; 213 (1): 81-91
Abstract
Chronic alcoholism is associated with mild to moderate cognitive impairment. Under certain conditions, impairment can be ameliorated by invoking compensatory processes.To identify electrophysiological mechanisms of such compensation that would be required to resolve response conflict.14 abstinent alcoholic men and 14 similarly aged control men performed a variation of the Eriksen flanker task during an electroencephalography (EEG) recording to examine whether alcoholics could achieve and maintain control-level performance and whether EEG markers could identify evidence for the action of compensatory processes in the alcoholics. Monitoring processes engaged following a response were indexed by the correct related negativity (CRN) and error related negativity (ERN), two medial-frontal negative event-related potentials.The alcoholics were able to perform at control levels on accuracy and reaction time (RT). Alcoholics generated larger ERN amplitudes following incorrect responses and larger CRNs following correct responses than controls. Both groups showed evidence of post-error slowing. Larger CRN amplitudes in the alcoholics were related to longer RTs. Also observed in the alcoholics was an association between smaller CRN amplitudes and length of sobriety, suggesting a normalization of monitoring activity with extended abstinence.To the extent that greater amplitude of these electrophysiological markers of performance monitoring indexes greater resource allocation and performance compensation, the larger amplitudes observed in the alcoholic than control group support the view that elevated performance monitoring enables abstinent alcoholics to overcome response conflict, as was evident in their control-level performance.
View details for DOI 10.1007/s00213-010-2018-1
View details for Web of Science ID 000285781800009
View details for PubMedID 20941595
View details for PubMedCentralID PMC3015191
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Sheet-like white matter fiber tracts: representation, clustering, and quantitative analysis.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
2011; 14: 191-199
Abstract
We introduce an automated and probabilistic method for subject-specific segmentation of sheet-like fiber tracts. In addition to clustering of trajectories into anatomically meaningful bundles, the method provides statistics of diffusion measures by establishing point correspondences on the estimated medial representation of each bundle. We also introduce a new approach for medial surface generation of sheet-like fiber bundles in order too initialize the proposed clustering algorithm. Applying the new method to a population study of brain aging on 24 subjects demonstrates the capabilities and strengths of the algorithm in identifying and visualizing spatial patterns of group differences.
View details for PubMedID 21995029
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Fiber tracking functionally distinct components of the internal capsule
NEUROPSYCHOLOGIA
2010; 48 (14): 4155-4163
Abstract
The internal capsule conveys information from primary and supplementary motor areas, frontopontine and thalamic peduncles to brain stem and cerebellar regions, and from thalamus to prefrontal cortex. Neurological accidents involving the internal capsule indicate differential functional correlates with its sectors. To examine the microstructural condition of this fiber system and to test functional correlates of its sectors in health and aging, 12 younger and 12 older adults were examined with diffusion tensor imaging (DTI) fiber tracking and neuropsychological tests. Greater age-related degradation was evident in the anterior than posterior limb and in the superior than inferior division of the internal capsule. The superior division age effect was especially notable in axial and radial diffusivity. Fractional anisotropy (FA) across the three (anterior, genu, posterior) fiber bundles of the inferior division accounted for 27-73% of the variance for each neuropsychological domain. Identification of a triple dissociation indicated selective correlations between anterior FA and set shifting, genu FA and motor skills, and posterior FA and fluency. Quantitative fiber tracking combined with assessment of cognitive and motor functions enabled the identification of selective brain structure-function relations in healthy adults without lesions that were previously observed only in patients with lesions of the internal capsule.
View details for DOI 10.1016/j.neuropsychologia.2010.10.023
View details for Web of Science ID 000285668200019
View details for PubMedID 20974161
View details for PubMedCentralID PMC2993875
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Measurement of Serum, Liver, and Brain Cytokine Induction, Thiamine Levels, and Hepatopathology in Rats Exposed to a 4-Day Alcohol Binge Protocol
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2010; 34 (11): 1858-1870
Abstract
In rodent and human studies, ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). One interpretation of elevated brain Cho is that it is a marker of neuroinflammation, and some evidence suggests that EtOH exposure promotes neuroinflammation. This study aimed to determine whether binge EtOH exposure (intragastric 3 g/kg 25% EtOH every 8 hours for 4 days) would induce the expression of certain cytokines in blood, liver, or brain, thereby supporting the neuroinflammation hypothesis of elevated Cho.Ten of 18 wild-type male Wistar rats (~322 g at baseline) were exposed to EtOH and attained average blood alcohol levels of ~315 mg/dl across 4 days. Blood for cytokine immunoassays was collected at baseline, after 5 doses of EtOH (binge), and immediately preceding euthanasia either 4 or 24 hours after the last dose of EtOH. Blood was additionally assayed for the levels of thiamine and liver enzymes; liver histopathology was performed postmortem; and tissue from liver and 6 brain regions was assayed for the potential induction of 7 cytokines.There were no group effects on the levels of thiamine or its phosphate derivatives, thiamine monophosphate or thiamine diphosphate. ANOVAs of liver enzyme levels indicated that only alkaline phosphatase (ALP) levels were higher in the EtOH group than in control group at binge; ALP elevations, however, are difficult to explain in the absence of changes in the levels of additional liver enzymes. Postmortem liver pathology provided evidence for minimal microvesicular lipidosis and portocentric fibrosis in the EtOH group. Group effects on the levels of the measured cytokines in the blood (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1) were not significant. Similarly, postmortem evaluation of liver cytokines did not reveal group effects. Postmortem evaluation of the 7 cytokines in 6 brain regions (anterior cerebellar vermis, cingulate cortex, frontal cortex, hippocampus, hypothalamus, striatum) also failed to identify group effects.A single 4-day bout of binge EtOH exposure alone was insufficient to induce the expression of 7 cytokines in blood, liver, or 6 brain regions of wild-type Wistar rats. Alternative interpretations for elevations in brain Cho in response to a 4-day binge EtOH treatment are therefore necessary and may include induction of cytokines not measured herein or other noninflammatory mechanisms.
View details for DOI 10.1111/j.1530-0277.2010.01274.x
View details for Web of Science ID 000283594000005
View details for PubMedID 20662804
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Callosal microstructural abnormalities in Alzheimer's disease and alcoholism: same phenotype, different mechanisms
PSYCHIATRY RESEARCH-NEUROIMAGING
2010; 184 (1): 49-56
Abstract
Magnetic resonance (MRI) and diffusion tensor imaging (DTI) data were acquired in 13 Alzheimer's disease (AD) patients, 15 elderly alcoholics, and 32 elderly controls. Midsagittal area, length, dorsoventral height, fractional anisotropy (FA), and mean diffusivity (MD) of the total corpus callosum and volume of the lateral ventricles were measured; area, FA, and MD were also determined for the callosal genu, body, and splenium. On DTI, both patient groups had lower FA and higher MD than controls in all callosal regions. On MRI, both patient groups had smaller genu than controls; additional size deficits were present in the alcoholism group's callosal body and the AD group's splenium. The callosal arch was higher in the AD but not the alcoholic group compared with controls. The two patient groups had larger ventricles than controls, and the AD group had larger ventricles than the alcoholic group. Callosal area correlated with its height, and callosal FA and MD correlated with ventricular volume in AD, whereas callosal area correlated only with FA in alcoholics. In AD, the disruption of the callosal integrity, which was associated with distorted callosal shape, was related to ventricular dilation, which has been shown in twin studies to be under a multitude of genetic, polygenetic, and environmental influences. Conversely, in alcoholism, disruption of callosal microstructural integrity was related to shrinkage of the corpus callosum itself.
View details for DOI 10.1016/j.pscychresns.2010.07.006
View details for Web of Science ID 000283406100007
View details for PubMedID 20832253
View details for PubMedCentralID PMC2949287
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Cerebral dynamics and metabolism of hyperpolarized [1-C-13]pyruvate using time-resolved MR spectroscopic imaging
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
2010; 30 (10): 1734-1741
Abstract
Dynamic hyperpolarized [1-(13)C]pyruvate metabolic imaging in the normal anesthetized rat brain is demonstrated on a clinical 3-T magnetic resonance imaging scanner. A 12-second bolus injection of hyperpolarized [1-(13)C]pyruvate is imaged at a 3-second temporal resolution. The observed dynamics are evaluated with regard to cerebral blood volume (CBV), flow, transport, and metabolic exchange with the cerebral lactate pool. A model for brain [1-(13)C]lactate, based on blood-brain transport kinetics, CBV, and the observed pyruvate dynamics is described.
View details for DOI 10.1038/jcbfm.2010.93
View details for Web of Science ID 000282382200007
View details for PubMedID 20588318
View details for PubMedCentralID PMC2975615
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White Matter Fiber Degradation Attenuates Hemispheric Asymmetry When Integrating Visuomotor Information
JOURNAL OF NEUROSCIENCE
2010; 30 (36): 12168-12178
Abstract
Degradation of white matter fibers can affect the transmission of signals in brain circuits that normally enable integration of highly lateralized visual and motor processes. Here, we used diffusion tensor imaging tractography in combination with functional magnetic resonance imaging to examine the specific contributions of interhemispheric and intrahemispheric white matter fibers to functional measures of hemispheric transfer and parallel information processing using bilateral and unilateral left and right visual field stimulation in normal and compromised systems. In healthy adults, a greater degree of bilateral processing advantage with the left (nondominant) hand correlated with higher integrity of callosal fibers connecting occipital cortices, whereas less unilateral processing advantage with the right hand correlated with higher integrity of left-hemispheric posterior cingulate fibers. In contrast, alcoholics who have compromised callosal integrity showed less bilateral processing advantage than controls when responding with the left hand and greater unilateral processing advantage when responding with the right hand. We also found degraded left posterior cingulate and posterior callosal fibers in chronic alcoholics, which is consistent with functional imaging results of less left posterior cingulate and extrastriate cortex activation in alcoholics than controls when processing bilateral compared with unilateral visual field stimulation. Together, our results demonstrated that interhemispheric and intrahemispheric white matter fiber pathways mediate visuomotor integration asymmetrically and that subtle white matter fiber degradation in alcoholism attenuated the normal pattern of hemispheric asymmetry, which may have ramifications for the efficiency of visual information processing and fast response execution.
View details for DOI 10.1523/JNEUROSCI.2160-10.2010
View details for Web of Science ID 000281768000028
View details for PubMedID 20826679
View details for PubMedCentralID PMC2952637
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DISRUPTION OF FUNCTIONAL NETWORK CONNECTIVITY IN ALCOHOLICS
World Congress on International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL PUBLISHING, INC. 2010: 131A–131A
View details for Web of Science ID 000280252600461
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HETEROGENEITY OF BRAIN DYSMORPHOLOGY IN HUMAN ALCOHOLISM: US-FRANCE COLLABORATIVE PROJECT
World Congress on International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL PUBLISHING, INC. 2010: 52A–52A
View details for Web of Science ID 000280252600155
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EPISODIC MEMORY HETEROGENEITY IN ALCOHOLISM: EVIDENCE FROM NEUROPSYCHOLOGICAL AND NEUROIMAGING STRUCTURAL AND FUNCTIONAL STUDIES
World Congress on International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL PUBLISHING, INC. 2010: 143A–143A
View details for Web of Science ID 000280252600511
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NEURAL SYSTEMS, CIRCUITRY, AND FUNCTION: EFFECTS OF ALCOHOLISM
World Congress on International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL PUBLISHING, INC. 2010: 53A–53A
View details for Web of Science ID 000280252600156
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Dual Tasking and Working Memory in Alcoholism: Relation to Frontocerebellar Circuitry
NEUROPSYCHOPHARMACOLOGY
2010; 35 (9): 1868-1878
Abstract
Controversy exists regarding the role of cerebellar systems in cognition and whether working memory compromise commonly marking alcoholism can be explained by compromise of nodes of corticocerebellar circuitry. We tested 17 alcoholics and 31 age-matched controls with dual-task, working memory paradigms. Interference tasks competed with verbal and spatial working memory tasks using low (three item) or high (six item) memory loads. Participants also underwent structural MRI to obtain volumes of nodes of the frontocerebellar system. On the verbal working memory task, both groups performed equally. On the spatial working memory with the high-load task, the alcoholic group was disproportionately more affected by the arithmetic distractor than were controls. In alcoholics, volumes of the left thalamus and left cerebellar Crus I volumes were more robust predictors of performance in the spatial working memory task with the arithmetic distractor than the left frontal superior cortex. In controls, volumes of the right middle frontal gyrus and right cerebellar Crus I were independent predictors over the left cerebellar Crus I, left thalamus, right superior parietal cortex, or left middle frontal gyrus of spatial working memory performance with tracking interference. The brain-behavior correlations suggest that alcoholics and controls relied on the integrity of certain nodes of corticocerebellar systems to perform these verbal and spatial working memory tasks, but that the specific pattern of relationships differed by group. The resulting brain structure-function patterns provide correlational support that components of this corticocerebellar system not typically related to normal performance in dual-task conditions may be available to augment otherwise dampened performance by alcoholics.
View details for DOI 10.1038/npp.2010.56
View details for Web of Science ID 000279924400005
View details for PubMedID 20410871
View details for PubMedCentralID PMC2919220
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Transcallosal White Matter Degradation Detected With Quantitative Fiber Tracking in Alcoholic Men and Women: Selective Relations to Dissociable Functions
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2010; 34 (7): 1201-1211
Abstract
Excessive alcohol consumption can adversely affect white matter fibers and disrupt transmission of neuronal signals. Here, we examined six anatomically defined transcallosal white matter fiber bundles and asked whether any bundle was specifically vulnerable to alcohol, what aspect of white matter integrity was most affected, whether women were more vulnerable than men, and whether evidence of compromise in specific bundles was associated with deficits in balance, sustained attention, associative learning, and psychomotor function, commonly affected in alcoholics.Diffusion tensor imaging quantitative fiber tracking assessed integrity of six transcallosal white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy controls (42 men, 46 women). Measures included orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, quantified separately for axial (longitudinal; lambdaL) and radial (transverse; lambdaT) diffusivity. The Digit Symbol Test and a test of ataxia were also administered.Alcoholism negatively affected callosal FA and lambdaT of all but the sensory-motor bundle. Women showed no evidence for greater vulnerability to alcohol than men. Multiple regression analyses confirmed a double dissociation: higher diffusivity in sensory-motor and parietal bundles was associated with poorer balance but not psychomotor speed, whereas higher diffusivity in prefrontal and temporal bundles was associated with slower psychomotor speed but not balance.This study revealed stronger alcohol effects for FA and radial diffusivity than axial diffusivity, suggesting myelin degradation, but no evidence for greater vulnerability to alcohol in women than men. The presence of brain-behavior relationships provides support for the role of alcoholism-related commissural white matter degradation as a substrate of cognitive and motor impairment. Identification of a double dissociation provides further support for the role of selective white matter integrity in specific domains of performance.
View details for DOI 10.1111/j.1530-0277.2010.01197.x
View details for Web of Science ID 000279122600009
View details for PubMedID 20477772
View details for PubMedCentralID PMC2910526
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Volumetric cerebral perfusion imaging in healthy adults: Regional distribution, laterality, and repeatability of pulsed continuous arterial spin labeling (PCASL)
PSYCHIATRY RESEARCH-NEUROIMAGING
2010; 182 (3): 266-273
Abstract
The regional distribution, laterality, and reliability of volumetric pulsed continuous arterial spin labeling (PCASL) measurements of cerebral blood flow (CBF) in cortical, subcortical, and cerebellar regions were determined in 10 normal volunteers studied on two occasions separated by 3 to 7 days. Regional CBF, normalized for global perfusion, was highly reliable when measured on separate days. Several regions showed significant lateral asymmetry; notably, in frontal regions CBF was greater in the right than left hemisphere, whereas left was greater than right in posterior regions. There was considerable regional variability across the brain, whereby the posterior cingulate and central and posterior precuneus cortices had the highest perfusion and the globus pallidus the lowest gray matter perfusion. The latter may be due to iron-induced T1 shortening affecting labeled spins and computed CBF signal. High CBF in the posterior cingulate and posterior and central precuneus cortices in this task-free acquisition suggests high activity in these principal nodes of the "default mode network."
View details for DOI 10.1016/j.pscychresns.2010.02.010
View details for Web of Science ID 000279521300012
View details for PubMedID 20488671
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MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain
NEUROPSYCHOLOGY REVIEW
2010; 20 (2): 209-225
Abstract
As Norman Geschwind asserted in 1965, syndromes resulting from white matter lesions could produce deficits in higher-order functions and "disconnexion" or the interruption of connection between gray matter regions could be as disruptive as trauma to those regions per se. The advent of in vivo diffusion tensor imaging, which allows quantitative characterization of white matter fiber integrity in health and disease, has served to strengthen Geschwind's proposal. Here we present an overview of the principles of diffusion tensor imaging (DTI) and its contribution to progress in our current understanding of normal and pathological brain function.
View details for DOI 10.1007/s11065-010-9129-7
View details for Web of Science ID 000278470400008
View details for PubMedID 20422451
View details for PubMedCentralID PMC2910550
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In vivo application of sub-second spiral chemical shift imaging (CSI) to hyperpolarized C-13 metabolic imaging: Comparison with phase-encoded CSI
JOURNAL OF MAGNETIC RESONANCE
2010; 204 (2): 340-345
Abstract
A fast spiral chemical shift imaging (CSI) has been developed to address the challenge of the limited acquisition window in hyperpolarized (13)C metabolic imaging. The sequence exploits the sparsity of the spectra and prior knowledge of resonance frequencies to reduce the measurement time by undersampling the data in the spectral domain. As a consequence, multiple reconstructions are necessary for any given data set as only frequency components within a selected bandwidth are reconstructed "in-focus" while components outside that band are severely blurred ("spectral tomosynthesis"). A variable-flip-angle scheme was used for optimal use of the longitudinal magnetization. The sequence was applied to sub-second metabolic imaging of the rat in vivo after injection of hyperpolarized [1-(13)C]-pyruvate on a clinical 3T MR scanner. The comparison with conventional CSI based on phase encoding showed similar signal-to-noise ratio (SNR) and spatial resolution in metabolic maps for the substrate and its metabolic products lactate, alanine, and bicarbonate, despite a 50-fold reduction in scan time for the spiral CSI acquisition. The presented results demonstrate that dramatic reductions in scan time are feasible in hyperpolarized (13)C metabolic imaging without a penalty in SNR or spatial resolution.
View details for DOI 10.1016/j.jmr.2010.03.005
View details for Web of Science ID 000278162300021
View details for PubMedID 20346717
View details for PubMedCentralID PMC2893149
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COMPENSATORY ANTERIOR FRONTAL SLOW WAVE ACTIVITY IN RECENTLY SOBER ALCOHOLIC MEN
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 196A–196A
View details for Web of Science ID 000278107200744
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BINGE ETHANOL TREATMENT IS INSUFFICIENT TO ELEVATE CYTOKINE LEVELS MEASURED IN RAT BLOOD, LIVER, AND BRAIN
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 147A–147A
View details for Web of Science ID 000278107200549
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DISRUPTION OF BOTTOM-UP PROCESSES IN ALCOHOLICS: EXAMINATION WITH VISUOPERCEPTUAL TESTING AND QUANTITATIVE FIBER TRACKING
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 165A–165A
View details for Web of Science ID 000278107200617
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REDUCED PREFRONTAL RESPONSIVENESS TO ALCOHOL STIMULI IN CHRONIC ALCOHOLISM
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 164A–164A
View details for Web of Science ID 000278107200615
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TIME-FREQUENCY ANALYSIS OF VISUAL AND AUDITORY NOGO EVENT RELATED POTENTIALS IN ALCOHOLIC WOMEN
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 29A–29A
View details for Web of Science ID 000278107200074
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DISRUPTED FRONTOCEREBELLAR NETWORKS IN ALCOHOLICS REVEALED BY RESTING STATE FUNCTIONAL CONNECTIVITY IMAGING
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 27A–27A
View details for Web of Science ID 000278107200069
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GRADED BRAIN ABNORMALITIES IN ALCOHOLICS WITH AND WITHOUT SIGNS OF WERNICKE ENCEPHALOPATHY
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 24A–24A
View details for Web of Science ID 000278107200056
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WORKING AND EPISODIC MEMORY PROCESSES IN ALCOHOLISM, HIV, AND THEIR COMORBIDITY
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 119A–119A
View details for Web of Science ID 000278107200435
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RELATIONSHIP BETWEEN GRAY MATTER VOLUME AND SLEEP-SPECIFIC DELTA EEG CHANGES IN ALCOHOLIC MEN AND WOMEN
33rd Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2010: 23A–23A
View details for Web of Science ID 000278107200051
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Brain Injury and Recovery Following Binge Ethanol: Evidence from In Vivo Magnetic Resonance Spectroscopy
BIOLOGICAL PSYCHIATRY
2010; 67 (9): 846-854
Abstract
The binge-drinking model in rodents using intragastric injections of ethanol (EtOH) for 4 days results in argyrophilic corticolimbic tissue classically interpreted as indicating irreversible neuronal degeneration. However, recent findings suggest that acquired argyrophilia can also identify injured neurons that have the potential to recover. The current in vivo magnetic resonance (MR) imaging and spectroscopy study was conducted to test the hypothesis that binge EtOH exposure would injure but not cause the death of neurons as previously ascertained postmortem.After baseline MR scanning, 11 of 19 rats received a loading dose of 5 g/kg EtOH via oral gavage, then a maximum of 3 g/kg every 8 hours for 4 days, for a total average cumulative EtOH dose of 43 +/- 1.2 g/kg and average blood alcohol levels of 258 +/- 12 mg/dL. All animals were scanned after 4 days of gavage (post-gavage scan) with EtOH (EtOH group) or dextrose (control [Con] group) and again after 7 days of abstinence from EtOH (recovery scan).Tissue shrinkage at the post-gavage scan was reflected by significantly increased lateral ventricular volume in the EtOH group compared with the Con group. At the post-gavage scan, the EtOH group had lower dorsal hippocampal N-acetylaspartate and total creatine and higher choline-containing compounds than the Con group. At the recovery scan, neither ventricular volume nor metabolite levels differentiated the groups.Rapid recovery of ventricular volume and metabolite levels with removal of the causative agent argues for transient rather than permanent effects of a single EtOH binge episode in rats.
View details for DOI 10.1016/j.biopsych.2009.10.028
View details for Web of Science ID 000277064100008
View details for PubMedID 20044076
View details for PubMedCentralID PMC2854208
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T-2 relaxation times of C-13 metabolites in a rat hepatocellular carcinoma model measured in vivo using C-13-MRS of hyperpolarized [1-C-13]pyruvate
NMR IN BIOMEDICINE
2010; 23 (4): 414-423
Abstract
A single-voxel Carr-Purcell-Meibloom-Gill sequence was developed to measure localized T(2) relaxation times of (13)C-labeled metabolites in vivo for the first time. Following hyperpolarized [1-(13)C]pyruvate injections, pyruvate and its metabolic products, alanine and lactate, were observed in the liver of five rats with hepatocellular carcinoma and five healthy control rats. The T(2) relaxation times of alanine and lactate were both significantly longer in HCC tumors than in normal livers (p < 0.002). The HCC tumors also showed significantly higher alanine signal relative to the total (13)C signal than normal livers (p < 0.006). The intra- and inter-subject variations of the alanine T(2) relaxation time were 11% and 13%, respectively. The intra- and inter-subject variations of the lactate T(2) relaxation time were 6% and 7%, respectively. The intra-subject variability of alanine to total carbon ratio was 16% and the inter-subject variability 28%. The intra-subject variability of lactate to total carbon ratio was 14% and the inter-subject variability 20%. The study results show that the signal level and relaxivity of [1-(13)C]alanine may be promising biomarkers for HCC tumors. Its diagnostic values in HCC staging and treatment monitoring are yet to be explored.
View details for DOI 10.1002/nbm.1481
View details for Web of Science ID 000277525800011
View details for PubMedID 20175135
View details for PubMedCentralID PMC2891253
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The SRI24 Multichannel Atlas of Normal Adult Human Brain Structure
HUMAN BRAIN MAPPING
2010; 31 (5): 798-819
Abstract
This article describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template-free population registration of high-resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion-related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion-weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multichannel atlas-to-subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using diffusion tensor image fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young-old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas.
View details for DOI 10.1002/hbm.20906
View details for Web of Science ID 000277498800011
View details for PubMedID 20017133
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Metabolic Imaging in the Anesthetized Rat Brain Using Hyperpolarized [1-C-13] Pyruvate and [1-C-13] Ethyl Pyruvate
MAGNETIC RESONANCE IN MEDICINE
2010; 63 (5): 1137-1143
Abstract
Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and (13)C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-(13)C]-ethyl pyruvate relative to hyperpolarized [1-(13)C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-(13)C]-ethyl pyruvate and [1-(13)C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study.
View details for DOI 10.1002/mrm.22364
View details for Web of Science ID 000277098100001
View details for PubMedID 20432284
View details for PubMedCentralID PMC2890241
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Callosal degradation in HIV-1 infection predicts hierarchical perception: A DTI study
NEUROPSYCHOLOGIA
2010; 48 (4): 1133-1143
Abstract
HIV-1 infection affects white matter circuits linking frontal, parietal, and subcortical regions that subserve visuospatial attention processes. Normal perception requires the integration of details, preferentially processed in the left hemisphere, and the global composition of an object or scene, preferentially processed in the right hemisphere. We tested whether HIV-related callosal white matter degradation contributes to disruption of selective lateralized visuospatial and attention processes. A hierarchical letter target detection paradigm was devised, where large (global) letters were composed of small (local) letters. Participants were required to identify target letters among distractors presented at global, local, both or neither level. Attention was directed to one (global or local) or both levels. Participants were 21 HIV-1 infected and 19 healthy control men and women who also underwent Diffusion Tensor Imaging (DTI). HIV-1 participants showed impaired hierarchical perception owing to abnormally enhanced global facilitation effects but no impairment in attentional control on local-global feature selection. DTI metrics revealed poorer fiber integrity of the corpus callosum in HIV-1 than controls that was more pronounced in posterior than anterior regions. Analysis revealed a double dissociation of anterior and posterior callosal compromise in HIV-1 infection: compromise in anterior but not posterior callosal fiber integrity predicted response conflict elicited by global targets, whereas compromise in posterior but not anterior callosal fiber integrity predicted response facilitation elicited by global targets. We conclude that component processes of visuospatial perception are compromised in HIV-1 infection attributable, at least in part, to degraded callosal microstructural integrity relevant for local-global feature integration.
View details for DOI 10.1016/j.neuropsychologia.2009.12.015
View details for Web of Science ID 000275933500033
View details for PubMedID 20018201
View details for PubMedCentralID PMC2828526
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Diffusion tensor imaging of deep gray matter brain structures: Effects of age and iron concentration
NEUROBIOLOGY OF AGING
2010; 31 (3): 482-493
Abstract
Diffusion tensor imaging (DTI) of the brain has become a mainstay in the study of normal aging of white matter, and only recently has attention turned to the use of DTI to examine aging effects in gray matter structures. Of the many changes in the brain that occur with advancing age is increased presence of iron, notable in selective deep gray matter structures. In vivo detection and measurement of iron deposition is possible with magnetic resonance imaging (MRI) because of iron's effect on signal intensity. In the process of a DTI study, a series of diffusion-weighted images (DWI) is collected, and while not normally considered as a major dependent variable in research studies, they are used clinically and they reveal striking conspicuity of the globus pallidus and putamen caused by signal loss in these structures, presumably due to iron accumulation with age. These iron deposits may in turn influence DTI metrics, especially of deep gray matter structures. The combined imaging modality approach has not been previously used in the study of normal aging. The present study used legacy DTI data collected in 10 younger (22-37 years) and 10 older (65-79 years) men and women at 3.0T and fast spin-echo (FSE) data collected at 1.5T and 3.0T to derive an estimate of the field-dependent relaxation rate increase (the "FDRI estimate") in the putamen, caudate nucleus, globus pallidus, thalamus, and a frontal white matter sample comparison region. The effect of age on the diffusion measures in the deep gray matter structures was distinctly different from that reported in white matter. In contrast to lower anisotropy and higher diffusivity typical in white matter of older relative to younger adults observed with DTI, both anisotropy and diffusivity were higher in the older than younger group in the caudate nucleus and putamen; the thalamus showed little effect of age on anisotropy or diffusivity. Signal intensity measured with DWI was lower in the putamen of elderly than young adults, whereas the opposite was observed for the white matter region and thalamus. As a retrospective study based on legacy data, the FDRI estimates were based on FSE sequences, which underestimated the classical FDRI index of brain iron. Nonetheless, the differential effects of age on DTI metrics in subcortical gray matter structures compared with white matter tracts appears to be related, at least in part, to local iron content, which in the elderly of the present study was prominent in the FDRI estimate of the putamen and visibly striking in the diffusion-weighted image of the basal ganglia structures.
View details for DOI 10.1016/j.neurobiolaging.2008.04.013
View details for Web of Science ID 000276759600012
View details for PubMedID 18513834
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Mechanisms of Postural Control in Alcoholic Men and Women: Biomechanical Analysis of Musculoskeletal Coordination During Quiet Standing
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2010; 34 (3): 528-537
Abstract
Excessive sway during quiet standing is a common sequela of chronic alcoholism even with prolonged sobriety. Whether alcoholic men and women who have remained abstinent from alcohol for weeks to months differ from each other in the degree of residual postural instability and biomechanical control mechanisms has not been directly tested.We used a force platform to characterize center-of-pressure biomechanical features of postural sway, with and without stabilizing conditions from touch, vision, and stance, in 34 alcoholic men, 15 alcoholic women, 22 control men, and 29 control women. Groups were matched in age (49.4 years), general intelligence, socioeconomic status, and handedness. Each alcoholic group was sober for an average of 75 days.Analysis of postural sway when using all 3 stabilizing conditions versus none revealed diagnosis and sex differences in ability to balance. Alcoholics had significantly longer sway paths, especially in the anterior-posterior direction, than controls when maintaining erect posture without balance aids. With stabilizing conditions the sway paths of all groups shortened significantly, especially those of alcoholic men, who demonstrated a 3.1-fold improvement in sway path difference between the easiest and most challenging conditions; the remaining 3 groups, each showed a approximately 2.4-fold improvement. Application of a mechanical model to partition sway paths into open-loop and closed-loop postural control systems revealed that the sway paths of the alcoholic men but not alcoholic women were characterized by greater short-term (open-loop) diffusion coefficients without aids, often associated with muscle stiffening response. With stabilizing factors, all 4 groups showed similar long-term (closed loop) postural control. Correlations between cognitive abilities and closed-loop sway indices were more robust in alcoholic men than alcoholic women.Reduction in sway and closed-loop activity during quiet standing with stabilizing factors shows some differential expression in men and women with histories of alcohol dependence. Nonetheless, enduring deficits in postural instability of both alcoholic men and alcoholic women suggest persisting liability for falling.
View details for DOI 10.1111/j.1530-0277.2009.01118.x
View details for Web of Science ID 000275142100017
View details for PubMedID 20028360
View details for PubMedCentralID PMC2858249
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Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance
NEUROBIOLOGY OF AGING
2010; 31 (3): 464-481
Abstract
The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (lambdaL), an index of axonal length or number, and transverse diffusivity (lambdaT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age's effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.
View details for DOI 10.1016/j.neurobiolaging.2008.04.007
View details for Web of Science ID 000276759600011
View details for PubMedID 18495300
View details for PubMedCentralID PMC2815144
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Pontocerebellar volume deficits and ataxia in alcoholic men and women: no evidence for "telescoping"
PSYCHOPHARMACOLOGY
2010; 208 (2): 279-290
Abstract
Brain volume shrinkage is common in treatment-seeking patients with alcohol use disorders. Whether women are more vulnerable to brain dysmorphology than men despite lower alcohol consumption levels or shorter dependency ("telescoping effect") remains controversial and has not been considered with respect to infratentorial structures or their potential contribution to ataxia.The 200 participants included 64 men and 31 women with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence and 105 controls. An infratentorial region (pons, cerebellar hemispheres, vermis (anterior, posterior, and inferior sectors), fissures, cisterns, fourth ventricle) was quantified with atlas-based parcellation. To enable comparison of men and women, regional tissue volumes were expressed as ratios of tissue in the volume. Participants also completed quantitative ataxia testing.Total infratentorial and vermian tissue ratios were significantly smaller in alcoholics than controls; alcoholic women did not show disproportionately greater volume deficits than alcoholic men. A re-analysis including alcoholic men and women matched in alcohol consumption, onset age, abstinence duration, and age revealed again that alcoholic women did not have disproportionately greater regional vermian volume deficits than alcoholic men. Alcoholic men and women were impaired in all measures of ataxia, which correlated with low infratentorial tissue ratios in men.Alcoholic men showed deficits of pontocerebellar volume ratios, yet alcoholic women did not display signs of "telescoping". Further, alcoholic men and women both showed signs of ataxia of gait and balance, related to affected pontocerebellar systems in the men but not the women, suggesting the need to consider other neural substrates for ataxia in women.
View details for DOI 10.1007/s00213-009-1729-7
View details for Web of Science ID 000273097300011
View details for PubMedID 19943036
View details for PubMedCentralID PMC2819225
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Neurocircuitry of emotion and cognition in alcoholism: contributions from white matter fiber tractography.
Dialogues in clinical neuroscience
2010; 12 (4): 554-560
Abstract
Chronic alcoholism is characterized by impaired control over emotionally motivated actions towards alcohol use. Neuropathologically, it is associated with widespread brain structural compromise marked by gray matter shrinkage, ventricular enlargement, and white matter degradation. The extent to which cortical damage itself or cortical disconnection by white matter fiber pathway disruption contribute to deficits in emotion, cognition, and behavior can be investigated with in vivo structural neuroimaging and diffusion tensor imaging (DTI)-based quantitative fiber tracking. Tractography in alcoholism has revealed abnormalities in selective white matter fiber bundles involving limbic fiber tracts (fornix and cingulum) that connect cortico-limbic-striatal nodes of emotion and reward circuits. Studies documenting brain-behavior relationships support the role of alcoholism-related white matter fiber degradation as a substrate of clinical impairment. An understanding of the role of cortico-limbic fiber degradation in emotional dysregulation in alcoholism is now emerging.
View details for PubMedID 21319499
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Alcohol's Effects on Brain and Behavior.
Alcohol research & health
2010; 33 (1): 127-143
Abstract
Over the past 40 years, rigorous examination of brain function, structure, and attending factors through multidisciplinary research has helped identify the substrates of alcohol-related damage in the brain. One main area of this research has focused on the neuropsychological sequelae of alcoholism, which has resulted in the description of a pattern of sparing and impairment that provided an essential understanding of the functional deficits as well as of spared capabilities that could be useful in recovery. These studies have elucidated the component processes of memory, problem solving, and cognitive control, as well as visuospatial, and motor processes and their interactions with cognitive control processes. Another large area of research has focused on observable brain pathology, using increasingly sophisticated imaging technologies-progressing from pneumoencephalography to computed tomography, magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI-that have enabled ever more detailed insight into brain structure and function. These advancements also have allowed analysis of the course of brain structural changes through periods of drinking, abstinence, and relapse.
View details for PubMedID 23579943
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Alcohol's Effects on Brain and Behavior
ALCOHOL RESEARCH & HEALTH
2010; 33 (1-2): 127-143
View details for Web of Science ID 000279849800012
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Physiological and Focal Cerebellar Substrates of Abnormal Postural Sway and Tremor in Alcoholic Women
BIOLOGICAL PSYCHIATRY
2010; 67 (1): 44-51
Abstract
Posturography analysis of static balance reveals marked sway and tremor in sober alcoholic men related to anterior vermis volume but can be attenuated by simple visual or tactile cues or alterations in stance. Whether alcoholic women, whose ataxia can persist with prolonged sobriety, exhibit the same physiological signature of balance instability and relation to cerebellar vermian volume as alcoholic men or can benefit from stabilizing factors is unknown.Groups comprised 15 alcohol-dependent women, alcohol-free (median 3 months) and 29 control women. Groups were matched in age, demographic features, and finger movement speed and underwent balance platform testing and magnetic resonance imaging scanning.Alcoholic women exhibited excessive sway path length (.6 SD), more dramatic in the anterior-posterior than medial-lateral direction. Truncal tremor, measured as peak sway velocity frequency, was disproportionately great in the 5 Hz to 7 Hz band of alcoholics. Control subjects and alcoholics exhibited sway and tremor reduction with visual, tactile, or stance-stabilizing conditions, which aided both groups equally well; thus, alcoholic women never achieved normal stability. Smaller anterior vermian volumes selectively correlated with longer sway path and higher 5 Hz to 7 Hz peak sway velocity.Sway and tremor abnormalities and the selective relations between greater sway and 5 Hz to 7 Hz tremor and smaller volumes of the anterior vermis had not heretofore been described in abstinent alcoholic women. Reduction in sway and tremor with stabilizing factors indicate that adaptive mechanisms involving sensorimotor integration can be invoked to compensate for vermian-related dysfunction.
View details for DOI 10.1016/j.biopsych.2009.08.008
View details for Web of Science ID 000272858600006
View details for PubMedID 19782966
View details for PubMedCentralID PMC2794976
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FOCUS ON THE BRAIN: HIV INFECTION AND ALCOHOLISM COMORBIDITY EFFECTS ON BRAIN STRUCTURE AND FUNCTION
ALCOHOL RESEARCH & HEALTH
2010; 33 (3): 247-257
View details for Web of Science ID 000282858200009
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Focus on the Brain: HIV Infection and Alcoholism.
Alcohol research & health
2010; 33 (3): 247-257
Abstract
Both HIV infection and alcohol abuse have negative effects on the brain, with some unique to each condition and others shared by both conditions. Investigators have used magnetic resonance imaging to study the size and integrity of various brain structures in participants with alcoholism, HIV infection, or both conditions and in healthy control subjects. In these studies, alcoholics exhibited enlarged, cerebrospinal fluid-filled spaces (i.e., ventricles) as well as tissue shrinkage in various brain regions (e.g., the corpus callosum and frontal cortex), whereas study participants with asymptomatic HIV infection showed few abnormalities. Those with both HIV infection and alcoholism also had these volume abnormalities, particularly if they had experienced an AIDS-defining event. Diffusion tensor imaging, which measures the integrity of white matter fibers, has identified abnormalities of constituents of these fibers in both diseases. Again, people with HIV infection plus alcoholism show the greatest abnormalities, particularly those with a history of an AIDS-defining event. Magnetic resonance spectroscopy, which assesses the levels of brain metabolites and selective neurotransmitters, has revealed different patterns of deficits in biochemical markers of brain integrity in individuals singly affected and a compounding of effects in individuals with both HIV infection and alcoholism. Finally, neuropsychological studies have revealed impairment in selective functions involving working memory, visuospatial abilities, and movement speed that are especially likely to occur in people with comorbid HIV infection and alcoholism. Thus, alcoholism is a major risk factor for development of neuropathology and its functional sequelae in HIV-infected people.
View details for PubMedID 23584066
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Longitudinal Study of Callosal Microstructure in the Normal Adult Aging Brain Using Quantitative DTI Fiber Tracking
DEVELOPMENTAL NEUROPSYCHOLOGY
2010; 35 (3): 233-256
Abstract
We present a review of neuroimaging studies of normal adult aging conducted with diffusion tensor imaging (DTI) and data from one of the first longitudinal studies using DTI to study normal aging. To date, virtually all DTI studies of normal adult aging have been cross-sectional and have identified several patterns of white matter microstructural sparing and compromise that differentiate regional effects, fiber type, and diffusivity characteristics: (1) fractional anisotropy (FA) is lower and mean diffusivity is higher in older than younger adults, (2) aging is characterized by an anterior-to-posterior gradient of greater-to-lesser compromise also seen in superior-to-inferior fiber systems, and (3) association fibers connecting cortical sites appear to be more vulnerable to aging than projection fibers. The results of this longitudinal study of the macrostructure and microstructure of the corpus callosum yielded a consistent pattern of differences between healthy, young (20s to 30s) and elderly (60s to 70s) men and women without change over 2 years. We then divided the fibers of the corpus callosum into the midsagittal strip and the lateral distal fibers in an attempt to identify the locus of the age-related differences. The results indicated that, on average, mean values of FA and longitudinal diffusivity (lambdaL) were lower in the distal than midsagittal fibers in both groups, but the age effects and the anterior-to-posterior gradients were more pronounced for the distal than midsagittal fibers and extended more posteriorly in the distal than midsagittal fibers. Despite lack of evidence for callosal aging over 2 years, ventricular enlargement occurred and was disproportionately greater in the elderly relative to the young group, being 8.2% in the elderly but only 1.2% in the young group. Thus, different brain regions can express different rates of change with aging. Our longitudinal DTI data indicate that normal aging is associated with declining FA and increasing diffusivity in both lambdaL (longitudinal diffusivity) and lambdaT (transverse diffusivity), perhaps defining the normal ontological condition rather than a pathological one, which can be marked by low FA and low diffusivity.
View details for DOI 10.1080/87565641003689556
View details for Web of Science ID 000277518100002
View details for PubMedID 20446131
View details for PubMedCentralID PMC2867078
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Contribution of Regional White Matter Integrity to Visuospatial Construction Accuracy, Organizational Strategy, and Memory for a Complex Figure in Abstinent Alcoholics
BRAIN IMAGING AND BEHAVIOR
2009; 3 (4): 379-390
View details for DOI 10.1007/s11682-009-9080-5
View details for Web of Science ID 000272173700008
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Contribution of Regional White Matter Integrity to Visuospatial Construction Accuracy, Organizational Strategy, and Memory for a Complex Figure in Abstinent Alcoholics.
Brain imaging and behavior
2009; 3 (4): 379-390
Abstract
Visuospatial construction ability as used in drawing complex figures is commonly impaired in chronic alcoholics, but memory for such information can be enhanced by use of a holistic drawing strategy during encoding. We administered the Rey-Osterrieth Complex Figure Test (ROCFT) to 41 alcoholic and 38 control men and women and assessed the contribution of diffusion tensor imaging (DTI) measures of integrity of selected white matter tracts to ROCFT copy accuracy, copy strategy, and recall accuracy. Although alcoholics copied the figure less accurately than controls, a more holistic strategy at copy was associated with better recall in both groups. Greater radial diffusivity, reflecting compromised myelin integrity, in occipital forceps and external capsule was associated with poorer copy accuracy in both groups. Lower FA, reflecting compromised fiber microstructure in the inferior cingulate bundle, which links frontal and medial temporal episodic memory systems, was associated with piecemeal copy strategy and poorer immediate recall in the alcoholics. The correlations were generally modest and should be considered exploratory. To the extent that the inferior cingulate was relatively spared in alcoholics, it may have provided an alternative pathway to the compromised frontal system for successful copy strategy and, by extension, aided recall.
View details for DOI 10.1007/s11682-009-9080-5
View details for PubMedID 20161607
View details for PubMedCentralID PMC2811340
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In vivo glutamate decline associated with kainic acid-induced status epilepticus
BRAIN RESEARCH
2009; 1300: 65-78
Abstract
Neurophysiological, biochemical, and anatomical evidence implicates glutamatergic mechanisms in epileptic seizures. Until recently, however, longitudinal characterization of in vivo glutamate dynamics was not possible. Here, we present data using in vivo magnetic resonance spectroscopy (MRS) optimized for the detection of glutamate to identify changes that evolve following kainic acid (KA)-induced status epilepticus. Wild-type male Wistar rats underwent whole-brain MR imaging and single-voxel MRS on a clinical 3 T scanner equipped with a high-strength insert gradient coil. Scanning took place before and then 3 days, 28-32 days, and 42-50 days after induction of status epilepticus. Analyses compared 5 seizure (Sz), 5 no-seizure (NoSz; received KA but did not exhibit seizures), and 6 control (Con) animals. This longitudinal study demonstrated reduced glutamate levels in vivo in the dorsal hippocampus 3 days and 1 month following status epilepticus in Sz animals compared with Con animals. Additionally, previous results were replicated: in the Sz group, computed T2 was higher in the ventral hippocampus and limbic cortex 3 days after seizure activity compared with baseline but resolved in both regions at the 1 month scan, suggesting a transient edema. Three days following seizure activity, N-acetylaspartate (NAA) declined and lactate increased in the dorsal hippocampus of the Sz group compared with the Con and NoSz group; both metabolites approached baseline levels by the third scan. Taken together, these results support the conclusion that seizure activity following KA infusion causes loss of glutamatergic neurons.
View details for DOI 10.1016/j.brainres.2009.08.060
View details for Web of Science ID 000271819200008
View details for PubMedID 19715683
View details for PubMedCentralID PMC2783661
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Double dissociation between action-driven and perception-driven conflict resolution invoking anterior versus posterior brain systems
NEUROIMAGE
2009; 48 (2): 381-390
Abstract
The ability to select and integrate relevant information in the presence of competing irrelevant information can be enhanced by advance information to direct attention and guide response selection. Attentional preparation can reduce perceptual and response conflict, yet little is known about the neural source of conflict resolution, whether it is resolved by modulating neural responses for perceptual selection to emphasize task-relevant information or for action selection to inhibit pre-potent responses to interfering information. We manipulated perceptual information that either matched or did not match the relevant color feature of an upcoming Stroop stimulus and recorded hemodynamic brain responses to these events. Longer reaction times to incongruent than congruent color-word Stroop stimuli indicated conflict; however, conflict was even greater when a color cue correctly predicted the Stroop target's color (match) than when it did not (nonmatch). A predominantly anterior network was activated for Stroop-match and a predominantly posterior network was activated for Stroop-nonmatch. Thus, when a stimulus feature did not match the expected feature, a perceptually-driven posterior attention system was engaged, whereas when interfering, automatically-processed semantic information required inhibition of pre-potent responses, an action-driven anterior control system was engaged. These findings show a double dissociation of anterior and posterior cortical systems engaging in different types of control for perceptually-driven and action-driven conflict resolution.
View details for DOI 10.1016/j.neuroimage.2009.06.058
View details for Web of Science ID 000274723900008
View details for PubMedID 19573610
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Working and Episodic Memory in HIV Infection, Alcoholism, and Their Comorbidity: Baseline and 1-Year Follow-Up Examinations
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2009; 33 (10): 1815-1824
Abstract
Selective memory deficits occur in individuals with human immunodeficiency virus (HIV) infection and those with chronic alcoholism, but the potential compounded effect of these conditions is seldom considered, despite the high prevalence of alcohol use disorders in HIV infection.Here, we examined component processes of working and episodic memory in HIV infection and chronic alcoholism (ALC) in 4 subject groups (HIV, ALC, HIV + ALC, and normal controls) at baseline and 1-year follow-up. Accuracy scores, response times, and rate of information processing were assessed with subtests of the computerized neuropsychological test battery, the MicroCog.Although individuals with either HIV infection or alcoholism generally performed at normal levels, individuals comorbid with HIV infection and alcoholism were impaired relative to controls and to the single diagnosis groups on selective memory processes. Immediate episodic memory was impaired, whereas working memory remained intact. Ability to retain information over time was not impaired in the clinical groups. Little performance change between groups was detected over 1 year. Results could not be explained by amount of alcohol consumed over a lifetime, CD4 cell count, AIDS diagnosis, or HAART medication.This study provides behavioral support for adverse synergism of HIV infection and chronic alcoholism on brain function and is consistent with neuroimaging reports of compromised hippocampal and associated memory structures related to episodic memory processes in these 2 conditions.
View details for DOI 10.1111/j.1530-0277.2009.01020.x
View details for Web of Science ID 000270068400018
View details for PubMedID 19656122
View details for PubMedCentralID PMC2832705
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Frontostriatal fiber bundle compromise in HIV infection without dementia
AIDS
2009; 23 (15): 1977-1985
Abstract
Quantitative fiber tracking derived from diffusion tensor imaging (DTI) was used to determine whether white matter association, projection, or commissural tracts are affected in nondemented individuals with HIV infection and to identify the regional distribution of sparing and impairment of fiber systems.DTI measured fractional anisotropy and diffusivity, quantified separately for longitudinal (lambdaL) diffusivity (index of axonal injury) and transverse (lambdaT) diffusivity (index of myelin injury), in 11 association and projection white matter tracts and six commissural tracts in 29 men and 13 women with HIV infection and 88 healthy, age-matched controls (42 men and 46 women).The total group of HIV-infected individuals had higher diffusivity (principally longitudinal) than controls in the posterior sectors of the corpus callosum, internal and external capsules, and superior cingulate bundles. High longitudinal diffusivity, indicative of axonal compromise, was especially prominent in posterior callosal sectors, fornix, and superior cingulate bundle in HIV with AIDS. Unmedicated patients had notably high transverse diffusivity, indicative of myelin compromise, in the occipital forceps, inferior cingulate bundle, and superior longitudinal fasciculus. Pontocerebellar projection fibers were resistant to HIV effects as were commissural fibers coursing through premotor and sensorimotor callosal sectors.This quantitative survey of brain fiber tract integrity indicates that even nondemented HIV patients can have neuroradiological evidence for damage to association and commissural tracts. These abnormalities were vulnerable to exacerbation with AIDS and possibly mitigated by HAART.
View details for DOI 10.1097/QAD.0b013e32832e77fe
View details for Web of Science ID 000270475400006
View details for PubMedID 19730350
View details for PubMedCentralID PMC2864007
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Application of Subsecond Spiral Chemical Shift Imaging to Real-Time Multislice Metabolic Imaging of the Rat In Vivo after Injection of Hyperpolarized C-13(1)-Pyruvate
MAGNETIC RESONANCE IN MEDICINE
2009; 62 (3): 557-564
Abstract
Dynamic nuclear polarization can create hyperpolarized compounds with MR signal-to-noise ratio enhancements on the order of 10,000-fold. Both exogenous and normally occurring endogenous compounds can be polarized, and their initial concentration and downstream metabolic products can be assessed using MR spectroscopy. Given the transient nature of the hyperpolarized signal enhancement, fast imaging techniques are a critical requirement for real-time metabolic imaging. We report on the development of an ultrafast, multislice, spiral chemical shift imaging sequence, with subsecond acquisition time, achieved on a clinical MR scanner. The technique was used for dynamic metabolic imaging in rats, with measurement of time-resolved spatial distributions of hyperpolarized (13)C(1)-pyruvate and metabolic products (13)C(1)-lactate and (13)C(1)-alanine, with a temporal resolution of as fast as 1 s. Metabolic imaging revealed different signal time courses in liver from kidney. These results demonstrate the feasibility of real-time, hyperpolarized metabolic imaging and highlight its potential in assessing organ-specific kinetic parameters.
View details for DOI 10.1002/mrm.22041
View details for Web of Science ID 000269404900001
View details for PubMedID 19585607
View details for PubMedCentralID PMC2782691
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MRI estimates of brain iron concentration in normal aging: Comparison of field-dependent (FDRI) and phase (SWI) methods
NEUROIMAGE
2009; 47 (2): 493-500
Abstract
Different brain structures accumulate iron at different rates throughout the adult life span. Typically, striatal and brain stem structures are higher in iron concentrations in older than younger adults, whereas cortical white matter and thalamus have lower concentrations in the elderly than young adults. Brain iron can be measured in vivo with MRI by estimating the relaxivity increase across magnetic field strengths, which yields the Field-Dependent Relaxation Rate Increase (FDRI) metric. The influence of local iron deposition on susceptibility, manifests as MR phase effects, forms the basis for another approach for iron measurement, Susceptibility-Weighted Imaging (SWI), for which imaging at only one field strength is sufficient. Here, we compared the ability of these two methods to detect and quantify brain iron in 11 young (5 men, 6 women; 21 to 29 years) and 12 elderly (6 men, 6 women; 64 to 86 years) healthy adults. FDRI was acquired at 1.5 T and 3.0 T, and SWI was acquired at 1.5 T. The results showed that both methods detected high globus pallidus iron concentration regardless of age and significantly greater iron in putamen with advancing age. The SWI measures were more sensitive when the phase signal intensities themselves were used to define regions of interest, whereas FDRI measures were robust to the method of region of interest selection. Further, FDRI measures were more highly correlated than SWI iron estimates with published postmortem values and were more sensitive than SWI to iron concentration differences across basal ganglia structures. Whereas FDRI requires more imaging time than SWI, two field strengths, and across-study image registration for iron concentration calculation, FDRI appears more specific to age-dependent accumulation of non-heme brain iron than SWI, which is affected by heme iron and non-iron source effects on phase.
View details for DOI 10.1016/j.neuroimage.2009.05.006
View details for Web of Science ID 000267756900009
View details for PubMedID 19442747
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In Vivo Measurement of Ethanol Metabolism in the Rat Liver Using Magnetic Resonance Spectroscopy of Hyperpolarized [1-C-13]Pyruvate
MAGNETIC RESONANCE IN MEDICINE
2009; 62 (2): 307-313
Abstract
[1-(13)C]pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work (13)C-MRS of hyperpolarized [1-(13)C]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-(13)C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate-to-lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-(13)C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD(+)) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date.
View details for DOI 10.1002/mrm.21998
View details for Web of Science ID 000268432400005
View details for PubMedID 19526498
View details for PubMedCentralID PMC2780439
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Relevance of Iron Deposition in Deep Gray Matter Brain Structures to Cognitive and Motor Performance in Healthy Elderly Men and Women: Exploratory Findings
BRAIN IMAGING AND BEHAVIOR
2009; 3 (2): 167-175
View details for DOI 10.1007/s11682-008-9059-7
View details for Web of Science ID 000271090600006
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HETEROGENEITY OF BRAIN DYSMORPHOLOGY IN HUMAN ALCOHOLISM: US-FRANCE COLLABORATIVE PROJECT
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 232A–232A
View details for Web of Science ID 000266335100888
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INTERFERENCE BETWEEN MODALITIES AS A MEASURE OF PROCESSING INEFFICIENCY IN ALCOHOLICS
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 254A–254A
View details for Web of Science ID 000266335100972
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GRAY MATTER RECOVERY AND ITS RELATIONSHIP TO CHANGES IN SLEEP EVOKED RESPONSES AFTER A 12 MONTH ABSTINENCE IN LONG-TERM ALCOHOLICS
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 236A–236A
View details for Web of Science ID 000266335100901
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VISUOCONSTRUCTIONAL ACCURACY, ORGANIZATIONAL STRATEGY, AND MEMORY FOR A COMPLEX FIGURE IN ABSTINENT ALCOHOLICS: RELATION TO FIBER TRACT INTEGRITY
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 230A–230A
View details for Web of Science ID 000266335100880
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IN VIVO NEUROCHEMICAL EVIDENCE FOR ALCOHOL BINGE INDUCED NEURAL COMPROMISE AND RECOVERY IN ALCOHOL-PREFERRING RATS
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 85A–85A
View details for Web of Science ID 000266335100301
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PROCESSING OF EMOTIONAL AND ALCOHOL STIMULI IN CHRONIC ALCOHOLISM
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 87A–87A
View details for Web of Science ID 000266335100307
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DISRUPTION OF EMOTION AND CONFLICT PROCESSING IN ALCOHOLICS WITH AND WITHOUT HIV INFECTION
32nd Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2009: 238A–238A
View details for Web of Science ID 000266335100912
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Relevance of Iron Deposition in Deep Gray Matter Brain Structures to Cognitive and Motor Performance in Healthy Elderly Men and Women: Exploratory Findings.
Brain imaging and behavior
2009; 3 (2): 167-175
Abstract
Iron deposition increases in normal aging, has its greatest presence in structures of the extrapyramidal system, and may contribute to functional decline. MR imaging provides a method for indexing iron deposition in brain structures because of iron's ferromagnetic properties, which interact with the MRI environment to cause signal intensity attenuation that is quantifiable by comparing images collected at 1.5 and 3.0 T. We tested functional correlates of an MR-based iron index in 10 healthy, elderly individuals previously reported to have a higher iron burden in the putamen and lower in the thalamus than young individuals. Lower scores on the Dementia Rating Scale and longer reaction times on a two-choice attention test correlated with higher iron estimates in the caudate nucleus and putamen; poorer Mini-Mental State Examination and Digit Symbol scores correlated with lower iron estimates in the thalamus. Further analyses based on multiple regression, which considered regional FDRI estimates and volume measures as predictors of performance, identified iron but not the sampled volume as the unique predictor in each case. These exploratory correlations suggest a substrate of performance degradation in aging and have implications for regional signal darkening in an array of MR-based imaging protocols.
View details for DOI 10.1007/s11682-008-9059-7
View details for PubMedID 20161183
View details for PubMedCentralID PMC2727611
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In Vivo Evidence for Alcohol-Induced Neurochemical Changes in Rat Brain Without Protracted Withdrawal, Pronounced Thiamine Deficiency, or Severe Liver Damage
NEUROPSYCHOPHARMACOLOGY
2009; 34 (6): 1427-1442
Abstract
Magnetic resonance spectroscopy (MRS) studies in human alcoholics report decreases in N-acetylaspartate (NAA) and choline-containing (Cho) compounds. Whether alterations in brain metabolite levels are attributable to alcohol per se or to physiological effects of protracted withdrawal or impaired nutritional or liver status remains unclear. Longitudinal effects of alcohol on brain metabolites measured in basal ganglia with single-voxel MRS were investigated in sibling pairs of wild-type Wistar rats, with one rat per pair exposed to escalating doses of vaporized alcohol, the other to vapor chamber air. MRS was conducted before alcohol exposure and twice during exposure. After 16 weeks of alcohol exposure, rats achieved average blood alcohol levels (BALs) of approximately 293 mg per 100 ml and had higher Cho and a trend for higher glutamine+glutamate (Glx) than controls. After 24 weeks of alcohol exposure, BALs rose to approximately 445 mg per 100 ml, and alcohol-exposed rats had higher Cho, Glx, and glutamate than controls. Thiamine and thiamine monophosphate levels were significantly lower in the alcohol than the control group but did not reach levels low enough to be considered clinically relevant. Histologically, livers of alcohol-exposed rats exhibited greater steatosis and lower glycogenosis than controls, but were not cirrhotic. This study demonstrates a specific pattern of neurobiochemical changes suggesting excessive membrane turnover or inflammation, indicated by high Cho, and alterations to glutamate homeostasis in the rat brain in response to extended vaporized alcohol exposure. Thus, we provide novel in vivo evidence for alcohol exposure as causing changes in brain chemistry in the absence of protracted withdrawal, pronounced thiamine deficiency, or severe liver damage.
View details for DOI 10.1038/npp.2008.119
View details for Web of Science ID 000265221000007
View details for PubMedID 18704091
View details for PubMedCentralID PMC2669706
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Postural sway reduction in aging men and women: Relation to brain structure, cognitive status, and stabilizing factors
NEUROBIOLOGY OF AGING
2009; 30 (5): 793-807
Abstract
Postural stability becomes compromised with advancing age, but the neural mechanisms contributing to instability have not been fully explicated. Accordingly, this quantitative physiological and MRI study of sex differences across the adult age range examined the association between components of postural control and the integrity of brain structure and function under different conditions of sensory input and stance stabilization manipulation. The groups comprised 28 healthy men (age 30-73 years) and 38 healthy women (age 34-74 years), who completed balance platform testing, cognitive assessment, and structural MRI. The results supported the hypothesis that excessive postural sway would be greater in older than younger healthy individuals when standing without sensory or stance aids, and that introduction of such aids would reduce sway in both principal directions (anterior-posterior and medial-lateral) and in both the open-loop and closed-loop components of postural control even in older individuals. Sway reduction with stance stabilization, that is, standing with feet apart, was greater in men than women, probably because older men were less stable than women when standing with their feet together. Greater sway was related to evidence for greater brain structural involutional changes, indexed as ventricular and sulcal enlargement and white matter hyperintensity burden. In women, poorer cognitive test performance related to less sway reduction with the use of sensory aids. Thus, aging men and women were shown to have diminished postural control, associated with cognitive and brain structural involution, in unstable stance conditions and with diminished sensory input.
View details for DOI 10.1016/j.neurobiolaging.2007.08.021
View details for Web of Science ID 000265018700012
View details for PubMedID 17920729
View details for PubMedCentralID PMC2684797
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Degradation of Association and Projection White Matter Systems in Alcoholism Detected with Quantitative Fiber Tracking
BIOLOGICAL PSYCHIATRY
2009; 65 (8): 680-690
Abstract
Excessive alcohol use can cause macrostructural tissue shrinkage with regional preference for frontal systems. The extent and locus of alcoholism's effect on white matter microstructure is less known.Quantitative fiber tracking derived from diffusion tensor imaging (DTI) assessed the integrity of samples of 11 major white matter bundles in 87 alcoholics (59 men, 28 women) and 88 healthy control subjects (42 men, 46 women). Fiber integrity was expressed as fractional anisotropy (FA) and apparent diffusion coefficient (ADC), quantified separately for longitudinal diffusivity (lambdaL), a putative index of axonal integrity, and transverse diffusivity (lambdaT), a putative index of myelin integrity.Alcoholism affected FA and diffusivity, particularly lambdaT, of several fiber bundles. Frontal and superior sites (frontal forceps, internal and external capsules, fornix, and superior cingulate and longitudinal fasciculi) showed greatest abnormalities in alcoholics relative to control subjects. More posterior and inferior bundles were relatively spared. Lifetime alcohol consumption correlated with regional DTI measures in alcoholic men but not women. When matched for alcohol exposure, alcoholic women showed more DTI signs of white matter degradation than alcoholic men in several fiber bundles. Among all alcoholics, poorer performance on speeded tests correlated with DTI signs of regional white matter degradation.This survey of multiple brain fiber systems revealed a differential pattern of alcoholism's effect on regional FA and diffusivity with functional consequences attributable in part to compromised fiber microstructure with prominence in signs of myelin degradation. Sex-based differences suggest that women are at enhanced risk for alcoholism-related degradation in selective white matter systems.
View details for DOI 10.1016/j.biopsych.2008.10.039
View details for Web of Science ID 000264857400007
View details for PubMedID 19103436
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Global-Local Interference is Related to Callosal Compromise in Alcoholism: A Behavior-DTI Association Study
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2009; 33 (3): 477-489
Abstract
Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global-local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism-related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes.A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age-matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure.Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits.Global-local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference-callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.
View details for DOI 10.1111/j.1530-0277.2008.00858.x
View details for Web of Science ID 000263518400011
View details for PubMedID 19120053
View details for PubMedCentralID PMC2651990
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Neuroimaging of the Wernicke-Korsakoff Syndrome
ALCOHOL AND ALCOHOLISM
2009; 44 (2): 155-165
Abstract
Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition.Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance.Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion.Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.
View details for DOI 10.1093/alcalc/agn103
View details for Web of Science ID 000263603100009
View details for PubMedID 19066199
View details for PubMedCentralID PMC2724861
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Problem solving, working memory, and motor correlates of association and commissural fiber bundles in normal aging: A quantitative fiber tracking study
NEUROIMAGE
2009; 44 (3): 1050-1062
Abstract
Normal aging is accompanied by decline in selective cognitive and motor functions. A concurrent decline in regional white matter integrity, detectable with diffusion tensor imaging (DTI), potentially contributes to waning function. DTI analysis of white matter loci indicates an anterior-to-posterior gradient distribution of declining fractional anisotropy (FA) and increasing diffusivity with age. Quantitative fiber tracking can be used to determine regional patterns of normal aging of fiber systems and test the functional ramifications of the DTI metrics. Here, we used quantitative fiber tracking to examine age effects on commissural (genu and splenium), bilateral association (cingulate, inferior longitudinal fasciculus and uncinate), and fornix fibers in 12 young and 12 elderly healthy men and women and tested functional correlates with concurrent assessment of a wide range of neuropsychological abilities. Principal component analysis of cognitive and motor tests on which the elderly achieved significantly lower scores than the young group was used for data reduction and yielded three factors: Problem Solving, Working Memory, and Motor. Age effects--lower FA or higher diffusivity--in the elderly were prominent in anterior tracts, specifically, genu, fornix, and uncinate fibers. Differential correlations between FA or diffusivity in fiber tracts and scores on Problem Solving, Working Memory, or Motor factors provide convergent validity to the biological meaningfulness of the integrity of the fibers tracked. The observed pattern of relations supports the possibility that regional degradation of white matter fiber integrity is a biological source of age-related functional compromise and may have the potential to limit accessibility to alternative neural systems to compensate for compromised function.
View details for DOI 10.1016/j.neuroimage.2008.09.046
View details for Web of Science ID 000262301500044
View details for PubMedID 18977450
View details for PubMedCentralID PMC2632960
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Subject-matched templates for spatial normalization.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
2009; 12: 224-231
Abstract
Spatial normalization of images from multiple subjects is a common problem in group comparison studies, such as voxel-based and deformation-based morphometric analyses. Use of a study-specific template for normalization may improve normalization accuracy over a study-independent standard template (Good et al., NeuroImage, 14(1):21-36, 2001). Here, we develop this approach further by introducing the concept of subject-matched templates. Rather than using a single template for the entire population, a different template is used for every subject, with the template matched to the subject in terms of age, sex, and potentially other parameters (e.g., disease). All subject-matched templates are created from a single generative regression model of atlas appearance, thus providing a priori template-to-template correspondence without registration. We demonstrate that such an approach is technically feasible and significantly improves spatial normalization accuracy over using a single template.
View details for PubMedID 20426116
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Neuroimaging in HIV Infection and Alcoholism Comorbidity: Synergistic White Matter Damage
9th International Symposium on NeuroVirology
TAYLOR & FRANCIS INC. 2009: 95–95
View details for Web of Science ID 000270278700198
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Regression Models of Atlas Appearance
21st International Conference on Information Processing in Medical Imaging
SPRINGER-VERLAG BERLIN. 2009: 151–162
View details for Web of Science ID 000270886300013
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Subject-Matched Templates for Spatial Normalization
12th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2009)
SPRINGER-VERLAG BERLIN. 2009: 224–231
View details for Web of Science ID 000273617500028
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Regression models of atlas appearance.
Information processing in medical imaging : proceedings of the ... conference
2009; 21: 151-162
Abstract
Models of object appearance based on principal components analysis provide powerful and versatile tools in computer vision and medical image analysis. A major shortcoming is that they rely entirely on the training data to extract principal modes of appearance variation and ignore underlying variables (e.g., subject age, gender). This paper introduces an appearance modeling framework based instead on generalized multi-linear regression. The training of regression appearance models is controlled by independent variables. This makes it straightforward to create model instances for specific values of these variables, which is akin to model interpolation. We demonstrate the new framework by creating an appearance model of the human brain from MR images of 36 subjects. Instances of the model created for different ages are compared with average shape atlases created from age-matched sub-populations. Relative tissue volumes vs. age in models are also compared with tissue volumes vs. subject age in the original images. In both experiments, we found excellent agreement between the regression models and the comparison data. We conclude that regression appearance models are a promising new technique for image analysis, with one potential application being the representation of a continuum of mutually consistent, age-specific atlases of the human brain.
View details for PubMedID 19694260
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Low striatal glutamate levels underlie cognitive decline in the elderly: Evidence from in vivo molecular spectroscopy
CEREBRAL CORTEX
2008; 18 (10): 2241-2250
Abstract
Glutamate (Glu), the principal excitatory neurotransmitter of prefrontal cortical efferents, potentially mediates higher order cognitive processes, and its altered availability may underlie mechanisms of age-related decline in frontally based functions. Although animal studies support a role for Glu in age-related cognitive deterioration, human studies, which require magnetic resonance spectroscopy for in vivo measurement of this neurotransmitter, have been impeded because of the similarity of Glu's spectroscopic signature to those of neighboring spectral brain metabolites. Here, we used a spectroscopic protocol, optimized for Glu detection, to examine the effect of age in 3 brain regions targeted by cortical efferents--the striatum, cerebellum, and pons--and to test whether performance on frontally based cognitive tests would be predicted by regional Glu levels. Healthy elderly men and women had lower Glu in the striatum but not pons or cerebellum than young adults. In the combined age groups, levels of striatal Glu (but no other proton metabolite also measured) correlated selectively with performance on cognitive tests showing age-related decline. The selective relations between performance and striatal Glu provide initial and novel, human in vivo support for age-related modification of Glu levels as contributing to cognitive decline in normal aging.
View details for DOI 10.1093/cercor/bhm250
View details for Web of Science ID 000259326700002
View details for PubMedID 18234683
View details for PubMedCentralID PMC2733311
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Reproducibility study of whole-brain H-1 spectroscopic imaging with automated quantification
MAGNETIC RESONANCE IN MEDICINE
2008; 60 (3): 542-547
Abstract
A reproducibility study of proton MR spectroscopic imaging ((1)H-MRSI) of the human brain was conducted to evaluate the reliability of an automated 3D in vivo spectroscopic imaging acquisition and associated quantification algorithm. A PRESS-based pulse sequence was implemented using dualband spectral-spatial RF pulses designed to fully excite the singlet resonances of choline (Cho), creatine (Cre), and N-acetyl aspartate (NAA) while simultaneously suppressing water and lipids; 1% of the water signal was left to be used as a reference signal for robust data processing, and additional lipid suppression was obtained using adiabatic inversion recovery. Spiral k-space trajectories were used for fast spectral and spatial encoding yielding high-quality spectra from 1 cc voxels throughout the brain with a 13-min acquisition time. Data were acquired with an 8-channel phased-array coil and optimal signal-to-noise ratio (SNR) for the combined signals was achieved using a weighting based on the residual water signal. Automated quantification of the spectrum of each voxel was performed using LCModel. The complete study consisted of eight healthy adult subjects to assess intersubject variations and two subjects scanned six times each to assess intrasubject variations. The results demonstrate that reproducible whole-brain (1)H-MRSI data can be robustly obtained with the proposed methods.
View details for DOI 10.1002/mrm.21713
View details for Web of Science ID 000259053900006
View details for PubMedID 18727040
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Magnetic resonance imaging of the living brain: evidence for brain degeneration among alcoholics and recovery with abstinence.
Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism
2008; 31 (4): 362-76
Abstract
Magnetic resonance imaging (MRI) provides a safe, noninvasive method to examine the brain's macrostructure, microstructure, and some aspects of how the living brain functions. MRI is capable of detecting abnormalities that can occur with alcoholism as well as changes that can occur with sobriety and relapse. The brain pathology associated with chronic excessive alcohol consumption is well documented with imaging of the living body (i.e., in vivo imaging). Consistent findings include shrinkage of the frontal cortex,1 underlying white matter, and cerebellum and expansion of the ventricles. Some of these changes are reversible with abstinence, but some appear to be enduring. Research showing correlations between brain structure and quantitative neuropsychological testing demonstrates the functional consequences of the pathology. In addition, functional imaging studies provide evidence that the brain compensates for cognitive deficits. The myriad concomitants of alcoholism, the antecedents, and the consumption patterns each may influence the observed brain changes associated with alcoholism, which tend to be more deleterious with increasing age. The multifaceted nature of alcoholism presents unique challenges and opportunities to understand the mechanisms underlying alcoholism-induced neuropathology and its recovery. Longitudinal MRI studies of animal models of alcoholism, however, can address questions about the development and course of alcohol dependence and the scope and limits of in vivo degeneration and recovery of brain structure and concomitant function that may not be readily addressed in clinical studies.
View details for PubMedID 23584010
View details for PubMedCentralID PMC3860463
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Ventricular expansion in wild-type Wistar rats after alcohol exposure by vapor chamber
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2008; 32 (8): 1459-1467
Abstract
Structural magnetic resonance imaging (MRI) reveals widespread brain damage manifest as tissue shrinkage and complementary ventriculomegaly in human alcoholism. For an animal model to parallel the human condition, high alcohol exposure should produce similar radiologically detectable neuropathology. Our previous structural MRI study demonstrated only modest brain dysmorphology of the alcohol-preferring (P) rat with average blood alcohol levels(BALs) of 125 mg/dl achieved with voluntary consumption. Here, we tested the hypothesis that wild-type Wistar rats, exposed to vaporized alcohol ensuring higher BALs than typically achieved with voluntary consumption in rodents, would model MRI findings in the brains of humans with chronic alcoholism.The longitudinal effects of vaporized alcohol exposure on the brains of 10 wild-type Wistar rats compared with 10 sibling controls were investigated with structural MRI, conducted before (MRI 1) and after (MRI 2) 16 of alcohol exposure and after an additional 8 weeks at a higher concentration of alcohol (MRI 3).Two rats in the alcohol group died prior to MRI 2. The remaining vapor-exposed rats(n = 8) achieved BALs of 293 mg/dl by MRI 2 and 445 mg/dl by MRI 3. Whereas the controls gained 17% of their body weight from MRI 1 to MRI 3, the alcohol-exposed group lost 6%.MRI, quantified with atlas-based parcellation, revealed a profile of significant ventricular expansion,after alcohol vapor exposure, in 9 contiguous slices, extending from the dorsolateral to ventrolateral ventricles. In particular, from MRI 1 to MRI 2, this ventricular volume expanded by an average of 6.5% in the controls and by 27.1% in the alcohol-exposed rats but only an additional 1.5% in controls and 2.4% in alcohol-exposed rats from MRI 2 to MRI 3. The midsagittal volume of the full anterior-to-posterior extent of the corpus callosum grew between the first 2 MRIs in both groups followed by regression in the alcohol group by MRI 3. Although group differences were statistically significant, among animals there was substantial variability of the effects of alcohol exposure on brain morphology; some animals showed profound effects, whereas others were essentially unaffected.The ventricular dilatation and callosal shrinkage produced in wild-type rats following involuntary alcohol exposure yielded a modestly successful model of neurodysmorphology phenotypes of human alcoholism. As is the case for the human condition, however, in which some individuals express greater alcoholism-related neuropathology than others, some rats maybe more susceptible than others to extreme alcohol exposure.
View details for DOI 10.1111/j.1530-0277.2008.00721.x
View details for Web of Science ID 000258331500014
View details for PubMedID 18798357
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Frontal Callosal Fiber Integrity Selectively Predicts Coordinated Psychomotor Performance in Chronic Alcoholism
BRAIN IMAGING AND BEHAVIOR
2008; 2 (2): 74-83
View details for DOI 10.1007/s11682-007-9017-9
View details for Web of Science ID 000270994000002
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Ventricular expansion after alcohol exposure by vapor chamber in Wistar rats
Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL. 2008: 326A–326A
View details for Web of Science ID 000256497201254
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Frontal callosal integrity predicts cognitive interference compromise in HIV-infected individuals comorbid for alcoholism
Joint Scientific Meeting of the Research-Society-on-Alcoholism/International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL. 2008: 176A–176A
View details for Web of Science ID 000256497200663
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Callosal Compromise Differentially Affects Conflict Processing and Attentional Allocation in Alcoholism, HIV, and Their Comorbidity
BRAIN IMAGING AND BEHAVIOR
2008; 2 (1): 27-38
View details for DOI 10.1007/s11682-007-9014-z
View details for Web of Science ID 000270993900004
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Magnetic Resonance Imaging of the Living Brain Evidence for Brain Degeneration Among Alcoholics and Recovery With Abstinence
ALCOHOL RESEARCH & HEALTH
2008; 31 (4): 362-376
View details for Web of Science ID 000265394700006
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Volume Reconstruction by Inverse Interpolation: Application to Interleaved MR Motion Correction
11th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI2008)
SPRINGER-VERLAG BERLIN. 2008: 798–806
View details for Web of Science ID 000261373700095
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Volume reconstruction by inverse interpolation: application to interleaved MR motion correction.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
2008; 11: 798-806
Abstract
We introduce in this work a novel algorithm for volume reconstruction from data acquired on an irregular grid, e.g., from multiple co-registered images. The algorithm, which is based on an inverse interpolation formalism, is superior to other methods in particular when the input images have lower spatial resolution than the reconstructed image. Local intensity bounds are enforced by an L-BFGSB optimizer, regularize the reconstruction problem, and preserve the intensity distribution of the input images. We demonstrate the usefulness of our method by applying it to retrospective motion correction in interleaved MR images.
View details for PubMedID 18979819
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The SRI24 multi-channel brain atlas: Construction and applications
Medical Imaging 2008 Conference
SPIE-INT SOC OPTICAL ENGINEERING. 2008
View details for DOI 10.1117/12.770441
View details for Web of Science ID 000256058600008
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Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure
NEUROPSYCHOPHARMACOLOGY
2007; 32 (10): 2207-2216
Abstract
The relative roles of alcohol and thiamine deficiency in causing brain damage remain controversial in alcoholics without the Wernicke-Korsakoff syndrome. Experimental control over alcohol consumption and diet are impossible in humans but can be accomplished in animal models. This experiment was designed to differentiate the separate and combined effects on the macro- and ultrastructure of the corpus callosum of thiamine deficiency and voluntary alcohol consumption. Adult male alcohol-preferring (P) rats (9 chronically alcohol-exposed and 9 water controls) received a thiamine-deficient diet for 2 weeks. There were four groups: five rats previously exposed to alcohol were treated with pyrithiamine (a thiamine phosphorylation inhibitor); five rats never exposed to alcohol were treated with pyrithiamine; four alcohol-exposed rats were treated with thiamine; and four rats never exposed to alcohol were treated with thiamine. On day 14, thiamine was restored in all 18 rats; 2 weeks later the 10 pyrithiamine-treated rats received intraperitoneal thiamine. The rats were perfused 61 days post-pyrithiamine treatment at age 598 days. Brains were dissected and weight and volumes were calculated. Sagittal sections were stained to measure white matter structures. The corpus callosum was examined using transmission electron microscopy to determine density of myelinated fibers, fiber diameter, and myelin thickness. The corpus callosum in the alcohol/pyrithiamine group was significantly thinner, had greater fiber density, higher percentage of small fibers, and myelin thinning than in the alcohol/thiamine and water/thiamine groups. Several measures showed a graded effect, where the alcohol/pyrithiamine group had greater pathology than the water/pyrithiamine group, which had greater pathology than the two thiamine-replete groups. Across all 16 rats, thinner myelin sheaths correlated with higher percentage of small fibers. Myelin thickness and axon diameter together accounted for 71% of the variance associated with percentage of small fibers. Significant abnormalities in the alcohol/pyrithiamine group and lack of abnormality in the alcohol-exposed/thiamine-replete group indicate that thiamine deficiency caused white matter damage. The graded abnormalities across the dually to singly treated animals support a compounding effect of alcohol exposure and thiamine depletion, and indicate the potential for interaction between alcohol and thiamine deficiency in human alcohol-related brain damage.
View details for DOI 10.1038/sj.npp.1301332
View details for Web of Science ID 000249506000017
View details for PubMedID 17299515
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Component cognitive and motor processes of the digit symbol test: Differential deficits in alcoholism, HIV infection, and their comorbidity
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2007; 31 (8): 1315-1324
Abstract
Alcoholism (ALC) is highly prevalent in patients with human immunodeficiency virus (HIV) infection (HIV), and those with comorbidity (ALC+HIV) may suffer compounded deficits in cognitive and motor functions affected by both conditions. Given that each disease can adversely affect motor, visuospatial, and executive functions, we used an expanded version of the Digit Symbol (DS) test to assess the separate and combined effects of ALC and HIV infection on these cognitive and motor components.Participants were 44 ALC, 43 HIV, 55 ALC+HIV, and 49 normal controls (NC). We modified DS test administration to assess sustained attention (grid completion speed), associative learning (number of boxes completed in 15-second epochs), and incidental learning (total number-symbol pairs correctly recalled) and also used ancillary tests of fine motor, visuospatial, and executive functions to assess their relationship with the different components of DS performance. All scores were corrected for age and education based on NC performance.Neither single diagnosis group-ALC nor HIV-was impaired on DS score or grid completion speed compared with the NC group, but the dual-diagnosis ALC+HIV group was impaired. Greater lifetime alcohol consumption was associated with longer grid completion time in both ALC and ALC+HIV. The HIV group demonstrated associative learning on DS but ALC+HIV and ALC did not. All groups performed similarly on incidental learning. Multiple regression analyses demonstrated that executive functions, assessed by Color Trails 2, predicted traditional DS performance in all groups. Fine Finger Movement additionally predicted traditional DS performance and grid completion speed in HIV. Visuospatial function, assessed by ability to copy the Rey-Osterrieth complex figure, did not contribute independently to DS performance in either alcohol group.Alcoholism combined with HIV infection resulted in deficits in visuospatial psychomotor function, as assessed by the DS test, although deficits were not observed in either disease condition alone. Neither alcohol group showed associative learning, and both had compromised sustained attention. Combined cognitive and motor adverse effects of alcoholism and HIV infection were manifest in psychomotor speed, sustained attention, and associative learning of visuospatial material and are testimony to the dangers of alcohol abuse even in relatively healthy patients with HIV infection.
View details for DOI 10.1111/j.1530-0277.2007.00426.x
View details for Web of Science ID 000248044300006
View details for PubMedID 17550370
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Improvement in memory and static balance with abstinence in alcoholic men and women: Selective relations with change in brain structure
PSYCHIATRY RESEARCH-NEUROIMAGING
2007; 155 (2): 91-102
Abstract
We investigated whether changes in memory or static balance in chronic alcoholics, occurring with abstinence or relapse, are associated with changes in lateral and fourth ventricular volume. Alcoholics meeting DSM-IV criteria for Alcohol Dependence (n=15) and non-alcoholic controls (n=26) were examined twice at a mean interval of 2 years with standard Wechsler Abbreviated Scale of Intelligence (WASI), Wechsler Memory Scale-Revised (WMS-R) tests, an ataxia battery, and structural MRI. At study entry, alcoholics had been abstinent on average for over 4 months and achieved lower scores than controls on WASI General IQ Index, WMS-R General Memory Index, and the ataxia battery. The 10 alcoholics who maintained sobriety at retest did not differ at study entry in socio-demographic measures, alcohol use, or WASI and WMS-R summary scores from the five relapsers. At follow-up, abstainers improved more than controls on the WMS-R General Memory Index. Ataxia tended to improve in abstainers relative to controls. Associations were observed between memory and lateral ventricular volume change and between ataxia and fourth ventricular volume change in alcoholics but not in the controls. Both memory and ataxia can improve with sustained sobriety, and brain-behavior associations suggest selective brain structural substrates for the changes observed.
View details for DOI 10.1016/j.pscychresns.2006.12.019
View details for Web of Science ID 000248061000002
View details for PubMedID 17407808
View details for PubMedCentralID PMC1949491
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Upper and lower limb motor impairments in alcoholism, HIV infection, and their comorbidity
34th Annual Meeting of the International-Neuropsychological-Society
WILEY-BLACKWELL. 2007: 1038–44
Abstract
Both HIV infection and alcoholism can impair motor abilities involving manual dexterity and postural stability. Given the high prevalence of HIV and alcoholism comorbidity, we examined whether each disease selectively disrupts different components of upper and lower limb motor control and whether these impairments are compounded by disease comorbidity.Simple and complex upper (speed and finger dexterity) and lower (static posture) limb functions were tested in 31 men with HIV infection, 27 with alcoholism, 43 comorbid for HIV infection and alcoholism, and 22 normal healthy controls to assess whether comorbid patients would demonstrate greater motor impairment relative to those with a single diagnosis.Individuals with HIV infection and those with alcoholism had impaired upper and lower limb motor function. Disease comorbidity compounded deficits in speeded finger movement. Neither Beck Depression Inventory scores, self-reported peripheral neuropathy, nor HIV medication accounted for group differences. Lower limb motor composite scores with eyes open were correlated with upper limb motor scores in the alcoholism group.Overall, the observed impairment patterns indicate the presence of upper and lower limb motor impairment in both HIV infection and alcoholism and the relevance of alcoholism in exacerbating impairment in speeded fine finger movement, when it occurs in HIV infection.
View details for DOI 10.1111/j.1530-0277.2007.00385.x
View details for Web of Science ID 000246576500015
View details for PubMedID 17403062
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Development and resolution of brain lesions caused by pyrithiamine- and dietary-induced thiamine deficiency and alcohol exposure in the alcohol-preferring rat: A longitudinal magnetic resonance imaging and spectroscopy study
NEUROPSYCHOPHARMACOLOGY
2007; 32 (5): 1159-1177
Abstract
Wernicke's encephalopathy (WE) is characterized by lesions in thalamus, hypothalamus (including mammillary nuclei), and inferior colliculi, results in serious disabilities, has an etiology of thiamine deficiency, is treatable with thiamine, and occurs most commonly with alcoholism. Despite decades of study, whether alcohol exposure exacerbates the neuropathology or retards its resolution remains controversial. To examine patterns of brain damage and recovery resulting from thiamine deprivation with and without alcohol exposure, we conducted in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3 T in alcohol-preferring (P) rats, which had voluntarily consumed large amounts of alcohol before thiamine manipulation. A total of 18 adult male P rats (nine alcohol-exposed) received a thiamine-deficient diet for 2 weeks: 10 (five alcohol-exposed) received intraperitoneal (i.p.) pyrithiamine (PT) and eight (four alcohol-exposed) received i.p. thiamine supplementation. Neurological signs developed by day 14. Rats were scanned before thiamine depletion and 18 and 35 days after thiamine repletion. Two-dimensional J-resolved MRS single-voxel spectra with water reference were collected in a voxel subtending the thalamus; metabolite quantification was corrected for voxel tissue content. MRI identified significant enlargement of dorsal ventricles and increase in signal intensities in thalamus, inferior colliculi, and mammillary nuclei of PT compared with thiamine-treated (TT) groups from MRI 1-2, followed by significant normalization from MRI 2-3 in thalamus and colliculi, but not mammillary nuclei and lateral ventricles. Voxel-by-voxel analysis revealed additional hyperintense signal clusters in the dorsal and ventral hippocampus and enlargement of the fourth ventricle. MRS showed a significant decline and then partial recovery in thalamic N-acetylaspartate, a marker of neuronal integrity, in PT compared with TT rats, with no change detected in creatine, choline, or glutamate. PT rats with prior alcohol exposure exhibited attenuated recovery in the thalamus and arrested growth of the corpus callosum; further, two of the five alcohol-exposed PT rats died prematurely. Parenchymal and ventricular changes with thiamine manipulation concur with human radiological signs of WE. The enduring macrostructural and neurochemical abnormalities involving critical nodes of Papez circuit carry liabilities for development of amnesia and incomplete recovery from other cognitive and motor functions subserved by the affected neural systems.
View details for DOI 10.1038/sj.npp.1301107
View details for Web of Science ID 000245758800016
View details for PubMedID 16723995
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Local-global interference is modulated by age, sex and anterior corpus callosum size
BRAIN RESEARCH
2007; 1142: 189-205
Abstract
To identify attentional and neural mechanisms affecting global and local feature extraction, we devised a global-local hierarchical letter paradigm to test the hypothesis that aging reduces functional cerebral lateralization through corpus callosum (CC) degradation. Participants (37 men and women, 26-79 years) performed a task requiring global, local, or global+local attention and underwent structural MRI for CC measurement. Although reaction time (RT) slowed with age, all participants had faster RTs to local than global targets. This local precedence effect together with greater interference from incongruent local information and greater response conflict from local targets each correlated with older age and smaller callosal genu (anterior) areas. These findings support the hypothesis that the CC mediates lateralized local-global processes by inhibition of task-irrelevant information under selective attention conditions. Further, with advancing age smaller genu size leads to less robust inhibition, thereby reducing cerebral lateralization and permitting interference to influence processing. Sex was an additional modifier of interference, in that callosum-interference relationships were evident in women but not in men. Regardless of age, smaller splenium (posterior) areas correlated with less response facilitation from repetition priming of global targets in men, but with greater response facilitation from repetition priming of local targets in women. Our data indicate the following dissociation: anterior callosal structure was associated with inhibitory processes (i.e., interference from incongruency and response conflict), which are vulnerable to the effects of age and sex, whereas posterior callosal structure was associated with facilitation processes from repetition priming dependent on sex and independent of age.
View details for DOI 10.1016/j.brainres.2007.01.062
View details for Web of Science ID 000245785000021
View details for PubMedID 17335783
View details for PubMedCentralID PMC1876662
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In vivo metabolite differences between the basal ganglia and cerebellum of the rat brain detected with proton MRS at 3T
PSYCHIATRY RESEARCH-NEUROIMAGING
2007; 154 (3): 267-273
Abstract
In vivo magnetic resonance spectroscopy (MRS) enables non-invasive longitudinal tracking of brain chemistry changes that can accompany aging, neurodegenerative disease, drug addiction and experimental manipulations in animals modeling such conditions. J-coupled resonances, such as glutamate, which are highly relevant to neuropsychiatric conditions are difficult to resolve on a clinical 3T MR scanner using conventional one-dimensional MRS sequences. We, therefore, implemented Constant Time PRESS (CT-PRESS) to quantify major metabolite and neurotransmitter biochemical signals, including glutamate, in two brain regions of the rat, basal ganglia and cerebellum. We acquired spectra at two distinct time points in two independent groups of six rats and analyzed metabolite levels using either creatine or water as a reference. Our results provide evidence that CT-PRESS at 3T is adequate and reliable for in vivo detection and quantification of glutamate in the rat brain and that regional differences occur in the signal intensities of the major metabolites. That the directionality of the differences depends on whether creatine or water is used as a reference for metabolite levels emphasizes the benefit to in vivo MRS of incorporating methods to establish absolute baseline metabolite concentrations.
View details for DOI 10.1016/j.pscychresns.2006.11.005
View details for Web of Science ID 000246132000008
View details for PubMedID 17346948
View details for PubMedCentralID PMC1892789
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In vivo riber tracking in the rat brain on a clinical 3T MRI system using a high strength insert gradient coil
NEUROIMAGE
2007; 35 (3): 1077-1085
Abstract
In vivo neuroimaging methods permit longitudinal quantitative examination of the dynamic course of neurodegenerative conditions in humans and animal models and enable assessment of therapeutic efforts in mitigating disease effects on brain systems. The study of conditions affecting white matter, such as multiple sclerosis, demyelinating conditions, and drug and alcohol dependence, can be accomplished with diffusion tensor imaging (DTI), a technique uniquely capable of probing the microstructural integrity of white matter fibers in the living brain. We used a 3T clinical MR scanner equipped with an insert gradient coil that yields an order of magnitude increase in performance over the whole-body hardware to acquire in vivo DTI images of rat brain. The resolution allowed for fiber tracking evaluation of fractional anisotropy (FA) and apparent diffusion coefficients in the genu and splenium of the corpus callosum. A comparison of short (46 min) and long (92 min) acquisition time DTI protocols indicated low but adequate signal-to-noise ratio (SNR=6.2) of the shorter protocol to conduct quantitative fiber tracking enhanced by multiple acquisitions. As observed in human studies, FA in the rat splenium was higher than in the genu. Advantages of this technology include the use of similar user interface, pulse sequences, and field strength for preclinical animal and clinical human research, enhancing translational capabilities. An additional benefit of scanning at lower field strength, such as 3 T, is the reduction of artifacts due to main field inhomogeneity relative to higher field animal systems.
View details for DOI 10.1016/j.neuroimage.2007.01.006
View details for Web of Science ID 000245956100009
View details for PubMedID 17331742
View details for PubMedCentralID PMC1868575
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Diffusion tensor imaging with quantitative fibre tracking in HIV infection and alcoholism comorbidity: synergistic white matter damage
BRAIN
2007; 130: 48-64
Abstract
A substantial proportion of individuals infected with human immunodeficiency virus (HIV) also abuse alcohol. Given that each condition can disrupt brain structural integrity, with a predilection for white matter, we used MR diffusion tensor imaging (DTI) and quantitative fibre tracking to examine the separate and combined effects on the microstructure of the corpus callosum. Subjects were men and women with alcoholism alone (n = 87), HIV infection alone (n = 42), alcoholism and HIV infection comorbidity (n = 52) and non-affected controls (n = 88). The two alcoholism groups had similar lifetime alcohol consumption histories; the two HIV-infected groups had similar CD4+ counts and viral loads; all groups were matched in body mass index, and no participant was demented. Compared with controls, all patient groups had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in callosal regions and fibre bundles coursing through the genu and splenium, but these effects were only significant in the two groups with alcoholism, which exhibited 0.65-1.2 SD abnormalities in FA and MD. The callosal regions were differentially affected by alcoholism, with the genu more affected than the splenium, a pattern even more pronounced in the fibre tracks. When the HIV-infected groups were divided by disease severity defined as an acquired immunodeficiency syndrome (AIDS)-defining event or low CD4+ counts (<200) and alcoholism comorbidity, the HIV-infected subgroup with AIDS and alcoholism exhibited approximately 2 SD FA and MD abnormalities in the callosal sectors and fibres, abnormalities that were more than twice the effect sizes observed in the other three HIV-infected subgroups. Degradation of the callosal microstructure was consistently associated with alcoholism, with evidence for compounded alcoholism-HIV effects. Functional relevance of the microstructural abnormalities was supported by associations between motor deficits and low FA or high MD within the diagnostic groups. The high prevalence of alcoholism in HIV-infected individuals and the interfering effect of alcohol on HIV pharmacological response and therapy compliance underscore the need to recognize the independent and synergistic contributions of each condition to brain structure and function.
View details for DOI 10.1093/brain/awl242
View details for Web of Science ID 000243061500005
View details for PubMedID 16959813
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Divergence-based framework for diffusion tensor clustering, interpolation, and regularization
20th International Conference on Information Processing in Medical Imaging
SPRINGER-VERLAG BERLIN. 2007: 507–518
View details for Web of Science ID 000247867400042
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Neuroradiological characterization of normal adult ageing
BRITISH JOURNAL OF RADIOLOGY
2007; 80: S99-S108
Abstract
This paper provides a review of MRI and diffusion tensor imaging (DTI) findings in normal ageing as an essential context for evaluating imaging in dementia, and adding to the ever-growing number of such overviews. An additional extensive literature details the physics, MR acquisition, image reconstruction and mathematical computation approaches to both imaging modalities. The aim of this review is to illustrate how MR imaging modalities, spanning structural and diffusion tensor imaging, are suitable for visualizing and quantifying the macrostructural and microstructural disruptions sustained by the brain in normal ageing and to recognize the importance of normative data for identifying abnormalities characterizing neurodegenerative diseases and other conditions affecting brain tissue integrity.
View details for DOI 10.1259/bjr/22893432
View details for Web of Science ID 000256312300005
View details for PubMedID 18445750
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Divergence-based framework for diffusion tensor clustering, interpolation, and regularization.
Information processing in medical imaging : proceedings of the ... conference
2007; 20: 507-518
Abstract
This paper introduces a novel framework for diffusion tensor combination, which can be used for tensor averaging, clustering, interpolation, and regularization. The framework is based on the physical interpretation of the tensors as the covariance matrices of Gaussian probability distributions. The symmetric Kullback-Leibler divergence provides a natural distance measure on these distributions, which leads to a closed-form expression for the distance between any two diffusion tensors, as well as for the weighted average of an arbitrary number of tensors. We illustrate the application of our technique in four different scenarios: (a) to combine tensor data from multiple subjects and generate population atlases from ten young and ten older subjects, (b) to perform k-means clustering and generate a compact Gaussian mixture of multiple tensors, (c) to interpolate between tensors, and (d) to regularize (i.e., smooth) noisy tensor data. For boundary-preserving regularization, we also propose a non-linear two-stage smoothing algorithm that can be considered remotely similar to a median filter.
View details for PubMedID 17633725
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Alcoholism, HIV infection, and their comorbidity: Factors affecting self-rated health-related quality of life
JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
2007; 68 (1): 115-125
Abstract
Both alcoholism and HIV infection reduce health-related quality of life (HRQOL), and their co-occurrence is highly prevalent. We sought to determine whether comorbidity for both disorders further reduced HRQOL and what factors exacerbated or mitigated their effect.HRQOL, CD4 T-cell counts, lifetime alcohol consumption and length of sobriety, depressive symptoms (Beck Depression Inventory [BDI]-II), general cognitive status (Peabody Picture Vocabulary Test II), and other psychiatric comorbidities were assessed in patients with alcohol dependence or abuse (n = 44), HIV infection (n = 44), alcohol + HIV (n = 55), and healthy controls (n = 41).Alcohol + HIV patients had lower HRQOL and more psychiatric comorbidities compared with patients with only HIV or those with only alcohol dependence or abuse; however, they matched HIV patients with regard to CD4 counts and matched alcohol patients on lifetime alcohol consumption. Across patient groups, higher HRQOL was associated with lower BDI scores but was not associated with age, gender, lifetime alcohol use, or viral load. HRQOL was higher for alcoholics in remission than for those currently meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. In stepwise regression, BDI total score predicted 34% of HRQOL variance in alcohol, 52% in alcohol + HIV, and 55% in HIV groups. General cognitive status contributed an additional 4% to the prediction of HRQOL but only in the alcohol + HIV group.The superimposition of HIV infection onto alcoholism has a negative impact on HRQOL independent of the severity of either disease. Depression strongly predicts HRQOL, and general cognitive status plays a small role in enhancing quality of life for those at greatest clinical disadvantage.
View details for Web of Science ID 000248712600015
View details for PubMedID 17149525
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In vivo quantification of ethanol kinetics in rat brain
NEUROPSYCHOPHARMACOLOGY
2006; 31 (12): 2683-2691
Abstract
Proton magnetic resonance spectroscopy was used at 3T to measure the uptake and clearance of brain ethanol in rats after bolus intraperitoneal (i.p.) or intragastric (i.g.) alcohol injection, and to estimate the effects of acute alcohol on brain metabolites. The observation duration was 1-1.5 h with temporal resolution of alcohol sampling ranging from 4 s-4 min. The observed time course of alcohol brain concentration followed a consistent pattern characterized by a rapid absorption, an intermediate distribution, and a slower clearance that approached a linear decay. In a sample of eight healthy Wistar rats, the intercept of the linear clearance term, extrapolated back to the time of injection, correlated well with the administered dose per unit of lean body mass. Alcohol concentration estimation based on spectroscopically measured clearance was compared with blood alcohol levels from blood samples at the end of observation, and were in good agreement with the administered dose. Serial proton spectroscopy measurements provide a valid in vivo method for quantifying brain alcohol uptake and elimination kinetics in real time.
View details for DOI 10.1038/sj.npp.1301023
View details for Web of Science ID 000242046800013
View details for PubMedID 16407891
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Relation between self-reported peripheral neuropathy and brain morphology and function in HIV infection with alcoholism comorbidity
45th Annual Meeting of the American-College-of-Neuropsychopharmacology
NATURE PUBLISHING GROUP. 2006: S80–S80
View details for Web of Science ID 000242215900231
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Callosal involvement in a lateralized Stroop task in alcoholic and healthy subjects
NEUROPSYCHOLOGY
2006; 20 (6): 727-736
Abstract
To investigate the role of interhemispheric attentional processes, 25 alcoholic and 28 control subjects were tested with a Stroop match-to-sample task and callosal areas were measured with magnetic resonance imaging. Stroop color-word stimuli were presented to the left or right visual field (VF) and were preceded by a color cue that did or did not match the word's color. For matching colors, both groups showed a right VF advantage; for nonmatching colors, controls showed a left VF advantage, whereas alcoholic subjects showed no VF advantage. For nonmatch trials, VF advantage correlated with callosal splenium area in controls but not alcoholic subjects, supporting the position that information presented to the nonpreferred hemisphere is transmitted via the splenium to the hemisphere specialized for efficient processing. The authors speculate that alcoholism-associated callosal thinning disrupts this processing route.
View details for DOI 10.1037/0894-4105.20.6.727
View details for Web of Science ID 000241761000011
View details for PubMedID 17100517
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Contribution of alcoholism to brain dysmorphology in HIV infection: Effects on the ventricles and corpus callosum
NEUROIMAGE
2006; 33 (1): 239-251
Abstract
Nonrigid registration and atlas-based parcellation methods were used to compare the volume of the ventricular system and the cross-sectional area of the midsagittal corpus callosum on brain MRIs from 272 subjects in four groups: patients with HIV infection, with and without alcoholism comorbidity, alcoholics, and controls. Prior to testing group differences in regional brain metrics, each measure was corrected by regression analysis for significant correlations with supratentorial cranial volume and age, observed in 121 normal control men and women, whose age spanned six decades. Disregarding HIV disease severity, we observed a graded pattern of modest enlargement of the total ventricular system (0.28 SD for uncomplicated HIV, 0.65 SD for HIV comorbid with alcoholism, and 0.72 SD for the alcoholism group). The pattern of callosal thinning showed a similar but small ( approximately 0.5 SD) graded effect. A different pattern emerged, however, when HIV severity in the context of alcoholism comorbidity was factored into the analysis. Substantially greater volume abnormalities were present in individuals with a history of an AIDS-defining event or low CD4+ T cell counts (
View details for DOI 10.1016/j.neuroimage.2006.05.052
View details for Web of Science ID 000241209800025
View details for PubMedID 16877010
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From rats to monkeys to man - The neurophysiology of alcoholism: A tribute to Henri Begleiter
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2006; 30 (10): 1641-1642
View details for DOI 10.1111/j.1530-0277.2006.00232.x
View details for Web of Science ID 000240818600006
View details for PubMedID 17010129
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A quantitative morphometric analysis of myelinated fibres in corpus callosum following thiamine deficiency and alcohol exposure in the alcohol-preferring (P) rat
World Congress on Alcohol Research
WILEY-BLACKWELL. 2006: 159A–159A
View details for Web of Science ID 000239919900459
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Effect of vision, touch and stance on cerebellar vermian-related sway and tremor: A quantitative physiological and MRI study
CEREBRAL CORTEX
2006; 16 (8): 1077-1086
Abstract
Postural balance is impaired in individuals with pathology of the anterior superior vermis of the cerebellum. Chronic alcoholism, with its known vermian pathology, provides a viable model for studying the relationship between cerebellar pathology and postural stability. Decades of separate study of recovering alcoholics and post-mortem neuroanatomical analysis have demonstrated vermian pathology but few studies have used quantitative posturography, acquired concurrently with quantitative neuroimaging, to establish whether this brain structure-function relationship is selective in vivo. Here, 30 healthy men and 39 chronic alcoholic men, abstinent from alcohol for several months, underwent MRI for volumetric quantitation of the cerebellar vermis and three comparison brain regions, the cerebellar hemispheres, supratentorial cortex and corpus callosum. All subjects also participated in an experiment involving a force platform that measured sway path length and tremor during static standing balance under four sensory conditions and two stance conditions. Three novel findings emerged: (i) sway path length, a physiological index of postural control, was selectively related to volume of the cerebellar vermis and not to any comparison brain region in the alcoholics; (ii) spectral analysis revealed sway prominence in the 2-5 Hz band, another physiological sign of vermian lesions and also selectively related to vermian volume in the alcoholics; and (iii) despite substantial postural sway in the patients, they successfully used vision, touch and stance to normalize sway and reduce tremor. The selective relationship of sway path to vermian but not lateral cerebellar volume provides correlational evidence for functional differentiation of these cerebellar regions. Improvement to virtual normal levels in balance and reduction in sway and tremor with changes in vision, touch and stance provide evidence that adaptive mechanisms recruiting sensorimotor integration can be invoked to compensate for underlying cerebellar vermian-related dysfunction.
View details for DOI 10.1093/cercor/bhj048
View details for Web of Science ID 000238906300003
View details for PubMedID 16221930
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Longitudinal brain magnetic resonance imaging study of the alcohol-preferring rat. Part II: Effects of voluntary chronic alcohol consumption
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2006; 30 (7): 1248-1261
Abstract
Tracking the dynamic course of human alcoholism brain pathology can be accomplished only through naturalistic study and without opportunity for experimental manipulation. Development of an animal model of alcohol-induced brain damage, in which animals consume large amounts of alcohol following cycles of alcohol access and deprivation and are examined regularly with neuroimaging methods, would enable hypothesis testing focused on the degree, nature, and factors resulting in alcohol-induced brain damage and the prospects for recovery or relapse.We report the results of longitudinal magnetic resonance imaging (MRI) studies of the effects of free-choice chronic alcohol intake on the brains of 2 cohorts of selectively bred alcohol-preferring (P) rats. In the companion paper, we described the MRI acquisition and analysis methods, delineation of brain regions, and growth patterns in total brain and selective structures of the control rats in the present study. Both cohorts were studied as adults for about 1 year and consumed high doses of alcohol for most of the study duration. The paradigm involved a 3-bottle choice with 0, 15 (or 20%), and 30% (or 40%) alcohol available in several different exposure schemes: continuous exposure, cycles of 2 weeks on followed by 2 weeks off alcohol, and binge drinking in the dark.Brain structures of the adult P rats in both the alcohol-exposed and the water control conditions showed significant growth, which was attenuated in a few measures in the alcohol-exposed groups. The region with the greatest demonstrable effect was the corpus callosum, measured on midsagittal images.The P rats showed an age-alcohol interaction different from humans, in that normal growth in selective brain regions that continues in adult rats was retarded.
View details for DOI 10.1111/j.1530-0277.2006.00146.x
View details for Web of Science ID 000238253100019
View details for PubMedID 16792573
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Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking
CEREBRAL CORTEX
2006; 16 (7): 1030-1039
Abstract
The corpus callosum, the principal white matter structure enabling interhemispheric information transfer, is heterogeneous in its microstructural composition, heterotopic in its anteroposterior cortical connectivity, and differentially susceptible to aging. In vivo characterization of callosal features is possible with diffusion tensor imaging (DTI), a magnetic resonance imaging method sensitive to the detection of white matter's linear structure. We implemented a quantitative fiber tracking approach to examine age-related variation in regional microstructural characteristics [fractional anisotropy (FA) and apparent diffusion coefficient (ADC)] of callosal fibers in 10 younger (29 +/- 5 years) and 10 older (72 +/- 5 years) healthy adults. Fiber tracking was performed on 2.5 mm isotropic voxels collected at 3 T. Fiber targets comprised the midsagittal corpus callosum, divided into six regions based on known callosal anatomical projections. FA and ADC for each voxel of each fiber identified were determined; lower FA and higher ADC reflect degraded microstructural tissue integrity. Older subjects had lower FA (P < 0.002), higher ADC (P < 0.006), and fewer (P < 0.005) fibers than younger subjects. Group x region interactions indicated disproportionately lower FA (P = 0.0001) and higher ADC (P < 0.006) in the older than younger group in frontal fiber bundles relative to posterior bundles. As a test of the functional significance of the fiber bundle metrics, the older subjects were administered the Stroop Task, which showed significant correlations between regional fiber bundle integrity and performance. These results validate this quantitative fiber tracking approach and confirm the selective vulnerability of frontal white matter systems to normal aging, likely substrates of age-related declines in cognitive processes dependent on prefrontal circuitry integrity.
View details for DOI 10.1093/cercor/bhj045
View details for Web of Science ID 000238391200012
View details for PubMedID 16207932
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Dysmorphology and microstruotural degradation of the corpus callosum: Interaction of age and alcoholism
NEUROBIOLOGY OF AGING
2006; 27 (7): 994-1009
Abstract
Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.
View details for DOI 10.1016/j.neurobiolaging.2005.05.007
View details for Web of Science ID 000238012700011
View details for PubMedID 15964101
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Longitudinal brain magnetic resonance imaging study of the alcohol-preferring rat. Part I: Adult brain growth
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2006; 30 (7): 1234-1247
Abstract
The alcohol-preferring (P) rat, a Wistar strain selectively bred to consume large amounts of alcohol voluntarily, has been used as an animal model of human alcoholism for 3 decades. Heretofore, knowledge about brain morphology has been confined to postmortem examination. Quantitative neuroimaging procedures make it feasible to examine the potential longitudinal effects of alcohol exposure in vivo, while controlling modifying factors, such as age, nutrition, and exercise. To date, few imaging studies have considered what morphological changes occur with age in the rodent brain, and none has systematically applied quantitative neuroimaging approaches to measure volume changes in regional brain structures over extended periods in the adult rat.We used structural magnetic resonance imaging (MRI) in a longitudinal design to examine 2 cohorts of adult P rats, never exposed to alcohol: Cohort A included 8 rats, 7 of which survived the entire study (578 days) and 4 MRI sessions; Cohort B included 9 rats, all of which survived the study (452 days) and 5 MRI sessions.Growth in whole-brain volume reached maximal levels by about 450 days of age, whereas body weight continued its gain without asymptote. Growth was not uniform across the brain structures measured. Over the initial 12 months of the study, the corpus callosum area expanded 36%, cerebellum 17%, and hippocampus 10%, whereas ventricle size was unchanged. Factors affecting growth rate estimates included litter effects, MR image signal-to-noise ratio, and measurement error.Unlike longitudinal human reports of regional volume declines in aging brain tissue, several brain structures in adult rats continued growing, and some growth patterns were litter-dependent. Determining normal regional growth patterns of brain and of the substantial variance exerted by litter differences, even in selectively bred rats, is essential for establishing baselines against which normal and aberrant dynamic changes can be detected in animal models of aging and disease.
View details for DOI 10.1111/j.1530-0277.2006.00145.x
View details for Web of Science ID 000238253100018
View details for PubMedID 16792572
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Effect of alcoholism and HIV comorbidity on the macrostructure and microstructure of the corpus callosum.
29th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2006: 192A–192A
View details for Web of Science ID 000238299401192
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Alcoholism and age contribute to slowed visual conjunction search
29th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2006: 155A–155A
View details for Web of Science ID 000238299401041
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Alcoholism, HIV, and their comorbidity: Factors affecting health-related quality of life
29th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2006: 91A–91A
View details for Web of Science ID 000238299400340
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Selective distribution of thiamine deficiency-induced neuronal damage and recovery in a rat model of Wernicke's encephalopathy: An MR imaging and spectroscopy study
29th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2006: 193A–193A
View details for Web of Science ID 000238299401195
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FMRI evidence for individual differences in premotor modulation of extrastriatal visual-perceptual processing of redundant targets
NEUROIMAGE
2006; 30 (3): 973-982
Abstract
To perceive the vast array of stimuli in the world around us, the visual system employs parallel processing mechanisms that ensure efficiency in perceiving multiple objects in a scene. A way to test this efficiency is to measure reaction time (RT) to pairs of identical stimuli, presented singly or as doublets; typically, the resulting phenomenon is the redundant targets effect (RTE), which manifests as faster RTs to paired than singly presented stimuli. It is controversial, however, whether the neural locus of the parallel processing mechanisms invoked to produce the RTE is perceptual or motor and why some studies observe a substantial RTE and others do not. To resolve these two issues, we measured the RTE in young adults while undergoing functional MRI. Regarding the question of a perceptual or motor basis for the RTE, we observed that bilateral activation of extrastriate cortex was prominent in paired vs. the sum of the two single stimulus conditions, indicating that the RTE invoked perceptual mechanisms; by contrast, the motor cortex was not disproportionately activated in this comparison. Regarding the magnitude of the RTE, we compared activation patterns in individuals with small vs. large RTEs and observed that frontal and premotor areas were activated with small RTEs. These data indicate that the primary processing level of response facilitation, observed as the RTE, is perceptual, but the modulation of the RTE magnitude is premotor and associated with basic aspects of response selection and preparation.
View details for DOI 10.1016/j.neuroimage.2005.10.023
View details for Web of Science ID 000236894800030
View details for PubMedID 16356737
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Visuoperceptual learning in alcoholic Korsakoff syndrome
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2006; 30 (4): 680-687
Abstract
Relative to the characteristically profound deficits of explicit memory, components of implicit memory remain largely intact in patients with alcohol-induced Korsakoff syndrome (KS). Perceptual priming occurs in KS and transfer of learning has been consistently observed on mirror reading, a perceptual reversal task. Although priming also occurs with fragmented pictures, a perceptual closure task, it is unclear whether transfer of learning can occur. This study examined visuoperceptual learning in 4 men with alcoholic KS, 9 recently detoxified alcoholic men (ALC), 21 healthy age-matched normal control men (NC), and 6 young normal control men (YNC). Subjects were tested with the Gollin Incomplete Pictures Test at initial and 1-hour and 1-day retest sessions. Both alcoholic groups (KS, ALC) were impaired in visuoperceptual ability. All subject groups showed visuoperceptual learning. The KS group showed additional learning after continued exposure to the stimuli, despite their nonmnemonic visuospatial deficits and profound explicit memory impairment for the test stimuli. Transfer of learning to similar but new stimuli was not evident in either the KS or young healthy control subjects; learning occurred only for the specific items presented. The persistence of learning beyond the life of the percept, which was independent of declarative features (such as item recall), suggests that perceptual learning and memory reflects an intact cognitive memory process in KS. This process is likely mediated by posterior cortical networks relatively unaffected in KS and that are independent of the hippocampal-diencephalic declarative memory system.
View details for DOI 10.1111/j.1530-0277.2006.00085.x
View details for Web of Science ID 000236756300013
View details for PubMedID 16573587
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Deformation-based brain morphometry to track the course of alcoholism: Differences between intra-subject and inter-subject analysis
PSYCHIATRY RESEARCH-NEUROIMAGING
2006; 146 (2): 157-170
Abstract
Substantial changes in brain morphology mark the course of alcoholism from development through dependence, recovery, and relapse. These changes can be characterized with deformation-based morphometry, which quantifies shape differences between anatomical structures, either in different subjects (cross-sectional) or in the same subject over time (longitudinal). Here we present analyses of data from a longitudinal magnetic resonance imaging (MRI) study on the effects of alcoholism on brain structure. Images were acquired from alcoholic women (n=7, mean age 47.8+/-8.3 years) and age-matched control women (n=16, mean age 51.2+/-7.5 years). From each subject, we acquired two structural MR brain images, separated by approximately 2 years (mean 21.6+/-7 months). We performed two types of morphometry using log-Jacobian maps of inter-subject and intra-subject nonrigid coordinate transformations, justified by the invariance of relevant statistics (mean, standard deviation, z-score, and t-test) under changes of the spatial and temporal reference coordinate system. With all images from one time point, a cross-sectional inter-subject morphometry determined group differences between alcoholics and normal controls. We compared these results with longitudinal intra-subject morphometry based on two images per subject acquired at different times (approximately 2 years apart). Inter- and intra-subject analysis produced partially conflicting results. Whereas the intra-subject analysis indicated faster ventricular volume increases in the alcoholics (+11% per year) than in the controls (+2% per year), the inter-subject analysis showed, on average, smaller absolute ventricle volumes in the alcoholics than in the controls (-33% relative volume). These differences were confirmed by manual planimetry and were statistically significant whether tested based on difference or change, integrated over the volume of the ventricles. Other changes and group differences were consistent between the two analyses, e.g., reduction of white matter (including corpus callosum) and increase in CSF volume, and these are in agreement with established effects of alcoholism on brain structure. We conclude that intra-subject morphometry of longitudinal data is preferable to inter-subject morphometry for detecting dynamic changes due to a disease, especially when only small samples are available. Our analysis demonstrates that the distinction between group differences observed at a point in time vs. over time is not merely academic but can substantially reduce the validity of the outcomes of actual morphometric studies. This discrepancy in results underscores the importance of distinguishing between volume differences and volume changes in morphometric analyses.
View details for DOI 10.1016/j.pscychresns.2005.12.002
View details for Web of Science ID 000237123700006
View details for PubMedID 16500088
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Supratentorial profile of white matter microstructural integrity in recovering alcoholic men and women
BIOLOGICAL PSYCHIATRY
2006; 59 (4): 364-372
Abstract
Postmortem and in vivo studies consistently report degeneration of brain white matter in alcohol-dependent men and women. The full extent of the white matter involvement in uncomplicated alcoholism, however, is unknown, yet knowledge of the distribution of white matter degradation might provide clues to mechanisms underlying the pathology.To examine whether the white matter involvement is widespread or, alternatively, is regionally restricted in uncomplicated alcoholism, we used in vivo magnetic resonance diffusion tensor imaging (DTI) to quantify the microstructure of brain tissue. Accordingly, we acquired DTI data in 57 alcoholics (40 men, 17 women) who had been sober, on average, for 3 months and 74 demographically-matched control subjects (32 men, 42 women). Alcoholic men had consumed about twice as much alcohol in their lifetimes as the alcoholic women. Supratentorial white matter fractional anisotropy (FA), a DTI measure of intravoxel orientational coherence of tissue, was calculated across the full anterior-posterior extent of the brain in coronal sections, and a slice profile of the mean white matter FA was created for each subject. Group differences between alcoholics and control subjects were tested for each slice in three regions: the left and right hemispheres and a midsagittal sample; men and women were tested separately.Alcoholic men and women each showed widespread FA deficits in all three regions relative to their gender-matched control subjects that were evident on a slice-by-slice basis. Furthermore, the number of slices showing FA deficits was significantly greater in the alcoholic men than women.The widespread distribution of white matter deficits is in contrast to the highly regional-specific deficits seen in nutritional deficiency syndromes that can accompany alcoholism.
View details for DOI 10.1016/j.biopsych.2005.06.025
View details for Web of Science ID 000235670800010
View details for PubMedID 16125148
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Diffusion tensor imaging and aging
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
2006; 30 (6): 749-761
Abstract
Magnetic resonance diffusion tensor imaging (DTI) is a non-invasive in vivo method for characterizing the integrity of anatomical connections and white matter circuitry and provides a quantitative assessment of the brain's white matter microstructure. DTI studies reveal age-related declines in white matter fractional ansiotropy (FA) in normal healthy adults in whom volume declines are not necessarily detectable. The decline is equivalent in men and women, is linear from about age 20 years onwards, and has a frontal distribution. Studies combining regional DTI metrics and tests of specific cognitive and motor functions have shown that age-related declines in white matter integrity are associated with similar declines in interhemispheric transfer, especially dependent on frontal systems. Emerging from recent DTI findings and conceptualizations of neural causes of cognitive decline in aging, we propose three white matter-mediated neural system hypotheses of aging brain structure and function: (1) the anteroposterior gradient, (2) bilateral recruitment of brain systems via the corpus callosum for frontally based task execution, and (3) frontocerebellar synergism. These hypotheses are not mutually exclusive but establish a basis for posing testable questions about brain systems recruited when those used in youth are altered by aging.
View details for DOI 10.1016/j.neubiorev.2006.06.002
View details for Web of Science ID 000241208800004
View details for PubMedID 16887187
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Frontal, parietal, and callosal degradation in aging: A quantitative DTI fiber tracking study
44th Annual Meeting of the American-College-Neuropsychopharmacology
NATURE PUBLISHING GROUP. 2005: S80–S81
View details for Web of Science ID 000233442100222
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Regional striatal volume abnormalities in schizophrenia: Effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type
59th Annual Meeting of the Society-of-Biological-Psychiatry
ELSEVIER SCIENCE BV. 2005: 189–200
Abstract
Striatal structures form critical nodes of multiple circuits that are implicated in the pathophysiology of schizophrenia and alcoholism. Here, we examined the separate and combined effects of schizophrenia and alcoholism and effects of medication type and drinking recency on striatal volumes. Accordingly, we measured caudate nucleus, putamen, and nucleus accumbens in 27 schizophrenic, 25 alcohol-dependent, 19 comorbid (schizophrenia and alcohol dependence or abuse), and 51 age-matched control men. Schizophrenics were classified by antipsychotic medication (typical or atypical), and alcoholics were classified by recency of sobriety. All measured structures were smaller in the patient groups than the control group. The caudate deficit was comparable across groups, whereas putamen and nucleus accumbens deficits were greater in schizophrenia than alcoholism; comorbids fell between these groups. Schizophrenic patients treated with atypical medication showed greater volume deficits in the putamen than those treated with typical medication. Recently sober (<3 weeks) alcoholics had greater deficits in nucleus accumbens than longer sober drinkers. In conclusion, caudate, putamen, and nucleus accumbens exhibited different patterns of volume deficit in patients with alcoholism and schizophrenia alone, with no evidence for compounded deficits in comorbid patients. Further, these cross-sectional data provide indirect support for at least partial recovery of nucleus accumbens volume with sobriety in alcoholics, regardless of schizophrenia comorbidity.
View details for DOI 10.1016/j.schres.2005.04.025
View details for Web of Science ID 000233074600005
View details for PubMedID 15963693
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Corpus callosal microstructural integrity influences interhemispheric processing: A diffusion tensor imaging study
CEREBRAL CORTEX
2005; 15 (9): 1384-1392
Abstract
Normal aging and chronic alcoholism result in disruption of brain white matter microstructure that does not typically cause complete lesions but may underlie degradation of functions requiring interhemispheric information transfer. We examined whether the microstructural integrity of the corpus callosum assessed with diffusion tensor imaging (DTI) would relate to interhemispheric processing speed. DTI yields estimates of fractional anisotropy (FA), a measure of orientation and intravoxel coherence of water diffusion usually in white matter fibers, and diffusivity (
), a measure of the amount of intracellular and extracellular fluid diffusion. We tested the hypothesis that FA and would be correlated with (i) the crossed-uncrossed difference (CUD), testing visuomotor interhemispheric transfer; and (ii) the redundant targets effect (RTE), testing parallel processing of visual information presented to each cerebral hemisphere. FA was lower and higher in alcoholics than in controls. In controls but not alcoholics, large CUDs correlated with low FA and high in total corpus callosum and regionally in the genu and splenium. In alcoholics but not controls, small RTEs, elicited with equiluminant stimuli, correlated with low FA in genu and splenium and high in the callosal body. The results provide in vivo evidence for disruption of corpus callosum microstructure in normal aging and alcoholism that has functional ramifications for efficiency in interhemispheric processing. View details for DOI 10.1093/cercor/bhi020
View details for Web of Science ID 000231296900010
View details for PubMedID 15635059
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Neurocircuitry in alcoholism: a substrate of disruption and repair
PSYCHOPHARMACOLOGY
2005; 180 (4): 583-594
Abstract
The chronic, excessive consumption of alcohol results in significant modification of selective neural systems of the brain structure, physiology, and function. Quantitative MR structural imaging, diffusion tensor imaging (DTI), and functional MRI (fMRI), together with neuropsychological challenges, have enabled rigorous in vivo characterization of the results of alcoholism on the brain in the human condition. Neuroimaging has also enabled longitudinal study for the examination of alcoholism's dynamic course through periods of drinking and sobriety. Controlled studies have revealed compelling evidence for alcohol-related brain structural and functional modification--some longstanding, some transient, and some compensatory. Patterns of circuitry disruption identified through structural and functional MRI studies suggest a central role for degradation of frontocerebellar neuronal nodes and connecting circuitry affecting widespread brain regions and contributing to alcoholism's salient, enduring, and debilitating cognitive and motor deficits--executive dysfunction, visuospatial impairment, and ataxia.
View details for DOI 10.1007/s00213-005-2267-6
View details for Web of Science ID 000231731800002
View details for PubMedID 15834536
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Alcoholic neurobiology: Changes in dependence and recovery
12th International Congress of the International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL. 2005: 1504–13
Abstract
This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October, 2004. Chronic alcoholism follows a fluctuating course, which provides a naturalistic experiment in vulnerability, resilience, and recovery of human neural systems in response to presence, absence, and history of the neurotoxic effects of alcoholism. Alcohol dependence is a progressive chronic disease that is associated with changes in neuroanatomy, neurophysiology, neural gene expression, psychology, and behavior. Specifically, alcohol dependence is characterized by a neuropsychological profile of mild to moderate impairment in executive functions, visuospatial abilities, and postural stability, together with relative sparing of declarative memory, language skills, and primary motor and perceptual abilities. Recovery from alcoholism is associated with a partial reversal of CNS deficits that occur in alcoholism. The reversal of deficits during recovery from alcoholism indicates that brain structure is capable of repair and restructuring in response to insult in adulthood. Indirect support of this repair model derives from studies of selective neuropsychological processes, structural and functional neuroimaging studies, and preclinical studies on degeneration and regeneration during the development of alcohol dependence and recovery form dependence. Genetics and brain regional specificity contribute to unique changes in neuropsychology and neuroanatomy in alcoholism and recovery. This symposium includes state-of-the-art presentations on changes that occur during active alcoholism as well as those that may occur during recovery-abstinence from alcohol dependence. Included are human neuroimaging and neuropsychological assessments, changes in human brain gene expression, allelic combinations of genes associated with alcohol dependence and preclinical studies investigating mechanisms of alcohol induced neurotoxicity, and neuroprogenetor cell expansion during recovery from alcohol dependence.
View details for DOI 10.1097/01.alc.0000175013.50644.61
View details for Web of Science ID 000231767900018
View details for PubMedID 16156047
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Cortical NAA deficits in HIV infection without dementia: Influence of alcoholism comorbidity
NEUROPSYCHOPHARMACOLOGY
2005; 30 (7): 1392-1399
Abstract
Alcoholism comorbidity is highly prevalent in individuals infected with human immunodeficiency virus (HIV). Each condition is known to affect brain structure, function, and metabolism, but the combined effects on the brain have only recently been considered. Single-voxel, proton MR spectroscopy (MRS) has yielded sensitive measures of early brain deterioration in the progression of HIV, but has limited coverage of neocortex, whereas MRS imaging (MRSI) can simultaneously interrogate large regions of cortex. Included were 15 men with HIV+alcoholism, nine men with HIV alone, eight men with alcoholism alone (abstinent for 3-17 months), and 23 controls. The two HIV groups were matched in T-cell count and were not demented; the two alcoholism groups were relatively matched in lifetime alcohol consumption. We used MRSI with a variable-density spiral sequence to quantify major proton metabolites--N-acetylaspartate (NAA), creatine (Cr), and choline (Cho)-in the superior parietal-occipital cortex. Metabolites were expressed in absolute units and as the NAA/Cr ratio. Significant group effects were present for NAA and Cr. Only the HIV+alcoholism group was significantly affected, exhibiting a 0.8 SD deficit in NAA and a 1.0 SD deficit in Cr. The deficits were not related to highly active antiretroviral therapy (HAART) status. Neither HIV infection nor alcoholism independently resulted in parietal-occipital cortical metabolite abnormalities, yet each disease carried a liability that put affected individuals at a heightened risk of neuronal compromise when the diseases were compounded. Further, the use of absolute measures revealed deficits in NAA and Cr that would have gone undetected if these metabolites were expressed as a ratio.
View details for DOI 10.1038/sj.npp.1300723
View details for Web of Science ID 000229881800017
View details for PubMedID 15812566
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Differentiating pathologic delta from healthy physiologic delta in patients with Alzheimer disease
SLEEP
2005; 28 (7): 865-870
Abstract
In patients with Alzheimer disease, the electroencephalogram during wakefulness shows pathologic signs of abundant, diffuse, large-amplitude delta activity. The carryover of this abnormal delta activity into non-rapid eye movement sleep raises the question of whether the observed delta electroencephalographic activity during sleep in Alzheimer disease in any way reflects normal physiologic delta activity slow-wave sleep. The objective of the study was to compare patients with Alzheimer disease with age-matched controls using an experimentally controlled procedure that can test the capacity of the nervous system to generate physiologic delta-frequency responses during sleep.Research sleep laboratory.Seven ambulatory patients with Alzheimer disease (mean age = 70.0 +/- 5.77 years) meeting the National Institute of Neurological and Communicative Diseases and Stroke and Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease and 8 controls (mean age = 69.25 +/- 4.95 years), underwent at least 1 night of evoked-potential recordings.Data were collected during stage 2 sleep. Responses to stimuli were classified based on whether they produced a K-complex. Averages of K-complex responses were calculated, latencies and amplitudes of components evaluated, and K-complex incidence was determined. Relative to controls, subjects with Alzheimer disease produced significantly fewer evoked K-complexes (P < .001) and had substantially smaller N550 amplitudes than controls (P < .05). A lower probability of eliciting a K-complex correlated with greater dementia severity, as measured by the Mini Mental State Examination and Dementia Rating Scale.Despite observed increases in pathologic delta-frequency electroencephalographic activity, patients with Alzheimer disease have an impaired capacity to generate normal physiologic delta responses during non-rapid eye movement sleep.
View details for Web of Science ID 000230501700016
View details for PubMedID 16124667
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Preservation of hippocampal volume throughout adulthood in healthy men and women
NEUROBIOLOGY OF AGING
2005; 26 (7): 1093-1098
Abstract
To address controversies regarding the effect of age on the hippocampus, volumes of hippocampus and a comparison structure, temporal cortex, were measured on magnetic resonance imaging (MRI) in 84 healthy men and 44 healthy women (20-85 years). Neither men nor women showed significant correlations between hippocampal volumes and age, despite significant age-related decline in temporal volumes. Absence of hippocampus age relationships endured when restricting analyses to older individuals (> or =50 years) and considering menopause and hormone replacement therapy.
View details for DOI 10.1016/j.neurobiolaging.2004.09.015
View details for Web of Science ID 000227821000014
View details for PubMedID 15748789
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Frontal circuitry degradation marks healthy adult aging: Evidence from diffusion tensor imaging
NEUROIMAGE
2005; 26 (3): 891-899
Abstract
In vivo study of white matter microstructural integrity through magnetic resonance diffusion tensor imaging (DTI) permits examination of degradation of axonal circuitry that may underlie functional decline of frontally-based processes in normal adult aging. Determination of the pattern of age-related degradation of white matter microstructure requires quantitative comparison of the rostral-caudal and superior-inferior extents of the brain's white matter. To date, this has not been accomplished, probably because of significant artifacts from spatial distortion and poor signal resolution that precludes accurate analysis in prefrontal and inferior brain regions. Here, we report a profile analysis of the integrity of white matter microstructure across the supratentorium and in selected focal regions using DTI data collected at high-field strength (3 T), with isotropic voxel acquisition, and an analysis based on a concurrently-acquired field map to permit accurate quantification of artifact-prone, anterior and inferior brain regions. The groups comprised 10 younger and 10 older individuals; all were high functioning, highly educated, and in excellent health. The DTI profile analysis revealed a robust frontal distribution of low white matter anisotropy and high bulk mean diffusivity in healthy older compared with younger adults. In contrast to frontal fiber systems, posterior systems were largely preserved with age. A second analysis, based on focal samples of FA, confirmed that the age-related FA decline was restricted to frontal regions, leaving posterior and inferior brain regions relatively intact. The selective decline of anterior anisotropy with advancing age provides evidence for the potential of a microstructural white matter mechanism for the commonly observed decline in frontally-based functions.
View details for DOI 10.1016/j.neuroimage.2005.02.034
View details for Web of Science ID 000230211100025
View details for PubMedID 15955499
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The pathophysiology of 'brain shrinkage' in alcoholics - Structural and molecular changes and clinical implications
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2005; 29 (6): 1106-1115
View details for DOI 10.1097/01.ALC.0000171490.09017.A9
View details for Web of Science ID 000230212900023
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Story recall improves with abstinence in chronic alcoholic men and women
28th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2005: 68A–68A
View details for Web of Science ID 000229375900370
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White matter tract integrity and information transmission in alcoholism: A diffusion tensor imaging and event-related potential study
28th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2005: 126A–126A
View details for Web of Science ID 000229375901127
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Patterns of subcortical volume deficits in Alzheimer's disease and Korsakoff's syndrome
60th Annual Convention of the Society-of-Biological-Psychiatry
ELSEVIER SCIENCE INC. 2005: 161S–161S
View details for Web of Science ID 000228338601183
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Striatal and forebrain nuclei volumes: Contribution to motor function and working memory deficits in alcoholism
BIOLOGICAL PSYCHIATRY
2005; 57 (7): 768-776
Abstract
Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholism's effect on volumes of these structures has seldom been considered with in vivo measurement.We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men. Six alcoholic subjects had been drinking recently, and 19 had been sober.Volumes of caudate and putamen were smaller in the alcoholics than in the control subjects, regardless of length of sobriety. Recent drinkers showed greater deficits in nucleus accumbens than sober alcoholics. Putamen volume was positively correlated with grip strength; MS/DB volume was positively correlated with verbal working memory independently of the negative association between age-standardized MS/DB and age in alcoholics.Caudate and putamen volume deficits occur and endure in chronic alcoholism. Nucleus accumbens might be especially sensitive to recent alcohol exposure. Striatal volumes should be considered in functional imaging studies of alcohol craving that target striatal brain regions. The age-alcohol interaction for MS/DB volumes is consistent with a cholinergic mechanism for the working memory impairment observed in the alcoholics.
View details for DOI 10.1016/j.biopsych.2004.12.012
View details for Web of Science ID 000228125000011
View details for PubMedID 15820234
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Persistent cognitive deficits in community-treated alcoholic men and women volunteering for research: Limited contribution from psychiatric comorbidity
JOURNAL OF STUDIES ON ALCOHOL
2005; 66 (2): 254-265
Abstract
The contribution of psychiatric comorbidity to cognitive status was assessed in a sample of treatment-seeking alcoholics who met criteria to participate in studies of effects of chronic alcohol misuse on brain structure and cognition.Alcoholic men (n = 43) and women (n = 21) who responded to notices about a research study were screened, clinically assessed and administered Wechsler Memory and Intelligence tests after 3 months of sobriety, on average. Cognitive performance was compared with that of an age-matched sample of healthy controls (n = 51).As a group, the alcoholics achieved significantly lower scores than controls on summary indices of the Wechsler Memory and Adult Intelligence Scales and showed greater decline from estimated premorbid intelligence levels than controls. Almost 60% of the alcoholics had at least one additional psychiatric (mood or anxiety) or past substance-dependence comorbidity. There were no marked sex differences in patterns of comorbidity. Comorbid alcoholics were younger, had consumed less alcohol over their lifetime and performed between noncomorbid alcoholics and controls on all tests.Mood and anxiety comorbidity did not necessarily compound poor cognitive test performance associated with chronic alcohol misuse. While unexpected, this finding suggests that, in this sample, poorer cognitive performance was more a function of alcoholism per se than nonalcoholic comorbidity.
View details for Web of Science ID 000229028100012
View details for PubMedID 15957677
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Neuroimaging of rodent and primate models of alcoholism: Initial reports from the integrative neuroscience initiative on alcoholism
27th Annual Meeting of the Research-Society-on-Alcoholism
BLACKWELL PUBLISHING. 2005: 287–94
Abstract
Neuroimaging of animal models of alcoholism offers a unique path for translational research to the human condition. Animal models permit manipulation of variables that are uncontrollable in clinical, human investigation. This symposium, which took place at the annual meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada, on June 29th, 2004, presented initial findings based on neuroimaging studies from the two centers of the Integrative Neuroscience Initiative on Alcoholism funded by the National Institute on Alcohol Abuse and Alcoholism. Effects of alcohol exposure were assessed with in vitro glucose metabolic imaging of rat brain, in vitro receptor imaging of monkey brain, in vivo magnetic resonance imaging of monkey brain, and in vivo magnetic resonance spectroscopic quantification of alcohol metabolism kinetics in rat brain.
View details for DOI 10.1097/01.ALC.0000153546.39946.EC
View details for Web of Science ID 000227221700013
View details for PubMedID 15714052
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Disruption of brain white matter microstructure by excessive intracellular and extracellular fluid in alcoholism: Evidence from diffusion tensor imaging
NEUROPSYCHOPHARMACOLOGY
2005; 30 (2): 423-432
Abstract
Magnetic resonance diffusion tensor imaging (DTI) has revealed the disruption of brain white matter microstructure in normal aging and alcoholism undetectable with conventional structural MR imaging. The metrics of DTI can be useful in establishing the nature of the observed microstructural aberrations. Abnormally low fractional anisotropy (FA), a measure of diffusion orientation and coherence, may result from increased intracellular or extracellular fluid, which would be reflected in complementary high apparent diffusion coefficients (bulk mean diffusivity) and low FA, or from disorganization of fiber structure, which would be reflected in low FA but with a lack of the inverse FA and diffusivity relationship. To test these competing possibilities, we examined 15 alcoholic men and 31 control men with DTI to quantify diffusivity in the genu and splenium of the corpus callosum and centrum semiovale. In addition to the previously observed FA deficits in all the three brain regions, the alcoholics had abnormally high white matter diffusivity values in the genu and centrum. Further, inverse correlations between FA and diffusivity were significant in the genu (r=-0.52, p<0.05) and centrum (r=-0.92, p=0.0001). Multiple regression analyses examining diffusivity and age as predictors of FA identified diffusivity as a significant unique contributor to FA in both regions. These results suggest that decreased orientational coherence of brain white matter in alcoholism is attributable, at least in part, to the accumulation of intracellular and extracellular fluid in excess of that occurring in aging, and that the differential influence of these fluid compartments can vary across brain regions.
View details for DOI 10.1038/sj.npp.1300623
View details for Web of Science ID 000226569900022
View details for PubMedID 15562292
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Information fusion in biomedical image analysis: combination of data vs. combination of interpretations.
Information processing in medical imaging : proceedings of the ... conference
2005; 19: 150-161
Abstract
Information fusion has, in the form of multiple classifier systems, long been a successful tool in pattern recognition applications. It is also becoming increasingly popular in biomedical image analysis, for example in computer-aided diagnosis and in image segmentation. In this paper, we extend the principles of multiple classifier systems by considering information fusion of classifier inputs rather than on their outputs, as is usually done. We introduce the distinction between combination of data (i.e., classifier inputs) vs. combination of interpretations (i.e., classifier outputs). We illustrate the two levels of information fusion using four different biomedical image analysis applications that can be implemented using fusion of either data or interpretations: atlas-based image segmentation, "average image" tissue classification, multi-spectral classification, and deformation-based group morphometry.
View details for PubMedID 17354692
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Information fusion in biomedical image analysis: Combination of data vs. combination of interpretations
19th International Conference on Information Processing in Medical Imaging
SPRINGER-VERLAG BERLIN. 2005: 150–161
View details for Web of Science ID 000230871900013
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Cortical grey matter volume and sleep ERP amplitude in normal aging and alcoholism
WILEY-BLACKWELL. 2005: 32–32
View details for Web of Science ID 000234555700107
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Differential effect of HIV infection and alcoholism on conflict processing, attentional allocation, and perceptual load: Evidence from a Stroop Match-to-Sample task
BIOLOGICAL PSYCHIATRY
2005; 57 (1): 67-75
Abstract
Alcoholism and human immunodeficiency virus (HIV) infection each can impair components of selective attention, probably through disruption of the integrity of the frontoparietal neural systems that underlie conflict processing, attentional allocation, and perceptual load.We studied 18 patients with alcoholism (ALC) alone, 19 with HIV infection alone (HIV), 20 with both disorders (H+A), and 19 healthy control subjects (CTL). We used a novel paradigm (Stroop Match-to-Sample tasks), in which subjects saw either a valid or invalid color cue before a target word, printed in a color that was either congruent or incongruent with the word's meaning.All groups showed a significant Stroop effect, cue-target color Match effect, and interaction between Match and Stroop, with an exaggerated Stroop effect for the Match condition. The HIV patients were comparable to CTL, whereas ALC showed mild delays, with further delays associated with comorbidity with HIV. Although H+A profited from a valid match to Stroop stimuli, they were compromised in disengaging attention from the invalidly cued color.Impairment in conflict processing and attentional allocation in alcoholism suggests disruption of frontal-parietal attentional systems. Although HIV alone did not demonstrate detectable impairment in performance, HIV conferred liability on attentional processes when combined with alcohol abuse.
View details for DOI 10.1016/j.biopsych.2004.09.025
View details for Web of Science ID 000226421800010
View details for PubMedID 15607302
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Parietal-occipital cortical NAA deficits in HIV-Infected men comorbid for alcoholism
43rd Annual Meeting of the American-College-of-Neuropsychopharmacology
NATURE PUBLISHING GROUP. 2004: S185–S186
View details for Web of Science ID 000225588000535
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Striatal volume deficits in alcoholism with and without Korsakoff's syndrome
43rd Annual Meeting of the American-College-of-Neuropsychopharmacology
NATURE PUBLISHING GROUP. 2004: S188–S188
View details for Web of Science ID 000225588000545
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In vivo structural imaging of the rat brain with a 3-T clinical human scanner
JOURNAL OF MAGNETIC RESONANCE IMAGING
2004; 20 (5): 779-785
Abstract
To examine the feasibility of using product acquisition software on a 3-T human MRI system to acquire high-resolution structural brain images in the rat.Three sets of dual spin-echo, high-resolution (0.234 x 0.234 mm in-plane, 0.5 mm thick) images covering the entire rat brain were collected and averaged in 66 min. The images had sufficient signal-to-noise ratio (SNR) and resolution for visual identification and manual outlining of exemplary structures, including the lateral ventricles and dorsal and ventral portions of the hippocampus. Further, the data were adequate for unsupervised, automated segmentation, permitting quantification of the dorsolateral ventricles. The images compared favorably with those collected on a 7-T system.Interrater reliabilities (intraclass correlations) of manual ventricular scoring were greater than 0.97, and manual vs. automated correlations were 0.97. The variability of lateral ventricular size across animals was substantially higher than that of the hippocampus.The large variability of some brain structures that can exist across even a highly selected strain of rats can readily be detected with the use of human 3-T systems for the study of small animals.
View details for DOI 10.1002/jmri.20181
View details for Web of Science ID 000224762700006
View details for PubMedID 15503335
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Perceptual learning in detoxified alcoholic men: Contributions from explicit memory, executive function, and age
32nd Annual Meeting of the International-Neuropsychological-Society
WILEY-BLACKWELL PUBLISHING, INC. 2004: 1657–65
Abstract
Visuospatial and visuoperceptual deficits have consistently been observed in detoxified alcoholics; however, the severity of impairment varies with test and task type. Identifying the component processes and factors that underlie a particular deficit may reveal why some visuospatial and visuoperceptual tasks are more compromised than others and may lead to the specification of neural systems that are particularly vulnerable in alcoholism.We examined visuoperception and perceptual learning with a picture fragment identification task in 51 recently detoxified nonamnesic alcoholic men (aged 29-66 years) compared with 63 normal control men (aged 21-70 years). Executive function and explicit declarative memory were also assessed.Despite deficits in the primary components of visuoperception and explicit memory for visuospatial stimuli, the alcoholics showed normal perceptual learning. Although the alcoholics and controls performed at comparable levels on the perceptual learning task, multiple regression analyses indicated that the factors accounting for perceptual learning variance differed between and within groups. Visuoperceptual abilities consistently predicted perceptual learning in the control subjects but not the alcoholic subjects. Explicit memory contributed to perceptual learning performance in both the alcoholic and control groups. Frontal executive ability consistently predicted perceptual learning in the alcoholic subjects, but it had predictive ability only in the control subjects as time elapsed. Age was significantly correlated with perceptual learning performance in both groups. Lifetime alcohol consumption, but not alcoholism duration, was an independent predictor of 1-hr perceptual learning.These correlational analyses suggest that controls invoke basic visuospatial processes to perform a perceptual learning task, whereas alcoholics invoke higher-order cognitive processes (i.e., frontal executive systems) to perform the same task at normal levels. Use of more demanding cognitive systems by the alcoholics may be less efficient and more costly to processing capacity than those invoked by controls.
View details for DOI 10.1097/01.ALC.0000145690.48510.DA
View details for Web of Science ID 000225201900009
View details for PubMedID 15547452
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Brain volumes, RBC status, and hepatic function in alcoholics after 1 and 4 weeks of sobriety: Predictors of outcome
AMERICAN JOURNAL OF PSYCHIATRY
2004; 161 (7): 1190-1196
Abstract
The authors asked if hematological indices of RBC status and hepatic function in newly sober alcoholic men are related to abnormalities in brain morphology, change with normalization of brain function during short-term sobriety, and predict prolonged sobriety.Alcoholic men received brain magnetic resonance imaging and laboratory assessments on admission and before discharge from an inpatient treatment program. Healthy comparison men were similarly tested.On admission, RBC count, hemoglobin level, and hematocrit were significantly lower in alcoholic subjects than comparison subjects; mean corpuscular volume, SGOT, SGPT, and gamma-glutamyl transpeptidase were significantly higher. By discharge, all measures had improved, although RBC count, mean corpuscular volume, and gamma-glutamyl transpeptidase levels remained significantly different from those of comparison subjects. Upon admission, alcoholic men had smaller cortical white and gray matter and larger lateral and third ventricle volumes, with reduced lateral ventricle and increased anterior cortical gray matter volumes by discharge. Lower RBC count, hemoglobin level, and hematocrit were associated with lower white matter and higher ventricular volumes at admission. Change in these measures was related to reduction in ventricular volume with treatment. By discharge, associations among RBC count, hemoglobin level, and hematocrit and white matter and ventricular volumes were less marked than at admission. Discharge hemoglobin value and hematocrit discriminated patients who maintained sobriety from those who relapsed. Hepatic function showed limited association with brain measures at admission and discharge.Hemograms reflect alcohol-related abnormalities in brain morphology, improvement over short-term sobriety, and liability to relapse after treatment.
View details for Web of Science ID 000222462700008
View details for PubMedID 15229050
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Recovery of short-term memory and psychomotor speed but not postural stability with long-term sobriety in alcoholic women
25th Annual Meeting of the Research-Society-on-Alcoholism
AMER PSYCHOLOGICAL ASSOC. 2004: 589–97
Abstract
The authors assessed effects of extended abstinence on cognitive and motor function deficits previously observed in a group of alcoholic women (n = 43) initially tested after 15 weeks of sobriety. Alcoholic women were retested 1 and 4 years later, and control women were retested 3 years later. At Year 1, 14 of 23 returners had maintained sobriety, but they did not perform significantly better than relapsers; the group as a whole continued to show deficits relative to age norms. By Year 4, 13 of 14 returners had maintained sobriety for more than 30 months; as a group, these women had returned to normal levels on tests of memory and psychomotor speed but remained impaired in standing balance.
View details for DOI 10.1037/0894-4105.18.3.589
View details for Web of Science ID 000222706700020
View details for PubMedID 15291737
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In vivo 2D J-resolved magnetic resonance spectroscopy of rat brain with a 3-T clinical human scanner
NEUROIMAGE
2004; 22 (1): 381-386
Abstract
A clinical 3-T scanner equipped with a custom-made transmit/receive birdcage coil was used to collect 2D J-resolved single-voxel spectroscopy in vivo of rat brain. Four adult Wistar rats were scanned twice each, with a 2-week interval. Voxel size was approximately 5 x 10 x 5 mm(3). Total spectroscopic acquisition time was 14 min for collection of two 4:20 min water-suppressed acquisitions and one 4:20 min acquisition acquired in the absence of water suppression. The unsuppressed water data were used in post-processing to reduce residual water side bands, as well as for metabolite signal normalization to account for variations in coil loading and voxel size. Peak areas were estimated for resonances from N-acetyl aspartate (NAA), creatine, choline, taurine, glutamate, and combined glutamate and glutamine. T(2)-relaxation times were estimated for NAA and creatine. The average deviation from the mean of repeated measures for glutamate, combined glutamate and glutamine, and taurine ranged from 7.6% to 18.3%, while for NAA, creatine, and choline, the deviation was less than 3%. The estimated T(2) values for NAA (mean +/- SD = 330 +/- 57 ms) and creatine (174 +/- 27 ms) were similar to those reported previously for rat brain and for human gray and white matter. These results indicate that reliable, small animal brain MR spectroscopy can be performed on a human clinical 3-T scanner.
View details for DOI 10.1016/j.neuroimage.2003.12.046
View details for Web of Science ID 000221190200039
View details for PubMedID 15110030
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Persistent cognitive deficits in community-treated alcoholics
27th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2004: 145A–145A
View details for Web of Science ID 000221549300832
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Clinical features of community-treated alcoholics volunteering for research
27th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2004: 116A–116A
View details for Web of Science ID 000221549300656
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Differential hemispheric visuospatial functioning in alcoholism, HIV, and their comorbidity
27th Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2004: 151A–151A
View details for Web of Science ID 000221549300865
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Medication but not alcoholism comorbidity contributes to basal ganglia volume deficits in schizophrenia
59th Annual Meeting of the Society-of-Biological-Psychiatry
ELSEVIER SCIENCE INC. 2004: 219S–219S
View details for Web of Science ID 000220755300764
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Postmortem MR imaging of formalin-fixed human brain
41st Annual Meeting of the American-College-of-Neuropsychopharmacology
ACADEMIC PRESS INC ELSEVIER SCIENCE. 2004: 1585–95
Abstract
High-resolution postmortem neuroimaging of the brain can play a role in research programs by providing archival and reslicable images of brain specimens before permanent sectioning. These images can supplement evidence attained from both traditional neuropathological observations and in vivo neuroimaging. Differential brain tissue conspicuity, detectable with MRI, is determined by the density and mobility of water protons. Water content is about 70% in white matter, 80% in gray matter, and 99% in cerebrospinal fluid (CSF). To the extent that brain tissue contrast is determined by the number and microenvironment of water protons, timing parameters of MR image acquisition can interrogate this environment. Because the chemical environment of protons is different in living from dead tissue, optimal temporal imaging parameters, for example, for spin-echo imaging, commonly used for in vivo clinical and research study are different from those best for postmortem imaging. Here, we present a series of observations to identify relaxation times and optimal parameters for high-resolution structural imaging of formalin-fixed postmortem brain tissue using commercially available clinical scanners and protocols. Examples of high-resolution images and results from attempts at diffusion imaging are presented.
View details for DOI 10.1016/j.neuroimage.2003.11.024
View details for Web of Science ID 000220723900036
View details for PubMedID 15050582
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Balance and gait deficits in schizophrenia compounded by the comorbidity of alcoholism
41st Annual Meeting of the American-College-of-Neuropsychopharmacology
AMER PSYCHIATRIC PUBLISHING, INC. 2004: 751–55
Abstract
Alcoholism carries a liability of balance and gait instability that persists with sobriety. Such deficits are less well documented in schizophrenia and may be compounded by comorbidity with alcoholism, which is prevalent in schizophrenia.The authors administered quantitative ataxia tests to 10 patients comorbid for schizophrenia and alcohol dependence/abuse, 10 nonalcoholic patients with schizophrenia, 24 nonschizophrenic patients with alcohol dependence, and 27 age-matched comparison men.All three patient groups were impaired relative to the comparison subjects. The comorbid group was significantly more impaired than the alcoholic group on most tests and was more impaired than the schizophrenia patients, especially when tested with eyes open.Rigorous quantitative testing revealed gait and balance deficits in schizophrenia, even without alcohol dependence, and exacerbated deficits in schizophrenia comorbid with alcoholism. The enhancement of postural stability expected with visual information was dampened in comorbid patients, implicating compromised sensorimotor integrative abilities.
View details for Web of Science ID 000221276200026
View details for PubMedID 15056526
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The human basal forebrain integrates the old and the new
NEURON
2004; 41 (5): 825-837
Abstract
Acquisition of new learning is challenged by the phenomenon of proactive interference (PI), which occurs when previous learning disrupts later learning. Whereas human neuroimaging studies have focused on the cortical contributions to interference resolution, animal studies demonstrate that efficient resolution of PI depends on cholinergic modulation from basal forebrain (BF). Whether the BF promotes PI resolution in humans is unknown. Here, we adapted a PI paradigm from animal studies for use in a functional MRI experiment. During PI resolution, neurologically intact subjects recruited a BF network that included afferent anterior and posterior cortical sites associated with efficient memory acquisition and perceptual processing. Despite normal performance, nonamnesic patients with alcoholism, which is known to disrupt BF function, did not activate a BF network but instead invoked anterior cortical sites traditionally associated with executive function. These results provide evidence for parallel neural systems, each with the potential to resolve interference in the face of competing information.
View details for Web of Science ID 000221458200016
View details for PubMedID 15003180
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Alcoholism damages the brain, but does moderate alcohol use?
LANCET NEUROLOGY
2004; 3 (3): 143-144
View details for Web of Science ID 000220167400014
View details for PubMedID 14980527
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Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability
NEUROBIOLOGY OF AGING
2004; 25 (2): 175-183
Abstract
This longitudinal study used the full twin model to estimate change and stability of genetic contributions to morphology of two brain structures, the corpus callosum and lateral ventricles. The 142 subjects were 34 monozygotic (MZ) and 37 dizygotic (DZ) elderly male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study who underwent brain magnetic resonance imaging twice, separated by a 4-year interval. Genetic factors accounted for a substantial portion of individual differences in the size of the corpus callosum and its substructures and of lateral ventricular size. Longitudinal genetic analyses revealed no significant change in the heritability of these structures and no evidence for new genetic variance at Time 2 not present at Time 1. However, both the callosal and ventricular measures showed evidence for new environmental variance at Time 2 not present at Time 1. Confirming a previously posed hypothesis, the phenotypic correlation between absolute change in height of the corpus callosum and absolute change in ventricular volume was significant. Bivariate genetic analysis estimated a significant genetic correlation between the changes in these two structures and the genetic variance in the change of callosal height was entirely due to genes involved in the expansion of ventricles. Genetic stability was present even in old age when brain and other morphological changes can be rapid and highly variable across individuals, inconsistent with an hypothesis that random DNA damage is the cause of aging.
View details for DOI 10.1016/S0197-4580(03)00045-9
View details for Web of Science ID 000188844200005
View details for PubMedID 14749135
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Effects of age and sex on volumes of the thalamus, pons, and cortex
NEUROBIOLOGY OF AGING
2004; 25 (2): 185-192
Abstract
Volumes of thalamus, pons, cortical gray matter, and white matter were derived from MR brain images of healthy men and women spanning the adult age range in order to delineate patterns of aging and to compare age and sex effects in thalamus and pons with such effects in cortical gray and white matter volumes. Men had larger intracranial volume (ICV) than women, but ICV did not correlate with age in either sex. Thalamic, pontine, and cortical white matter volumes did not differ between men and women once ICV differences were taken into account, but men had more cortical gray matter than women even after accounting for ICV. Volumes of pons and thalamus were associated, independent of ICV, in women but not in men. Thalamic volume declined linearly with age at a similar rate in both men and women, whereas cortical gray matter volume declined more steeply with age in men than women. Both pontine and cortical white matter volumes remained stable across the age span in both men and women.
View details for DOI 10.1016/S0197-4580(03)00044-7
View details for Web of Science ID 000188844200006
View details for PubMedID 14749136
- Brain volumes, blood chemistry, and liver function in alcoholics after one and four weeks of sobriety: Predictors of outcome. American Journal of Psychiatry in press. 2004
- In vivo 2D J-resolved magentic resonance spectroscopy of rat brain with a 3T clinical human scanner. NeuroImage in press. 2004
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Differentiating 'Pathological' delta from healthy 'Physiological' delta in Alzheimer's disease
18th Annual Meeting of the Associated-Professional-Sleep-Societies
AMER ACAD SLEEP MEDICINE. 2004: 133–134
View details for Web of Science ID 000223169400296
- Alcoholic drinking damages the brain; does moderate alcohol use? Lancet Neurology (March) in press. 2004
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Parallel interhemispheric processing in aging and alcoholism: relation to corpus callosum size
NEUROPSYCHOLOGIA
2004; 42 (2): 257-271
Abstract
We tested parallel processing of visual information using the redundant targets effect (RTE) in 12 alcoholics and 13 matched controls. The paradigm was a simple reaction time (RT) task with targets presented in the same (uncrossed), opposite (crossed), or both (redundant) visual-fields. In older alcoholics (>50 years) the RT gain invoked by redundant targets did not exceed probability measures, suggesting compromised interhemispheric processing of parallel information in this subgroup compared with controls or younger alcoholics. The difference between crossed and uncrossed reaction times (CUD), an index of interhemispheric transfer time (ITT), was greater in older than younger subjects. Moreover, the CUD was negatively correlated with the corpus callosum (CC) total area and body in controls, supporting the concept of a structure-function relationship of interhemispheric transfer. This relationship was not found in alcoholics, although the midsagittal area of the CC, genu, and body but not intracranial volume (ICV), was significantly smaller in alcoholics than controls. These results suggest that chronic alcohol abuse together with advancing age exert subtle disruption on parallel interhemispheric processing reliant on callosal connections.
View details for DOI 10.1016/S0028-3932(03)00155-6
View details for Web of Science ID 000187220600012
View details for PubMedID 14644111
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Gray matter-N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis
11th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine
AMER SOC NEURORADIOLOGY. 2003: 1941–45
Abstract
Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS.Volumetric spiral MRSI was used together with high-resolution MR imaging to derive absolute measures of metabolite concentrations separately in normal-appearing supratentorial cerebral gray matter and white matter in five RRMS patients, five SPMS patients, and nine age-matched controls. Structural MR images were segmented into compartments of gray matter, white matter, CSF, and lesions, and metabolite signals per unit of tissue volume were calculated for gray matter and white matter separately.Only the SPMS group had significantly lower NAA concentrations in normal-appearing gray matter compared with concentrations in controls. NAA in normal-appearing white matter was equally reduced in RRMS and SPMS patients. The functional relevance of this brain metabolite measure was suggested by the observed but statistically nonsignificant correlation between higher disability scores on the Expanded Disability Status Scale and lower gray matter NAA concentrations.The otherwise occult abnormality in supratentorial gray matter in SPMS but not RRMS may explain the more severe physical and cognitive impairments afflicting patients with SPMS that do not correlate well with visible lesion burden.
View details for Web of Science ID 000186744800006
View details for PubMedID 14625214
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Replicability of diffusion tensor imaging measurements of fractional anisotropy and trace in brain
JOURNAL OF MAGNETIC RESONANCE IMAGING
2003; 18 (4): 427-433
Abstract
To evaluate within-scanner and between-scanner reliability of fractional anisotropy (FA) and trace (sum of the diagonal elements of the diffusion tensor) as measured by diffusion tensor imaging (DTI).Ten young healthy adults were scanned on three separate days, on two different systems made by the same manufacturer. One scan was acquired at one site, and two scans were acquired on two different occasions on another scanner at another site. Three levels of analysis were used to compare the DTI metrics: 1) a voxel-by-voxel analysis of all supratentorial brain (gray matter + white matter + cerebrospinal fluid) and of supratentorial white matter; 2) a slice-by-slice analysis of supratentorial white matter; and 3) a single-region analysis of the corpus callosum.The voxel-by-voxel analysis of all supratentorial brain found that FA and trace measures and correlations were equivalently and significantly higher within than across scanners. For supratentorial white matter, FA was similar within and across scanners, whereas trace demonstrated across-scanner bias. A similar pattern was observed for the slice-by-slice comparison. For the single-region analysis of the corpus callosum, within-scanner FA and trace measures were highly reproducible for FA (CV = 1.9%) and trace (CV = 2.6%), but both DTI measures showed a systematic mean bias across scanners (CV = 4.5% for FA and CV = 7.5% for trace).These estimates of measurement variation and scanner bias can be used to predict effect sizes for longitudinal and multisite studies using diffusion tensor imaging.
View details for DOI 10.1002/jmri.10377
View details for Web of Science ID 000185630100005
View details for PubMedID 14508779
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Progression in brain abnormalities and illness severity in schizophrenia
16th Congress of the European-College-of-Neuropsychopharmacology
ELSEVIER SCIENCE BV. 2003: S133–S134
View details for Web of Science ID 000185412300060
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Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study
NEUROIMAGE
2003; 19 (4): 1510-1520
Abstract
Although there is clear evidence of alcoholism-related damage to the frontal lobes and cerebellum from neuroimaging, neuropathological, and neuropsychological studies, the functional role of the cerebellum and cerebrocerebellar circuits related to verbal working memory deficits of alcoholics have not been well studied. Alcoholic and nonalcoholic subjects performed a Sternberg verbal working memory task while receiving an fMRI scan in a 3T magnet. This task has been found in previous studies to reliably activate the articulatory control and phonological storage components of the phonological loop (left frontal, left temporal/parietal structures, right superior cerebellar regions) in young healthy controls. We hypothesized that the alcoholics would show a different pattern of activation from the controls, based on the regions of interest (ROIs) identified from a previous study of healthy subjects. Behavioral results showed the alcoholics to be performing at a comparable level to the matched controls in terms of accuracy and median reaction time, with no statistically significant differences. However, analysis of the functional data revealed that the alcoholics exhibited greater activation in the left frontal (BA44/45) and right superior cerebellum (HVI) regions relative to the matched controls. These findings suggest that brain activation in left frontal and right cerebellar regions that support the articulatory control system of verbal working memory may require a compensatory increase in alcoholics in order to maintain the same level of performance as controls.
View details for DOI 10.1016/S1053-8119(03)00102-2
View details for Web of Science ID 000185079000022
View details for PubMedID 12948707
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Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia
8th International Congress on Schizophrenia Research
AMER PSYCHIATRIC PUBLISHING, INC. 2003: 1110–16
Abstract
Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure.Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects.The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons.Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.
View details for Web of Science ID 000183240800014
View details for PubMedID 12777269
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Averaged evoked K-complex amplitude correlates with aging over the adult life-span
17th Annual Meeting of the Associated-Professional-Sleep-Societies
AMER ACAD SLEEP MEDICINE. 2003: A162–A163
View details for Web of Science ID 000182841100404
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Alcoholic men endorse more DSM-IV withdrawal symptoms than alcoholic women matched in drinking history
JOURNAL OF STUDIES ON ALCOHOL
2003; 64 (3): 375-379
Abstract
Given gender differences in alcohol metabolism, drinking patterns and alcohol-related problems, we asked whether men and women recruited for research protocols from treatment programs would meet different subsets of alcohol dependence or withdrawal criteria or differ in current level of functioning.The subjects were 66 men and 62 women meeting DSM-III-R or DSM-IV criteria for alcohol dependence. Gender differences were tested infrequency counts of criteria endorsed and Global Assessment of Functioning (GAF) scores.All seven alcohol dependence criteria were endorsed by 50% of the sample. There were no significant gender differences in frequency of individual criteria endorsed. However, more men than women tended to endorse the withdrawal criterion for alcohol dependence and the tremor criterion for alcohol withdrawal, whereas women had higher GAF scores. When subgroups of men and women were matched on alcohol consumption variables, significantly more men than women endorsed the withdrawal criterion for alcohol dependence and the anxiety criterion for alcohol withdrawal, and women still had significantly higher GAF scores than men.DSM criteria provide a similar characterization of alcohol dependence in male and female research volunteers. Despite this similarity, the DSM criteria were sensitive to gender differences, which can now be challenged with rigorous testing.
View details for Web of Science ID 000183221500009
View details for PubMedID 12817826
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Increased brain white matter diffusivity in normal adult aging: Relationship to anisotropy and partial voluming
MAGNETIC RESONANCE IN MEDICINE
2003; 49 (5): 953-961
Abstract
Diffusion tensor imaging (DTI) was used to examine 1) age-related changes in genu, splenium, and centrum semiovale white matter diffusivity in 64 healthy men and women (age 23-85 years); 2) the relationship between diffusivity (trace) and fractional anisotropy (FA) across and within individuals; and 3) the role of macrostructural and microstructural partial voluming effects on the DTI metrics. Regional differences were greater in FA (approximately 43%) than in trace (approximately 16%). Depending on the region of interest, trace increased with age (r = 0.24 to 0.58) and FA decreased with age (r = -0.29 to -0.79). FA was inversely correlated with trace, even when controlling for age. Histogram analysis of trace and FA following systematic expansion and dilation of the white matter regions demonstrated greater susceptibility of FA than trace to error arising from macrostructural partial voluming, i.e., erroneous inclusion of primarily nonwhite-matter voxels. Three-phase ellipsoid shape analysis revealed that after morphometric erosion the spherical component remained greater in older than younger subjects in the splenium and centrum, suggesting that age-related reduction in FA arises from intravoxel increased interstitial fluid. Reducing the size of the white matter samples to control for macrostructural partial voluming attenuated but did not negate effects, indicating that observed changes in white matter with aging can reflect real microstructural alterations rather than sampling artifact. Morphological dilation of white matter regions of interest resulting in purposeful inclusion of non-white matter pixels significantly reduced mean FA, suggesting that reports of FA values below 0.25 in healthy adults may reflect partial voluming rather than actual changes in white matter coherence.
View details for DOI 10.1002/mrm.10452
View details for Web of Science ID 000182642400022
View details for PubMedID 12704779
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Compounded brain volume deficits in schizophrenia-alcoholism comorbidity
38th Annual Meeting of the American-College-of-Neuropsychopharmacology
AMER MEDICAL ASSOC. 2003: 245–52
Abstract
Schizophrenia and alcoholism are characterized by brain volume abnormalities. Despite the frequent comorbidity of these conditions, the potentially compounded effects of comorbidity on brain structure have seldom been rigorously assessed.To determine the compounding effect of schizophrenia and alcoholism on regional brain volumes, we performed retrospective quantitative analysis of magnetic resonance images from men who participated in research protocols at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. Participants were selected on the basis of diagnostic criteria, yielding 4 comparison groups: 35 men comorbid for DSM-III-R schizophrenia or schizoaffective disorder and lifetime alcohol abuse or dependence; 64 men with DSM-III-R schizophrenia or schizoaffective disorder; 62 men with Research Diagnostic Criteria alcoholism; and 62 healthy men screened to exclude any Axis I diagnosis or heavy alcohol use. The comorbid group matched the schizophrenia group on age and illness severity but was younger and drank 5 times less alcohol in their lifetimes than the alcoholism group. Gray and white matter volumes from 6 cortical regions were expressed as age- and head size-corrected z scores and were subjected to multivariate profile analyses.Gray matter volume deficits were present in all 3 patient groups but were greatest in the comorbid group. In the comorbid group, the most prominent volume deficits were in the prefrontal and anterior superior temporal regions.Despite lower alcohol exposure than in pure alcoholism, the comorbidity of schizophrenia with alcoholism has a particularly profound effect on prefrontal gray matter volume, compounding the prominent prefrontal deficits present independently in schizophrenia and alcoholism.
View details for Web of Science ID 000181572200004
View details for PubMedID 12622657
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Diffusion tensor imaging in normal aging and neuropsychiatric disorders
EUROPEAN JOURNAL OF RADIOLOGY
2003; 45 (3): 244-255
Abstract
The application of diffusion imaging to the quantitative study of the effects of normal aging and neuropsychiatric diseases on brain tissue microstructure has witnessed its greatest development just over the last few years. Measures derived from diffusion imaging have already been shown to have great utility in identifying age- and disease-related degradation of regional microstructure, particularly of white matter. Investigations comparing diagnoses hold promise for contribution to differential diagnosis. Correlations with cognitive and motor performance provide evidence for functional ramifications of these diffusion measures.
View details for Web of Science ID 000181482500010
View details for PubMedID 12595109
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How important are brain banks for alcohol research?
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2003; 27 (2): 310-323
Abstract
This article contains the proceedings of a symposium at the 2002 RSA/ISBRA Meeting in San Francisco, organized and chaired by Clive Harper and co-chaired by Izuru Matsumoto. The presentations were (1) Introduction, by Clive Harper; (2) The quality of tissue-a critical issue, by Therese Garrick; (3) The first systematic brain tissue donor program in Japan, by Izuru Matsumoto; (4) Brain scans after death-really! by Adolf Pfefferbaum, Elfar Adalsteinsson, and Edith Sullivan; (5) Capture that (genial) expression, by Joanne Lewohl and Peter Dodd; and (6) Neurochemical/pharmacological studies: experimental design and limitations, by Roger Butterworth.
View details for DOI 10.1097/01.ALC.0000052585.81056.CA
View details for Web of Science ID 000181172400018
View details for PubMedID 12605081
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Disruption of frontocerebellar circuitry and function in alcoholism
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2003; 27 (2): 301-309
Abstract
This article represents a symposium of the 2002 joint meeting of RSA and ISBRA held in San Francisco. Presentations were Neuropathology of alcohol-related cerebellar damage in humans, by Antony J. Harding; Neuropathological evidence of cerebellar damage in an animal model of alcoholism, by Roberta Pentney and Cynthia Dlugos; Understanding cortical-cerebellar circuits through neuroimaging study of chronic alcoholics, by Peter R. Martin and Mitchell H. Parks; and Functional reorganization of the brain in alcoholism: neuroimaging evidence, by John E. Desmond, S.H. Annabel Chen, Michelle R. Pryor, Eve De Rosa, Adolf Pfefferbaum, and Edith V. Sullivan.
View details for DOI 10.1097/01.ALC.0000052584.05305.98
View details for Web of Science ID 000181172400017
View details for PubMedID 12605080
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Using magnetic resonance imaging and diffusion tensor imaging to assess brain damage in alcoholics
ALCOHOL RESEARCH & HEALTH
2003; 27 (2): 146-152
Abstract
Brain imaging using conventional magnetic resonance imaging (MRI) has revealed that several brain structures in people with a history of chronic alcohol dependence are smaller in volume than the same brain structures in nonalcoholic control subjects. Areas that are particularly affected are the frontal lobes, which are involved in reasoning, judgment, and problem solving. Older people are especially vulnerable to the damaging effects of alcohol. It is unclear whether women show consistently more vulnerability to these changes in the brain than men do. In general, alcoholics evaluated before and after a period of abstinence show some recovery of tissue volume, whereas alcoholics evaluated again after continued drinking show further reductions in brain tissue volume. A new MR technique called diffusion tensor imaging (DTI) can aid in detecting the degradation of fibers (i.e., white matter) that carry information between brain cells (i.e., gray matter). With DTI, researchers studying alcoholics have been able to detect abnormalities in white matter not visible with conventional MRI. Ultimately DTI may be useful in elucidating the mechanisms that underlie macrostructural and functional brain changes seen with abstinence and relapse.
View details for Web of Science ID 000223800500004
View details for PubMedID 15303625
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Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study
PSYCHIATRY RESEARCH-NEUROIMAGING
2002; 116 (1-2): 43-52
Abstract
Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.
View details for Web of Science ID 000179601500004
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Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study. Magnetic resonance spectroscopy.
Psychiatry research
2002; 116 (1-2): 43-52
Abstract
Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.
View details for PubMedID 12426033
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Clinical signs of cerebellar dysfunction in schizophrenia, alcoholism, and their comorbidity
SCHIZOPHRENIA RESEARCH
2002; 57 (2-3): 281-291
Abstract
Abnormalities of cerebellar structure and function, long recognized as a hallmark of chronic alcohol abuse, have also occasionally been noted in patients with schizophrenia. We used a four-point rating scale to assess clinical signs of cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34) and alcohol dependence (N=15) as well as normal control subjects (N=28). Compared to controls, alcoholics had impaired ratings of gait ataxia and instability of stance with eyes closed, and schizophrenics had impaired ratings of stance with eyes closed. The incidence of dysdiadochokinesia was greater in schizophrenics, but not alcoholics, than controls. The incidence of gait and stance abnormalities was higher in both patient groups relative to controls: within the schizophrenic group, 50-70% of those with positive signs for gait or stance impairment were comorbid for alcoholism, while only 25% of those with positive signs for dysdiadochokinesia were comorbid for alcoholism. The presence of dysdiadochokinesia in the schizophrenic group suggests cerebellar dysfunction that is independent of the effects of alcohol. By contrast, clinical signs of cerebellar dysfunction of gait and stance in patients with schizophrenia may be secondary to the effects of alcohol on the cerebellum.
View details for Web of Science ID 000178358100018
View details for PubMedID 12223260
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The effects of alcoholism on auditory evoked potentials during sleep
JOURNAL OF SLEEP RESEARCH
2002; 11 (3): 247-253
Abstract
Normal aging is associated with a reduction in the probability that an auditory stimulus will evoke a K-complex during sleep. Additional concomitants of aging are a reduction in the amplitude of the K-complex-related N550, an augmentation of the P2 component and the appearance of a long-lasting positivity (LLP) in the auditory evoked potential. Normal aging is also associated with a dramatic reduction in slow wave sleep (SWS) and a reduction in the volume of cortical gray matter, particularly in the frontal and prefrontal regions of the brain. As in aging, alcoholism is associated with reductions in both cortical gray matter and SWS. It can, therefore, be hypothesized that alcoholics would show similar evoked potential changes to those seen in aging. To test this hypothesis, we studied seven middle-aged abstinent long-term alcoholics and eight age-matched normal controls. Each subject spent one night in the laboratory. Electroencephalogram (EEG) was recorded from six midline scalp sites and auditory stimuli were presented during stage 2 non-rapid eye movement sleep. N550 amplitude in the K-complex average was lower in the alcoholics as compared with controls as was the likelihood of K-complex production. No differences were noted in either amplitude or latency of the P2 or N350 components, and both groups displayed a prominent LLP potential. The pattern of reduced K-complex production and N550 amplitude in alcoholics as compared with age-matched controls is consistent with an hypothesized association between atrophy of the frontal lobes and reductions in SWS and K-complexes. The finding also suggests that the evoked K-complex may be a relatively simple measure of the effect of alcoholism on EEG during sleep.
View details for Web of Science ID 000177852300009
View details for PubMedID 12220321
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Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals
PSYCHIATRY RESEARCH
2002; 111 (1): 65-74
Abstract
Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others.
View details for Web of Science ID 000177511200008
View details for PubMedID 12140121
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Alcoholism and AIDS: Magnetic resonance imaging approaches for detecting interactive neuropathology
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2002; 26 (7): 1031-1046
Abstract
Both alcohol abuse and human immunodeficiency virus (HIV) infection have deleterious effects on brain structure, metabolism and function. In individuals with both afflictions these effects are doubtless additive and may interact to produce synergistic adverse effects. Further, the normal processes of aging produce brain degeneration that leaves older people especially vulnerable to the untoward effects of alcohol abuse and HIV infection. Advances in in vivo brain imaging now make practical the clinical study of the interaction of alcoholism and HIV infection and the potential of increased vulnerability produced by advancing age. In addition to structural magnetic resonance imaging (MRI), which provides quantitative assessments of brain macrostructure, are diffusion tensor imaging (DTI), which assesses microstructural integrity, magnetic resonance spectroscopy (MRS), which provides assessment of brain chemical moieties related to neuronal viability, and functional magnetic resonance imaging (fMRI), which provides assessment of localized blood oxygenation state association with performance of specific cognitive or motor tasks. Here, we first review postmortem observations on patients with HIV infection and with alcoholism to identify the cell types and brain regions most affected by the end stage of the disease. We then review in vivo neuroimaging studies of brain changes associated with HIV infection, chronic alcohol use, their interaction, and the potentiating effects of age. While there are many studies of people with either HIV infection or chronic alcohol use alone currently little has been published on the interactive effects of these variables, despite the high prevalence of overlap. We conclude with a consideration of the methodological issues such studies must address.
View details for DOI 10.1097/01.ALC.0000021146.01778.55
View details for Web of Science ID 000176989100013
View details for PubMedID 12170114
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Influences of chorion type on measurements of the corpus callosum in adult monozygotic male twins?
AMERICAN JOURNAL OF HUMAN BIOLOGY
2002; 14 (3): 338-346
Abstract
MRI imaging was used to estimate volumes of corpus callosum structure in 45 pairs of identical (monozygotic, MZ) twins from the National Heart, Lung, and Blood Institute (NHLBI) twin study. Age range of the study subjects was from 68-78 years. Finger, palm, and footprint data (dermatoglyphics) collected at previous examinations of the NHLBI twin study were available for 39 pairs. The dermatoglyphics were scored for an index to retrospectively assess chorion type in MZ twin-pairs. The results indicated an association between variability in various structures of the corpus callosum with some of these dermatoglyphic traits, suggesting greater structural variation within pairs with dichorionic placentas. In contrast, total intracranial volume, which has similar heritability estimates as a result of shared genetic effects with the corpus callosum, was unrelated to the dermatoglyphic traits. The results provide indirect evidence that the intrauterine environment may influence twin-pair similarity of corpus callosum measures in adults.
View details for DOI 10.1002/ajhb.10027
View details for Web of Science ID 000175224400006
View details for PubMedID 12001090
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Speed and efficiency but not accuracy or timing deficits of limb movements in alcoholic men and women
37th Annual Meeting of the American-College-of-Neuropsychopharmacology
BLACKWELL PUBLISHING. 2002: 705–13
Abstract
Lesions of the cerebellum, a concomitant of alcoholism, can disrupt quality and regularity of movement. Whether evidence for such dysfunction lingers in patients with uncomplicated alcoholism, which is known to affect cerebellar structural integrity, is controversial.We used quantitative measures to examine component processes of five classes of movement associated with regional cerebellar function: limb ataxia (alternated finger tapping and variants of the finger-to-nose and heel-to-shin tests), paced tapping, eye-hand coordinated tracing, timed response reflecting preparation and execution time, and postural stability. The subjects examined were 39 abstinent alcoholics (13 men and 26 women) and 21 age-matched controls (9 men and 12 women). For limb ataxia, the dependent measures were the trajectory deviation from the subject's own average movement path and the speed of travel from beginning points to endpoints.Repeated-measures analysis of variance comparing movement speed of finger to nose and heel to shin yielded significant interactions in all conditions (p < 0.007); this indicated that the alcoholics were relatively slower in the upper- than lower-limb tasks. Movements by the alcoholic men were significantly slower but less deviant from an ideal trajectory in all upper-limb conditions than those of the control men (p < 0.002). Although measures of lower-limb movement trajectory did not distinguish the groups, tests of ataxia of stance and gait did. The groups did not differ, however, on tests of timed tapping or sinusoid tracing.Alcohol-related postural instability in abstinent alcoholics is functional evidence supporting the postulated damage to the anterior superior vermis. Altered speed or accuracy trade-offs, with alcoholics moving slower to attain equivalent or even smaller trajectory deviations, are symptomatic of cerebellar hemisphere dysfunction that is characterized by deliberation of otherwise automatic movements.
View details for Web of Science ID 000175643900016
View details for PubMedID 12045480
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Evoked K-complex production during stage 2 sleep in recovering long-term alcoholics
AMER ACAD SLEEP MEDICINE. 2002: A439–A440
View details for Web of Science ID 000174927200622
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Differential rates of regional brain change in callosal and ventricular size: a 4-year longitudinal MRI study of elderly men
CEREBRAL CORTEX
2002; 12 (4): 438-445
Abstract
Brain structure changes in size with normal aging, but the rate at which different structures change is controversial. We used magnetic resonance imaging (MRI) performed twice, 4 years apart, to compare rates of age-related size change of the corpus callosum, which has been inconsistently observed to thin with age, with change in the lateral ventricles, which are well established to enlarge. Subjects were 215 community dwelling, elderly men (70-82 years old at initial MRI), who were participants in a longitudinal study of cardiovascular risk factors. Percent change in size was significant for both the callosal and ventricular measures, but annual rate of ventricular expansion (2.9%) was significantly greater than annual rate of callosal thinning (-0.9%). Callosal regions showed statistically equivalent rates of shrinkage; ventricular dilatation was symmetrical. Neither callosal and ventricular rates of change correlated with each other (r = 0.01), nor did genu and splenium rates of change correlate with each other (r = 0.05). Tests of speeded processing were administered contemporaneously with both MRIs to examine functional ramifications of observed brain changes. Decline in the Mini-Mental State Examination was related to thinning of the splenium, and decline in Stroop test word reading was selectively related to thinning of the callosal body. These longitudinal data support the contentions that differential rates of change occur in different brain regions in normal aging, age-related callosal thinning contributes to functional declines, and rate of change in one region can be independent of rate of change in another region, even within a brain structure.
View details for Web of Science ID 000174370200010
View details for PubMedID 11884358
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Basal forebrain nuclei activation during acquisition of a proactive interference simultaneous discrimination task in healthy and nonamnesic alcoholic men: An fMRI study
MIT PRESS. 2002: 162–163
View details for Web of Science ID 000174072000675
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Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism
NEUROIMAGE
2002; 15 (3): 708-718
Abstract
The results of in vivo neuroimaging studies assessing whether and where brain white matter damage occurs in alcoholic women is controversial. To address this controversy, we examined regional white matter macrostructure and microstructure, the latter of which may be more sensitive to the detection of subtle fiber disruption than gross measures of size. Accordingly, we used conventional magnetic resonance imaging (MRI) to quantify regional callosal size and diffusion tensor imaging (DTI) to examine intravoxel coherence (fractional anisotropy, FA) and intervoxel coherence (C) of white matter of the genu and splenium of the corpus callosum and of the centrum semiovale in 12 detoxified alcoholic women and 18 control women. Additional analyses examined sex differences in FA and C in alcoholic women compared with alcoholic men. Despite absence of group differences in regional areas of callosal macrostructure, the alcoholic women had lower FA and C in genu and centrum semiovale than the control group of women. These measures also correlated with total lifetime consumption of alcohol and performance on a test of visual search in the alcoholic women. Sex comparisons revealed similar extents of FA abnormality in the genu and centrum semiovale in alcoholic men and women and differential effects in other DTI measures, with abnormalities present in splenium FA and C in the men and abnormalities present in centrum C in the women. These results provide in vivo evidence for disruption of white matter microstructure in alcoholic women not necessarily detectable with coarser measures of white matter mass and perhaps antedating its appearance.
View details for DOI 10.1006/nimg.2001.1018
View details for Web of Science ID 000174163900025
View details for PubMedID 11848714
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Corpus callosum, pons, and cortical white matter in alcoholic women
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2002; 26 (3): 400-406
Abstract
To measure the effect of alcohol abuse on white matter brain macrostructure in women with alcoholism and to determine whether observed abnormalities interact with age.Quantitative measures of corpus callosum area, cortical white matter volume, and pons volume were derived from magnetic resonance imaging scans obtained from 34 women with DSM-III-R alcoholism (aged 28-64, mean 41 years) and 35 healthy women (aged 22-65, mean 42 years). Transverse relaxation time of the pons was also obtained.No significant group differences in any brain measures were observed. However, in alcoholics greater length of sobriety was associated with more cortical white matter, and higher lifetime levels of alcohol consumption were associated with smaller volumes and prolonged transverse relaxation time in the pons.Despite a lack of overall deficits in white matter macrostructural size in alcoholic women, certain white matter structures showed alcohol exposure vulnerability whereas others showed evidence of recovery with abstinence.
View details for Web of Science ID 000174612800015
View details for PubMedID 11923595
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A profile of neuropsychological deficits in alcoholic women
20th Annual Meeting of the Research-Society-on-Alcoholism
AMER PSYCHOLOGICAL ASSOC. 2002: 74–83
Abstract
Neuropsychological deficits, most notable in executive, visuospatial, and functions of gait and balance, are detectable in alcoholic men even after a month of sobriety. Less well established are the severity and profile of persisting deficits in alcoholic women. The authors used an extensive test battery to examine cognitive and motor functions in 43 alcoholic women who were sober, on average, for 3.6 months. Functions most severely affected in alcoholic women involved visuospatial and verbal and nonverbal working memory processes as well as gait and balance. Areas of relative sparing were executive functions, declarative memory, and upper-limb strength and speed. The authors found that lifetime alcohol consumption was related to impairment severity on Block Design (Wechsler Adult Intelligence Scale-Revised, D. Wechsler, 1981) and verbal and nonverbal working memory, suggesting a dose effect of alcohol abuse. The alcohol-related deficits in working memory, visuospatial, and balance implicate disruption of prefrontal, superior parietal, and cerebellar brain systems.
View details for DOI 10.1037//0894-4105.16.1.74
View details for Web of Science ID 000173794700009
View details for PubMedID 11853359
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N-acetylaspartate - A marker of neuronal integrity
ANNALS OF NEUROLOGY
2001; 50 (6): 823-823
View details for Web of Science ID 000172410900022
View details for PubMedID 11761485
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Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis
PSYCHIATRY RESEARCH-NEUROIMAGING
2001; 108 (1): 1-15
Abstract
Chronic interictal psychotic syndromes, often resembling schizophrenia, develop in some patients with epilepsy. Although widespread brain abnormalities are recognized as characteristic of schizophrenia, prevailing but controversial hypotheses on the co-occurrence of epilepsy and psychosis implicate left temporal lobe pathology. In this study, quantitative MRI methods were used to address the regional specificity of structural brain abnormalities in patients with epilepsy plus chronic interictal psychosis (E+PSY, n=9) relative to three comparison groups: unilateral temporal lobe epilepsy without chronic psychosis (TLE, n=18), schizophrenia (SCZ, n=46), and healthy control subjects (HC, n=57). Brain measures, derived from a coronal spin-echo MRI sequence, were adjusted for age and cerebral volume. Relative to HC, all patient groups had ventricular enlargement and smaller temporal lobe, frontoparietal, and superior temporal gyrus gray matter volumes, with the extent of these abnormalities greatest in E+PSY. Only TLE had temporal lobe white matter deficits, as well as smaller hippocampi, which were ipsilateral to the seizure focus. Structural brain abnormalities in E+PSY are not restricted to the left temporal lobe. The confluence of cortical gray matter deficits in E+PSY and SCZ suggests salience to chronic psychosis.
View details for Web of Science ID 000172053800001
View details for PubMedID 11677063
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Magnetic resonance relaxometry reveals central pontine abnormalities in clinically asymptomatic alcoholic men
39th Annual Meeting of the American-College-of-Neuropsychopharmacology
BLACKWELL PUBLISHING. 2001: 1206–12
Abstract
Central pontine myelinolysis (CPM) is a rare, debilitating, life-threatening condition, associated with chronic alcoholism, rapid correction of hyponatremia, and advanced age. It is unknown, however, whether older alcoholic patients who by age and diagnosis are at risk for CPM have objectively determined neuroimaging evidence of preclinical CPM that could be valuable in understanding its development and in initiating appropriate treatment. Accordingly, we examined central pontine magnetic resonance (MR) transverse relaxation time (T2), which reflects myelin and axonal integrity when measured in white matter and is prolonged with pathology that causes increased free water content in tissue.The subjects were 46 alcoholic men who were abstinent from alcohol for about 1 month and were asymptomatic for CPM, 9 men and 1 woman with alcoholic Korsakoff's syndrome (KS), and 74 healthy control men. All subjects received coronally acquired dual-echo MR imaging (MRI), from which T2 times were calculated in central pons. MRI films were read clinically and independently of relaxometry results. Hematological and neuropsychological data were also available for many subjects.Only the KS group showed prolonged T2 times; however, pontine T2 prolongation increased significantly with older age in the asymptomatic alcoholics but not controls. Clinical radiological readings detected pontine signal hyperintensity in five KS subjects (two without dementia and three with dementia), one control, and no alcoholic patient. Hematologic indexes of macrocytic anemia and nutritional deficiency and neuropsychological measures of verbal and nonverbal fluency correlated with prolonged T2 times in alcoholic men.This CPM-like condition, manifest as prolonged T2, may occur with higher incidence than previously thought in clinically asymptomatic alcoholism and may contribute to neuropsychological compromise of initiation and production. Preclinical detection of abnormal pontine signal properties with MR relaxometry may identify patients at high risk for developing CPM.
View details for Web of Science ID 000170458200017
View details for PubMedID 11505052
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Sex differences in corpus callosum size: relationship to age and intracranial size
27th Annual Meeting of the International-Neuropsychological-Society
ELSEVIER SCIENCE INC. 2001: 603–11
Abstract
This quantitative MRI study reports measurement of corpus callosum area taken from midsagittal brain images in 51 healthy men and 41 healthy women, spanning the adult age range (22 to 71 years). Men had larger brains and corpora callosa than women, but callosal size did not correlate with age in either sex. Intracranial (i.c.) volume (ICV) and midsagittal i.c. area (ICA) of brain were used in covariate, regression, and ratio analyses to determine whether sex differences in the corpus callosum endured with statistical adjustment for sex differences in maximally attained brain size. With the exception of one ratio measure, the different statistical adjustments for the contribution of sex differences in brain size to corpus callosum size all indicated that men had larger corpora callosa than women for their brain size. A subsample of men and women selected to be matched on i.c. volume and age confirmed this statistical observation. Sexual dimorphism in the corpus callosum is not a simple artifact of sex differences in brain size and may reflect differences in connectivity necessitated by differences in brain size.
View details for Web of Science ID 000169912200011
View details for PubMedID 11445261
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Motor sequencing deficits in schizophrenia: A comparison with Parkinson's disease
International Congress on Schizophrenia
AMER PSYCHOLOGICAL ASSOC. 2001: 342–50
Abstract
Motor abnormalities occur in schizophrenia (SZ) and may arise from striatal dysfunction. This study examined whether the pattern of performance on simple and complex motor abilities in SZ was similar to that of patients with Parkinson's disease (PD). Quantitative tests of speeded movement and motor and cognitive sequencing were used to assess 25 SZ, 16 PD, and 84 normal controls (NCs). Sequencing performance was also examined with motor rigidity taken into account. Compared with the NC group, the SZ and PD groups were impaired on measures of motor rigidity and motor sequencing. With rigidity accounted for, the SZ group was significantly more impaired than the PD group on motor sequencing; cognitive and motor processes contributed to the motor deficit. Cognitive sequencing performance predicted motor sequencing performance in PD but not SZ. Although both SZ and PD resulted in significant motor and cognitive sequencing deficits, the pattern and correlates of these deficits differ, suggesting that the affected neural systems underlying motor deficits in SZ are different from those involved in PD.
View details for DOI 10.1037//0894-4105.15.3.342
View details for Web of Science ID 000170947000003
View details for PubMedID 11499989
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Reorganization of frontal systems used by alcoholics for spatial working memory: An fMRI study
NEUROIMAGE
2001; 14 (1): 7-20
Abstract
Chronic alcoholism is associated with impairment in sustained attention and visual working memory. Thus, alcoholics have reduced ability, but not necessarily inability, to perform these executive tasks, assumed to be subserved by regions of prefrontal cortex. To identify neural substrates associated with this impairment, we used functional MRI (fMRI) to determine whether alcoholics invoke the same or different brain systems as controls when engaged in working memory tasks that the two groups were able to perform at equivalent levels. The fMRI spatial working memory paradigm instructed subjects to respond with a button press when a target position was either in the center of the field (match to center) or matched the spatial position of one presented two items previously (match 2-back) or to rest. Using whole-brain fMRI, alcoholics showed diminished activation frontal cortical systems compared to controls (bilateral dorsolateral prefrontal cortex) when responding 2-back vs rest. In the center vs rest contrast, the control group compared with the alcoholic group activated a large expanse of prefrontal cortex (including Brodmann areas 9, 10, and 45), whereas there was significantly greater activation by the alcoholic group relative to the control group localized more posteriorly and inferiorly in the frontal cortex (area 47). Examination of within group activation patterns revealed two different patterns of activation: the control group exhibited activation of the dorsal ("Where?") stream for visual spatial working memory processing, whereas the alcoholic group exhibited activation of the ventral ("What?") stream and declarative memory systems to accomplish the spatial working memory task. The differences in the pattern of brain activations exhibited by the alcoholic and control groups, despite equivalence in behavioral performance, is consistent with a functional reorganization of the brain systems invoked by alcoholic individuals or invocation of an inappropriate brain system when engaged in a visual spatial task requiring working memory.
View details for Web of Science ID 000169498000002
View details for PubMedID 11525339
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Genetic regulation of regional microstructure of the corpus callosum in late life
NEUROREPORT
2001; 12 (8): 1677-1681
Abstract
In order to identify brain structural phenotypes that remain under significant genetic control in late adulthood, we examined the heritability of corpus callosum macrostructure (i.e. size) using MRI and microstructure (e.g. myelin) using diffusion tensor imaging in 15 monozygotic and 18 dizygotic twin pairs of elderly men. The relative proportion of genetic to environmental influences varied considerably by region and structural type and was 5:1 for callosal macrostructure, 3:1 for splenium microstructure, and 1:1 for genu microstructure. This is the first in vivo identification of quantifiable phenotypes of brain white matter microstructure and demonstrates significant and differential genetic regulation in old age, with anterior interhemispheric connecting pathways more susceptible than posterior pathways to environmental influences.
View details for Web of Science ID 000169185400028
View details for PubMedID 11409738
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N1 and P300 abnormalities in patients with schizophrenia epilepsy, and epilepsy with schizophrenialike features
55th Annual Meeting of the Society-of-Biological-Psychiatry
ELSEVIER SCIENCE INC. 2001: 848–60
Abstract
The scalp-recorded N1 and P300 components of the event-related brain potential (ERP) are commonly reduced in patients with schizophrenia but not in patients with epilepsy. Epilepsy patients with interictal chronic schizophrenialike features (EPI-SZ) provide a comparison group for determining whether the ERP amplitude abnormalities seen in schizophrenic patients are associated with shared clinical features of EPI-SZ and schizophrenic patients or overlapping pathophysiologies, or are specific to a distinct schizophrenia etiology.Patients with schizophrenia (n = 24) were compared with normal control subjects (n = 32) and patients with epilepsy syndromes on visual and auditory oddball ERP paradigms. Epilepsy patients included those with chronic interictal schizophrenialike features (n = 6) and those without (n = 16).Auditory P300 amplitude was reduced in both schizophrenic and EPI-SZ patients, whose positive or negative symptoms did not differ. In contrast, N1 amplitude was reduced only in schizophrenic patients. Delays in both N1 and P300 were associated with epilepsy patients and EPI-SZ but not schizophrenic patients.The schizophrenialike symptoms in epilepsy probably represent a phenocopy of schizophrenia with common clinical features and some common pathophysiologies but distinct etiologies. P300 amplitude appears to be sensitive to schizophrenialike features, regardless of whether they occur in the context of schizophrenia or epilepsy. N1 amplitude reduction appears to be specific to schizophrenia, suggesting its sensitivity to the distinct etiology of schizophrenia.
View details for Web of Science ID 000168559100004
View details for PubMedID 11343681
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Neuroimaging in alcoholism: Ethanol and brain damage
35th Annual Meeting of the Japanese-Medical-Society-of-Alcohol-and-Drug-Studies/10th International-Society-for-Biomedical-Research-on-Alcoholism
WILEY-BLACKWELL. 2001: 104S–109S
Abstract
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The co-chairs were Karl Mann and Ingrid Agartz. The presentations were (1) Neuropathological changes in alcohol-related brain damage, by Clive Harper; (2) Regional brain volumes including the hippocampus and monoamine metabolites in alcohol dependence, by Ingrid Agartz, Susan Shoaf, Robert R, Rawlings, Reza Momenan, and Daniel W Hommer; (3) Diffusion tensor abnormalities in imaging of white matter alcoholism, by Adolf Pfefferbaum and Edith V. Sullivan; (4) Use of functional MRI to evaluate brain activity during alcohol cue exposure in alcoholics: Relationship to craving, by Raymond F. Anton, David J. Drobes, and Mark S. George; and (5) mu-Opiate receptor availability in alcoholism: First results from a positron emission tomography study, by Karl Mann, Roland Bares, Hans-Juergen Machulla, Goetz Mundle, Matthias Reimold, and Andreas Heinz.
View details for Web of Science ID 000168846000019
View details for PubMedID 11391058
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Pontine but not thalamic volume deficits in schizophrenia when comorbid for alcoholism
ELSEVIER SCIENCE BV. 2001: 167–68
View details for Web of Science ID 000168411700566
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Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia
AMERICAN JOURNAL OF PSYCHIATRY
2001; 158 (4): 646-649
Abstract
This study was an examination of basal ganglia dysfunction in schizophrenia using functional magnetic resonance imaging (fMRI).The authors used a motor sequencing task to investigate activation of the caudate, anterior putamen plus globus pallidus, and posterior putamen plus globus pallidus in eight subjects with schizophrenia and 12 group-matched comparison subjects. Differences in activation of the thalamus, the target of direct output from the globus pallidus, were also examined.The schizophrenia subjects showed significant bilateral deficits in the posterior putamen, globus pallidus, and thalamus but not the anterior putamen plus globus pallidus or caudate. Functional connectivity analysis revealed that the deficits in thalamic activation were related to deficits in posterior putamen and globus pallidus activation.These results provide fMRI evidence for basal ganglia dysfunction in subjects with schizophrenia and suggest that this deficit results in disrupted outflow to the thalamus. These deficits may underlie the behavioral impairments in goal-directed action observed in schizophrenia.
View details for Web of Science ID 000167931900023
View details for PubMedID 11282705
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Remote memory for public figures in Alzheimer's disease: Relationships to regional cortical and limbic brain volumes
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
2001; 7 (3): 384-390
Abstract
This study examined the relationships between regional cortical and hippocampal brain volumes and components of remote memory (recall, recognition, sequencing, and photo naming of presidential candidates) in 13 individuals with Alzheimer's disease (AD). Recognition and sequencing of remote memory for public figures were associated with regional cortical volumes. Specifically, lower recognition and sequencing scores were associated with smaller parietal-occipital cortical volumes; poorer sequencing was also associated with smaller prefrontal cortical volumes. By contrast, poorer anterograde but not remote memory scores were correlated with smaller hippocampal volumes. Within the constraints of the brain regions measured, these findings highlight the importance of the posterior cortical areas for selective remote memory processes and provide support for the dissociation between cortically mediated remote memory and hippocampally mediated anterograde memory.
View details for Web of Science ID 000168425100012
View details for PubMedID 11311039
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Longitudinal decline of the neuronal marker NAA in Alzheimer's disease as measured by 1H magnetic resonance spectroscopic imaging
ELSEVIER SCIENCE INC. 2001: 332–32
View details for Web of Science ID 000167154800024
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Functional neuroanatomy of auditory working memory in schizophrenia: Relation to positive and negative symptoms
NEUROIMAGE
2001; 13 (3): 433-446
Abstract
Functional brain imaging studies of working memory (WM) in schizophrenia have yielded inconsistent results regarding deficits in the dorsolateral prefrontal (DLPFC) and parietal cortices. In spite of its potential importance in schizophrenia, there have been few investigations of WM deficits using auditory stimuli and no functional imaging studies have attempted to relate brain activation during auditory WM to positive and negative symptoms of schizophrenia. We used a two-back auditory WM paradigm in a functional MRI study of men with schizophrenia (N = 11) and controls (N = 13). Region of interest analysis was used to investigate group differences in activation as well as correlations with symptom scores from the Brief Psychiatric Rating Scale. Patients with schizophrenia performed significantly worse and were slower than control subjects in the WM task. Patients also showed decreased lateralization of activation and significant WM related activation deficits in the left and right DLPFC, frontal operculum, inferior parietal, and superior parietal cortex but not in the anterior cingulate or superior temporal gyrus. These results indicate that in addition to the prefrontal cortex, parietal cortex function is also disrupted during WM in schizophrenia. Withdrawal-retardation symptom scores were inversely correlated with frontal operculum activation. Thinking disturbance symptom scores were inversely correlated with right DLPFC activation. Our findings suggest an association between thinking disturbance symptoms, particularly unusual thought content, and disrupted WM processing in schizophrenia.
View details for DOI 10.1006/nimg.2000.0699
View details for Web of Science ID 000167154300005
View details for PubMedID 11170809
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Progressive brain volume changes and the clinical course of schizophrenia in men - A longitudinal magnetic resonance imaging study
55th Annual Meeting of the Society-of-Biological-Psychiatry
AMER MEDICAL ASSOC. 2001: 148–57
Abstract
We sought to determine whether the brain dysmorphology previously observed cross-sectionally in people with schizophrenia progresses over time and whether such progression is related to the severity of the illness course.Men with chronic schizophrenia (n = 24) and control men (n = 25) received 2 brain magnetic resonance imaging scans, on average 4 years apart. Changes in brain volume were adjusted for head-repositioning error and expressed as slopes (cubic centimeters per year). Clinical course severity for the schizophrenic patients was assessed using the mean of time 1 and time 2 Brief Psychiatric Rating Scale (BPRS) scores and the percentage of time the patient was hospitalized during the interscan interval.Schizophrenic patients exhibited faster volume decline than control subjects in right frontal gray matter and bilateral posterior superior temporal gray matter, as well as faster cerebrospinal fluid volume expansion in right frontal sulci, left lateral ventricle, and bilateral prefrontal and posterior superior temporal sulci. Faster rates of frontal sulcal expansion were related to greater BPRS total and positive symptom scores and longer time hospitalized. Prefrontal gray matter decline and sulcal expansion were associated with greater BPRS negative symptom scores and longer time hospitalized. Temporal lobe gray matter decline was associated with greater BPRS total and negative symptom scores.This controlled study revealed that patients with chronic schizophrenia exhibited accelerated frontotemporal cortical gray matter decline and cortical sulcal and lateral ventricular expansion. Further, greater clinical severity was associated with faster rates of frontotemporal brain volume changes. These observations are consistent with a progressive pathophysiological process but need to be replicated in a larger sample.
View details for Web of Science ID 000166842600005
View details for PubMedID 11177116
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Sex differences in the effects of alcohol on brain structure
Annual Meeting of the Research-Society-of-Alcoholism
AMER PSYCHIATRIC PUBLISHING, INC. 2001: 188–97
Abstract
This study investigated whether alcoholic women manifest deficits in cortical gray and white matter volumes and ventricular enlargement similar to those seen in alcoholic men.Volumetric measures of intracranium, cortical gray matter, white matter and sulci, and lateral and third ventricles were obtained from magnetic resonance images of 42 women and 44 men with DSM-III-R alcoholism and age-matched healthy comparison groups (37 women and 48 men). Groups of alcoholic men and women were matched on age and length of sobriety, but men had a 2.5 times higher lifetime alcohol consumption than women.Women, regardless of diagnosis, had less cortical gray and white matter and smaller third ventricles than men, consistent with sex-related differences in intracranial volume. Alcoholics had larger volumes of cortical sulci and lateral and third ventricles than comparison subjects. Diagnosis-by-sex interactions for cortical white matter and sulcal volumes were due to abnormalities in alcoholic men but not alcoholic women, relative to same-sex comparison subjects. This interaction persisted for cortical sulci after covarying for lifetime alcohol consumption. Slopes relating cortical gray matter and sulcal volumes to age were steeper in alcoholic than in comparison men. Slopes relating lateral ventricle volume to age were steeper in alcoholic than in comparison women. In alcoholic women, longer sobriety was associated with larger white matter volumes.Alcoholic men and women show different brain morphological deficits, relative to same-sex comparison subjects. However, age and alcoholism interact in both sexes, which puts all older alcoholics at particular risk for the negative sequelae of alcoholism.
View details for Web of Science ID 000166761400007
View details for PubMedID 11156800
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Equivalent disruption of regional white matter microstructure in ageing healthy men and women
NEUROREPORT
2001; 12 (1): 99-104
Abstract
Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.
View details for Web of Science ID 000166411900022
View details for PubMedID 11201100
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Heritability of hippocampal size in elderly twin men: Equivalent influence from genes and environment
HIPPOCAMPUS
2001; 11 (6): 754-762
Abstract
Recent studies have established that environmental factors can modify hippocampal structure and enhance function in adult rodents, but the extent to which genes and the environment exert differential contributions to hippocampal structural integrity in humans is unknown. Here, we applied the twin model in a large sample of elderly twin men to examine in late life the balance of environmental and genetic effects on the size of the hippocampus in comparison with other brain structures. This study provides novel evidence that the volume of the hippocampus, as measured on MRI, is subject to substantially less genetic control than are comparison brain regions also measured: temporal horn volume, midsagittal area of the corpus callosum, and intracranial volume (ICV). In particular, about 60% of the temporal horn variance and 80% of the callosal and ICV variance was attributable to genetic influences, whereas only 40% of the hippocampal variance was attributable to genetic influences. These results suggest that environment, whether by itself or in interaction with genes, has the potential of exerting greater and possibly longer control in modifying hippocampal size than other brain regions that are under greater genetic control. Considering the potential of environmental modification of this structure suggested by lower heritability, the hippocampus appears well-suited to support the dynamic processes of encoding and consolidation of new, declarataive memories.
View details for Web of Science ID 000172988800016
View details for PubMedID 11811670
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Basal ganglia involvement in memory-guided movement sequencing
NEUROREPORT
2000; 11 (16): 3641-3645
Abstract
The basal ganglia (BG) are thought to play a critical role in motor planning and movement sequencing. While electrophysiological and imaging studies have shown that the dorso-lateral prefrontal cortex (DLPFC) is involved in working memory (WM), the involvement of the BG in this process is not well understood. We used a motor sequencing task to investigate the differential role of BG nuclei in memory-guided movement. Significant activation was observed in the DLPFC and posterior putamen and globus pallidus (GP), with a trend in the caudate and no differences in the anterior putamen. We then investigated the effect of BG outflow on thalamic activation using functional connectivity analysis. Activation in the posterior putamen + GP was found to be correlated with thalamic activation only in the hemisphere contralateral to movement. These results provide the first fMRI evidence that the BG may modulate activity in the thalamus during working memory-guided movement sequencing. Our findings suggest that the BG activation may reflect increased motor sequencing demands during the memory-guided movement condition and, specifically, that the posterior putamen and GP may play a role in maintenance of representations in WM in a manner that contributes to planning and temporal organization of motor sequencing.
View details for Web of Science ID 000165301600048
View details for PubMedID 11095535
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Left temporal deficit of P300 in patients with schizophrenia: effects of task
INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
2000; 38 (1): 71-79
Abstract
P300 is often, but not always, observed to be more reduced over left than right temporal lobes in patients with schizophrenia. The possibility that task differences contribute to the inconsistency in the literature was explored in this study. ERPs were collected from 17 right-handed men with schizophrenia (DSM-IIIR) and 11 right-handed healthy male community controls, performing three auditory oddball tasks - respond to a target tone by: (1) counting; (2) pressing a response button with the right index finger; or (3) pressing a response button with the left index finger. Although patients with schizophrenia had smaller and later P300 amplitudes than controls, they did not have smaller P300s over the left temporal scalp (T3) than over the right (T4). P300 recorded over the left (C3) and right (C4) motor cortices indicated sensitivity to responding hand, with greater negativity being associated with contralateral button pressing. Failure to find P300 asymmetry is not related to the presence or absence of a button pressing task, or the hand used for button pressing. Rather, P300 asymmetry may be related to structural neuroanatomical asymmetries.
View details for Web of Science ID 000090143800006
View details for PubMedID 11027795
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Contribution of alcohol abuse to cerebellar volume deficits in men with schizophrenia
ARCHIVES OF GENERAL PSYCHIATRY
2000; 57 (9): 894-902
Abstract
It is controversial whether cerebellar tissue volume deficits occur in schizophrenia and, if so, what regions and tissue types are affected. Complicating such investigations is the high incidence of alcoholism comorbidity in patients with schizophrenia that itself can contribute to cerebellar abnormalities.We studied 61 healthy men (control subjects), 25 men with alcoholism, 27 men with schizophrenia, and 19 men comorbid for schizophrenia and alcoholism with the use of magnetic resonance imaging. Cerebellar structures were outlined manually, tissue classification was determined statistically, and regional volumes were corrected for normal variation in head size and age.Patients with schizophrenia alone had enlarged fourth ventricles (1.5 SD relative to controls) but showed no cerebellar tissue volume deficits. The alcoholic group had gray and white matter vermian deficits (-0.5 SD), most prominent in anterior superior lobules, and gray matter hemisphere deficits (-0.8 SD), but not fourth ventricle enlargement. The comorbid group had cerebellar hemisphere (-1.3 SD) and vermian gray matter volume deficits (-0.7 SD) and fourth ventricular enlargement (1.6 SD); these abnormalities were greater than in either single-diagnosis group, despite significantly lower levels of alcohol consumption compared with the alcoholic group. Gray matter volume in the anterior superior vermis correlated with lifetime alcohol consumption in the schizophrenic and comorbid groups when combined.Cerebellar tissue volume deficits were detected in schizophrenia only when accompanied by alcoholism. By contrast, fourth ventricular enlargement occurred in schizophrenia even without alcoholism, although it was exacerbated by alcoholism. These findings support a model of cerebellar supersensitivity to alcohol-related tissue volume deficits in schizophrenia.
View details for Web of Science ID 000089179500011
View details for PubMedID 10986553
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In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2000; 24 (8): 1214-1221
Abstract
Postmortem studies report degradation of brain white matter microstructure in chronic alcoholism, but until recently, in vivo neuroimaging could provide measurement only at a macrostructural level. The development of magnetic resonance diffusion tensor imaging (DTI) for clinical use offers a method for depicting and quantifying the diffusion properties of white matter expressed as intravoxel and intervoxel coherence of tracts and fibers.This study used DTI to examine the intravoxel coherence measured as fractional anisotropy (FA) and intervoxel coherence (C) of white matter tracts of the genu and splenium of the corpus callosum and of the centrum semiovale in 15 detoxified alcoholic men and 31 nonalcoholic control subjects. Exploratory correlational analyses examined the relationships between regional DTI measures and tests of attention and working memory in the alcoholic patients.The alcoholic group had lower regional FA than the control group. C was lower in the alcoholics than controls in the splenium only. Working memory correlated positively with splenium FA, whereas attention correlated positively with genu C.These results provide in vivo evidence for disruption of white matter microstructure in alcoholism and suggest that interruption of white matter fiber coherence contributes to disturbance in attention and working memory in chronic alcoholism.
View details for Web of Science ID 000088831600012
View details for PubMedID 10968660
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Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging
MAGNETIC RESONANCE IN MEDICINE
2000; 44 (2): 259-268
Abstract
Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of the orientation and coherence of brain white matter tracts but suffers from field inhomogeneity-induced geometric distortion. To reduce spatial distortion, polynomial warping corrections were applied and the effects tested on measures of fractional anisotropy (FA) in the genu and splenium of corpus callosum. Implementation entailed spatially warping EP images obtained without diffusion weighting (b = 0) to long-echo T(2)-weighted fast spin echo images, collected for anatomical delineation, tissue segmentation, and coregistration with the diffusion images. Using the optimal warping procedure (third-order polynomial), the effects of age on FA and a quantitative measure of intervoxel coherence (C) in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal white matter were examined in 31 healthy men (23-76 years). FA declined significantly with age in all regions except the splenium, whereas intervoxel coherence positively correlated with age in the genu. Magn Reson Med 44:259-268, 2000.
View details for Web of Science ID 000088545600013
View details for PubMedID 10918325
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Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: Relation to ataxia
6th International Congress on Schizophrenia Research
AMER PSYCHOLOGICAL ASSOC. 2000: 341–52
Abstract
The authors used magnetic resonance imaging to measure gray and white matter volumes in cerebellar hemispheres and 4 vermian regions in 61 normal control (NC) men aged 23-72 years, 25 men with uncomplicated alcoholism (ALC), and 8 men and 1 woman with alcoholic Korsakoff s syndrome (KS). NC and ALC took quantitative gait and balance tests. Gray but not white matter volume declined with normal age in both hemispheres and anterior-superior vermis. ALC had gray but not white matter cerebellar hemisphere volume deficits, whereas KS had deficits in both tissue types. ALC and KS had gray and white matter volume deficits in anterior superior but not posterior inferior vermis. ALC had a 1 SD ataxia deficit, significantly and selectively correlated with white matter volume in anterior superior vermis. Regional distribution but not severity of cerebellar volume deficits is similar in alcoholic individuals whether or not complicated by KS and relates to ataxia.
View details for Web of Science ID 000088253400002
View details for PubMedID 10928737
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Segregation analysis of drinking problem in elderly men and their first-degree relatives from the Western Collaborative Group Study
ANNALS OF EPIDEMIOLOGY
2000; 10 (5): 309-315
Abstract
The purpose of this study is to determine the mode of inheritance of alcohol-related drinking problems.Family history was collected by interview from 493 elderly male participants (probands) in a follow-up cardiovascular exam of healthy white men living in the San Francisco Bay Area and Los Angeles. Segregation analysis was used to test for the presence of a major gene effect underlying the liability to develop an alcohol-related drinking problem.The results showed that the liability to drinking problem is due, in part, to a single major gene with no residual effects from shared familial influences.These results suggest that at least one major gene is involved in the genetic predisposition to develop drinking problem in late adulthood.
View details for Web of Science ID 000088620900007
View details for PubMedID 10942879
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Optimal voxel size for measuring global gray and white matter proton metabolite concentrations using chemical shift imaging
MAGNETIC RESONANCE IN MEDICINE
2000; 44 (1): 10-18
Abstract
Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations compared to single voxel methods. In the present study, the optimal voxel size is calculated from segmented human brain data and accompanying field maps. The optimal voxel size is found to be approximately 8 cc, but a wide range of values, 4-64 cc, can be chosen with little increase in estimated concentration error (<15%). Magn Reson Med 44:10-18, 2000.
View details for Web of Science ID 000087917000003
View details for PubMedID 10893515
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Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease
LANCET
2000; 355 (9216): 1696-1697
Abstract
In patients with Alzheimer's disease, but not in health controls, longitudinal magnetic resonance spectroscopy shows a striking decline in the neuronal marker, N-acetyl aspartate, despite little decline in underlying grey-matter volume.
View details for Web of Science ID 000086983800017
View details for PubMedID 10905250
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Pattern of motor and cognitive deficits in detoxified alcoholic men
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2000; 24 (5): 611-621
Abstract
Chronic excessive consumption of alcohol produces marked deficits in cognitive and motor abilities, although not all functions are affected to the same extent. Furthermore, although the occurrence of neuropsychological deficits in recently detoxified alcoholics is firmly established, the relative severity of these deficits, the specific neural systems that underlie the deficits, and their relationship to age and alcohol consumption variables either are less established or have proven elusive altogether.We administered an extensive battery of neuropsychological tests, chosen for their known sensitivity to brain lesions in specific locations, to 71 recently (1 month) detoxified alcoholic men and 74 healthy controls who spanned the adult age range. Test scores were standardized to the controls for age and grouped a priori into composites that reflected performance in six functional domains: executive functions, short-term memory, upper limb motor ability, declarative memory, visuospatial abilities, and gait and balance. Analogous verbal and nonverbal materials and left- and right-hand upper limb motor tasks were used to test whether alcohol-related deficits were greater for left or right hemisphere.Compared with controls, the alcoholics were impaired on executive functions, visuospatial abilities, and gait and balance even after we accounted for group differences in estimated premorbid IQ and education. Within the alcoholic group, the most salient deficits were in gait and balance and visuospatial abilities. No consistent lateralized deficit was observed across the four domains tested. Unlike the cognitive composites, the upper limb motor ability and gait and balance composites both showed increasing vulnerability to age, with an independent contribution to the gait and balance dysfunction from the amount of alcohol consumed over a lifetime.The pattern of functional deficits implicates at least two principal neural systems: the cerebellar-frontal system and the corticocortical system between the prefrontal and parietal cortices. In addition, age and amount of alcohol consumption were better predictors of motor than cognitive impairments.
View details for Web of Science ID 000087216000005
View details for PubMedID 10832902
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fMRI activation patterns of attention and working memory in alcoholics
ELSEVIER SCIENCE INC. 2000: 101S–101S
View details for Web of Science ID 000086515200332
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Sex differences in the corpus callosum of chronically ill schizophrenic patients
ELSEVIER SCIENCE INC. 2000: 39S–39S
View details for Web of Science ID 000086515200127
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Longitudinal changes in cognition, gait, and balance in abstinent and relapsed alcoholic men: Relationships to changes in brain structure
NEUROPSYCHOLOGY
2000; 14 (2): 178-188
Abstract
Chronic alcoholism is associated with cognitive and motor deficits, and there is evidence for reversibility with sobriety. Alcoholic men were examined after 1 month of sobriety and 2 to 12 months later with cognitive and motor tests and magnetic resonance imaging. In this naturalistic study, 20 alcoholic participants had abstained and 22 had resumed drinking at retesting. Abstainers sustained greater improvement than relapsers on tests of delayed recall of drawings, visuospatial function, attention, gait, and balance. Shrinkage in 3rd ventricle volume across all participants significantly correlated with improvement in nonverbal short-term memory. Additional brain structure-function relationships, most involving short-term memory, were observed when analyses were restricted to alcoholic men who had maintained complete abstinence, were light relapsers for at least 3 months, or had consumed no more than 10 drinks prior to follow-up testing. Thus, alcoholic men who maintain abstinence can show substantial functional improvement that is related to improvement in brain structure condition.
View details for DOI 10.1037//0894-4105.14.2.178
View details for Web of Science ID 000087480700002
View details for PubMedID 10791858
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Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease
Annual Meeting of the International-Neuropsychological-Society
AMER PSYCHOLOGICAL ASSOC. 2000: 265–76
Abstract
Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.
View details for DOI 10.1037//0894-4105.14.2.265
View details for Web of Science ID 000087480700010
View details for PubMedID 10791866
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Trait and state aspects of P300 amplitude reduction in schizophrenia: A retrospective longitudinal study
BIOLOGICAL PSYCHIATRY
2000; 47 (5): 434-449
Abstract
The P300 component of the auditory event-related brain potential (ERP) is consistently reduced in schizophrenia. Longitudinal data are examined to determine whether P300 amplitude is a trait marker of schizophrenia or a state marker tracking clinical fluctuations over time.Schizophrenic men (DSM-III-R) (n = 36) received ERP and the Brief Psychiatric Rating Scale (BPRS) assessments on multiple occasions, at varying intervals, under varying medication states. Automatically elicited auditory P3a and effortfully elicited auditory and visual P3b amplitudes were assessed. Brief Psychiatric Rating Scale scores were regressed on P300 amplitude within patients using both multiple regression models and nonparametric analyses of individual patient slopes. Event related brain potentials in patients were compared to ERPs from 34 age-matched control men, and stability of P300 over time was estimated with intraclass correlations.P300 amplitude, regardless of elicitation method or sensory modality, tracked BPRS Total and positive symptom scores over time, decreasing with symptom exacerbations and increasing with improvements. In addition, effortful auditory and visual P3b amplitudes tracked negative symptoms, and automatic auditory P3a tracked depression-anxiety symptoms. When analyses were limited to unmedicated occasions, auditory P3a and P3b persisted in tracking BPRS Total scores, with additional tracking of positive symptoms by P3b and mood symptoms by P3a. Mean auditory and visual P3bs, averaged over all measurement occasions for each individual, were inversely related to mean negative symptoms. Auditory P3a and P3b, but not visual P3b, amplitudes were smaller in patients than control subjects, even when patients were least symptomatic. P300 amplitudes showed high test-retest reliability in control subjects and patients and moderate stability over time in patients.Auditory, and possibly visual, P300 amplitudes track fluctuations in clinical state, but only auditory P300 amplitude is a trait marker of schizophrenia.
View details for Web of Science ID 000085721400008
View details for PubMedID 10704955
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P300 reduction and prolongation with illness duration in schizophrenia
BIOLOGICAL PSYCHIATRY
2000; 47 (5): 413-427
Abstract
The P300 component of the auditory event-related potential (ERP) is both reduced in amplitude and delayed in schizophrenia. P300 is prolonged and, less consistently, reduced with normal aging. Additional latency delays are observed in neurodegenerative disorders. We asked whether P300 is reduced and delayed with longer illness duration in schizophrenia, consistent with a neurodegenerative process.P300 amplitude and latency were recorded to infrequent auditory target stimuli from 35 men with schizophrenia (DSM-III-R) and 26 control men. Effects of current age, age of onset, and duration of illness on P300 were assessed using regression analysis.P300 amplitude showed no age-related decrease in either group; however, among schizophrenic participants, P300 amplitude correlated positively with onset age and negatively with illness duration. P300 latency correlated positively with age in schizophrenic participants and also tended to increase with age in controls. Slopes of the latency-age relationships were significantly greater in schizophrenic participants than in control participants. Latency also correlated positively with illness duration but showed no relationship to onset age.P300 amplitude and latency are reduced and delayed with longer illness duration in schizophrenia, consistent with a progressive pathophysiological process. Reduced P300 amplitude may also be a marker of an early onset variant of schizophrenia.
View details for Web of Science ID 000085721400006
View details for PubMedID 10704953
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alpha 2 macroglobulin and the risk of Alzheimer's disease
NEUROLOGY
2000; 54 (2): 438-442
Abstract
alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56).We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism.We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors.Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.
View details for Web of Science ID 000085043800030
View details for PubMedID 10668709
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Structural brain correlates of verbal and nonverbal fluency measures in Alzheimer's disease
26th Annual Meeting of the International-Neuropsychological-Society
AMER PSYCHOLOGICAL ASSOC. 2000: 29–40
Abstract
This study examined the relationships between regional brain volumes and semantic, phonological, and nonverbal fluency in 32 participants with Alzheimer's disease (AD). Object but not animal semantic fluency correlated with frontal and temporal gray matter volumes. Phonological fluency was not significantly associated with any brain volume examined. Nonverbal fluency was selectively associated with bilateral frontal gray matter volumes. Hippocampal volumes, although markedly reduced in these patients, were not related to any of the fluency measures. Results lend evidence to the importance of the frontal lobes in the directed generation of nonverbal and verbal exemplars by AD patients. Furthermore, both left- and right-hemisphere regions contribute to the generation of verbal and nonverbal exemplars.
View details for Web of Science ID 000085020000003
View details for PubMedID 10674796
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Brain structure in men remains highly heritable in the seventh and eighth decades of life
NEUROBIOLOGY OF AGING
2000; 21 (1): 63-74
Abstract
The midsagittal cross-sectional dimensions of the corpus callosum, the coronal cross-sectional area of the lateral ventricles at the level of the pons, and a three-dimensional estimate of intracranial volume were derived from magnetic resonance brain images obtained from 45 monozygotic and 40 dizygotic male twin pairs aged 68 to 78. Univariate genetic analyses indicated strong genetic influences contributing significantly to the variability of each brain structure. The estimated proportion of genetic variance (i.e. heritability) was 81% for intracranial volume, 79% for the midline cross-sectional area of the corpus callosum, and 79% for lateral ventricle size. There was no evidence that shared environmental influences contributed significantly to twin-pair similarities. We further used bivariate genetic modeling to estimate the genetic and environmental correlation between correlated brain structures. Intracranial volume and corpus callosum area was highly correlated, and this relationship was entirely due to shared genetic effects between these two brain structures. By contrast, the relationship between the height of the corpus callosum and the size of the lateral ventricles was due to both genetic and environmental influences in common. Corresponding genetic and environmental correlations were 0.68 and 0.58, respectively, indicating that more than half of the genetic and environmental influences on these two brain structures were shared. The manner in which the brain responds to the environment with advancing age is highly genetically determined, both for the lateral ventricles, which dilate with aging and disease, and for the corpus callosum, which is deformed in shape by age-related ventricular enlargement, whereas its midline cross-sectional area remains unchanged.
View details for Web of Science ID 000086931500009
View details for PubMedID 10794850
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Cortical gray matter deficit in patients with bipolar disorder
SCHIZOPHRENIA RESEARCH
1999; 40 (3): 219-227
Abstract
cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established.global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence.relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients.this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.
View details for Web of Science ID 000084023000006
View details for PubMedID 10638860
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In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1999; 23 (10): 1629-1636
Abstract
Neuropathological studies use the presence of mammillary body (MB) pathology as a cardinal, diagnostic feature of Wernicke's encephalopathy (WE) in neuropsychiatric diseases, most notably alcoholism. Although Korsakoffs Syndrome (KS), which is marked behaviorally by dense global amnesia, is a typical sequela of WE, it remains controversial whether these two conditions necessarily co-occur and whether MB pathology is therefore a diagnostic requisite for KS.We investigated these issues by examining, in vivo, 24 nonamnesic alcoholics (ALC), 5 amnesic alcoholics (KS), and 51 normal controls with three-dimensional MRI and memory testing. MB volume was determined from successive, 1 mm thick slices.The ALC group had significantly smaller MB volumes bilaterally (mean = 54.5 +/- 22.0 mm3) than controls (mean = 66.3 +/- 17.1 mm3), and the KS group had even smaller MB volumes than the ALC group (mean = 20.7 +/- 14.8 mm3). Only 2 ALC patients met historical clinical criteria for past WE, and their MB volumes were well within range of the remaining 22 ALC patients. Although all five KS patients met historical clinical criteria for WE, three KS did not have accompanying dementia and had the same degree of MB volume loss as the ALC; the remaining two KS had accompanying dementia and MB volumes half the volume of the ALC group and of KS patients without dementia.These findings provide volumetric in vivo evidence that: (1) MB volume deficits do occur in alcoholics without amnesia, although these deficits are not present in ail such alcoholics; (2) greater MB volume deficits are present in alcoholics with clinically detectable amnesia or dementia; (3) MB shrinkage is related to severity of cognitive and memory dysfunction, which suggests a continuum of MB pathology in chronic alcoholism to KS; and (4) the presence of WE in all of the KS patients and in the two ALC patients with the greatest long-term declarative memory deficit supports the possibility of an additional and unique pathology distinguishing nonamnesic and amnesic alcoholism.
View details for Web of Science ID 000083279500011
View details for PubMedID 10549995
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N-acetyl aspartic acid (NAA) and N-acetyl aspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid
NEUROCHEMICAL RESEARCH
1999; 24 (10): 1249-1261
Abstract
N-Acetylaspartic and N-acetylaspartylglutamic acid concentrations in human ventricular, subarachnoid and lumbar cerebrospinal fluid were measured by combined gas chromatography-mass spectrometry using selected ion monitoring with deuterated internal standards. N-Acetylaspartate concentrations were in the range 55, 9, and 1 microM, respectively; N-acetylaspartylglutamate concentrations in the same fluids were in the range 8, 3 and 4 microM, respectively. There did not appear to be any difference in lumbar fluid concentrations of either compound between control subjects, schizophrenic patients, Alzheimer's disease patients and a pooled group of patients with neurological degeneration. Ventricular concentrations of both compounds were greatly increased in deceased patients suggesting that maintenance of their intracellular concentrations is probably energy dependent. The concentrations of these compounds in lumbar cerebrospinal fluid from living, and ventricular cerebrospinal fluid from deceased subjects were weakly correlated with one another. In lumbar fluid neither compound appeared to be correlated with age. Analysis of serially collected lumbar samples from two subjects showed a weak concentration gradient for both compounds. Neither antipsychotic medication nor the acid transport inhibitor probenecid had any effect on lumbar concentrations of either compound. Attempts to use anion exchange high pressure liquid chromatography with UV detection for measurement of the low concentrations of N-acetylaspartate found in cerebrospinal fluid from living subjects were unsuccessful.
View details for Web of Science ID 000082409500007
View details for PubMedID 10492520
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Brain structural and cognitive correlates of clock drawing performance in Alzheimer's disease
26th Annual Meeting of the International-Neuropsychological-Society
CAMBRIDGE UNIV PRESS. 1999: 502–9
Abstract
The Clock Drawing Test (CDT) is widely used in the assessment of dementia and is known to be sensitive to the detection of deficits in neurodegenerative disorders such as Alzheimer's disease (AD). CDT performance is dependent not only on visuospatial and constructional abilities, but also on conceptual and executive functioning; therefore, it is likely to be mediated by multiple brain regions. The purpose of the present study was to identify component cognitive processes and regional cortical volumes that contribute to CDT performance in AD. In 29 patients with probable AD, CDT performance was significantly related to right-, but not left-hemisphere, regional gray matter volume. Specifically, CDT score correlated significantly with the right anterior and posterior superior temporal lobe volumes. CDT scores showed significant relationships with tests of semantic knowledge, executive function, and visuoconstruction, and receptive language. These results suggest that in AD patients, CDT performance is attributable to impairment in multiple cognitive domains but is related specifically to regional volume loss of right temporal cortex.
View details for Web of Science ID 000083339700003
View details for PubMedID 10561930
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Brain gray and white matter transverse relaxation time in schizophrenia
7th International Congress on Schizophrenia Research
ELSEVIER IRELAND LTD. 1999: 93–100
Abstract
Recent in vivo diffusion brain imaging studies of schizophrenic patients have revealed microstructural abnormalities, with low diffusion anisotropy present throughout much of cortical white matter. Brain anisotropy is produced when proton movement reflects physically restricted water movement, for example, by myelin sheaths. Conditions that increase self-diffusion, such as edema, may also alter the longitudinal and transverse relaxation time of protons, and it is possible that such changes could explain the observed anisotropy diminution seen in schizophrenia. To test this possibility, we calculated pixel-by-pixel transverse relaxation time (T2) and proton density (PD) maps for gray matter and white matter across eight 5-mm-thick axial slices of fast spin echo MRI in 10 control men (age 30-57 years) and 10 men with schizophrenia (age 32-64 years). Schizophrenics had significantly longer mean white matter T2 (84.0 vs. 81.9 ms, P<0.03) and gray matter T2 (95.1 vs. 92.2, P = 0.003); their mean white and gray matter PD values were not significantly different from those of controls. Correlations were not significant between anisotropy and T2 in either grey or white matter but were significant between anisotropy and PD in white matter. T2 relaxation times are longer in schizophrenics than in controls in both gray and white matter whereas anisotropy reduction is restricted to white matter. Taken together, these results suggest that the process producing prolonged T2 does not fully account for the abnormally low anisotropy observed selectively in white matter in this group of schizophrenic patients.
View details for Web of Science ID 000082888500003
View details for PubMedID 10515464
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P300 amplitude is related to clinical state in severely and moderately ill patients with schizophrenia
Meeting of the Biological-Psychiatry-Society
ELSEVIER SCIENCE INC. 1999: 94–101
Abstract
Relationships between illness severity and neurobiologic abnormalities in schizophrenia were studied in subpopulations varying in clinical severity.Auditory ERPs were collected from 28 severely ill, chronically hospitalized schizophrenic men from a state hospital; 29 moderately ill inpatient and outpatient schizophrenic men from a veterans hospital; and 30 healthy male subjects from the community as controls. Clinical symptoms were evaluated in patients using the Brief Psychiatric Rating Scale (BPRS).Both schizophrenic patient groups had smaller P300 amplitude than the control subjects. Severely ill patients had smaller P300s than moderately ill patients and scored higher on three BPRS factor scores as well as BPRS Total. Among severely ill patients, P300 amplitude was unrelated to clinical symptoms. Among moderately ill patients, P300 was related to Withdrawal/Retardation, Anxiety/Depression, and BPRS Total. After combining patients, Thinking Disturbance emerged as an additional correlate of P300. Group differences in P300 could not be accounted for by group differences in symptom severity using analysis of covariance.Reduced P300 amplitude marks the diagnosis of schizophrenia, but also reflects individual differences in severity, including positive symptoms. Previous failures to find relationships between positive symptoms and P300 may have been due to a restricted range of clinical severity.
View details for Web of Science ID 000081103400012
View details for PubMedID 10394478
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Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification
SCHIZOPHRENIA RESEARCH
1999; 37 (2): 149-163
Abstract
Noises elicit startle blinks that are inhibited when immediately (approximately 100 ms) preceded by non-startling prepulses, perhaps reflecting automatic sensory gating. Startle blinks are facilitated when preceded by prepulses at longer lead intervals, perhaps reflecting strategic processes. Event-related brain potentials (ERPs) and startle blinks were used to investigate the well-documented prepulse inhibition failure in schizophrenia. Blinks and ERPs were recorded from 15 schizophrenic men and 20 age-matched controls to noises alone and to noises preceded by prepulses at 120 (PP120), 500 (PP500) and 4000 ms (PP4000) lead intervals. Neither blinks nor any of the ERP components elicited by the noise alone differentiated schizophrenics from controls, although responses to noises were modified by prepulses differently in the two groups. With the N1 component of the ERP, patients showed normal inhibition but lacked facilitation, and with P2, patients lacked inhibition, but showed normal facilitation. With reflex blinks and P300, inhibition was seen in both groups, but no facilitation. These results suggest that different neural circuits are involved in blink and cortical reflections of startle modification in schizophrenics and controls, with both automatic and strategic processes being impaired in schizophrenia.
View details for Web of Science ID 000080583700003
View details for PubMedID 10374650
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Temporal and extra-temporal MRI abnormalities in interictal schizophrenia
ELSEVIER SCIENCE INC. 1999: 116S–116S
View details for Web of Science ID 000079911600372
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Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging
ARCHIVES OF GENERAL PSYCHIATRY
1999; 56 (4): 367-374
Abstract
Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo.Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging.Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions.Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.
View details for Web of Science ID 000079504400011
View details for PubMedID 10197834
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Profile of cognitive deficits in schizophrenics comorbid for alcoholism
ELSEVIER SCIENCE BV. 1999: 156–56
View details for Web of Science ID 000079061400443
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In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease
ARCHIVES OF GENERAL PSYCHIATRY
1999; 56 (2): 185-192
Abstract
Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functionally compromised can be estimated in vivo with magnetic resonance spectroscopic imaging.To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation.Fifteen healthy young individuals, 19 healthy elderly individuals, and 16 patients with AD underwent 3-dimensional magnetic resonance spectroscopic imaging and memory and language testing.Gray matter N-acetyl compound concentrations (signal intensity corrected for the amount of brain tissue contributing to the magnetic resonance spectroscopic imaging signal) was significantly reduced only in patients with AD, even though both the AD and elderly control groups had substantial gray matter volume deficits relative to the young control group. Both the healthy elderly and AD groups had abnormally high gray matter creatine plus phosphocreatine concentrations. Gray matter choline concentrations were higher in the elderly than the younger controls, and even higher in the AD group than in the elderly control group. Functional significance of these findings was supported by correlations between poorer performance on recognition memory tests and lower gray matter N-acetyl compounds in elderly controls and higher gray matter creatine plus phosphocreatine and choline concentrations in patients with AD.Cortical gray matter volume deficits in patients with AD are accompanied by disease-related increases in gray matter choline concentrations suggestive of cellular degeneration and reduced N-acetyl compound concentrations, with possible effects on behavioral function.
View details for Web of Science ID 000078553600010
View details for PubMedID 10025444
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In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: Effects of normal aging
MAGNETIC RESONANCE IN MEDICINE
1999; 41 (2): 276-284
Abstract
Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N-acetyl-moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age-related changes in brain MRS metabolites.
View details for Web of Science ID 000078804500010
View details for PubMedID 10080274
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Severity of schizophrenia and magnetic resonance imaging abnormalities: A comparison of state and veterans hospital patients
6th International Congress on Schizophrenia Research
ELSEVIER SCIENCE INC. 1999: 49–61
Abstract
The relationship between illness severity and neuroanatomical abnormalities in schizophrenia remains unclear. The purpose of this study was to test whether the pattern and extent of brain volume abnormalities differed between two patient groups, distinguished by their overall severity and clinical course of schizophrenia.Subjects were 56 severely ill, chronically hospitalized schizophrenic men from Napa State Hospital (SH-SZ), 44 moderately ill, acutely hospitalized schizophrenic men from the Palo Alto Veterans Administration Health Care System (VA-SZ), and 52 healthy male control subjects. Temporolimbic, ventricular, and frontoparietal volumes, quantified from 3-mm coronal spin-echo magnetic resonance images and adjusted for cerebral volume and age, were compared using analysis of variance.Compared to control subjects, both SZ groups had smaller (p < .05) temporal lobe and frontoparietal gray matter volumes and larger ventricles and temporal sulci. Whereas SH-SZ had more pronounced cerebrospinal fluid and frontoparietal abnormalities relative to VA-SZ; VA-SZ had greater temporal lobe gray matter deficits. Neither patients group had hippocampal or cerebral volume deficits relative to control subjects. There were no differences between diagnostic subtypes.The magnitude of volume abnormalities in schizophrenia varies with respect to disease severity and to brain region, but disease severity is not associated with anatomically distinct subgroups.
View details for Web of Science ID 000077967900006
View details for PubMedID 9894575
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Cerebrospinal fluid glutamate inversely correlates with positive symptom severity in unmedicated male schizophrenic/schizoaffective patients
BIOLOGICAL PSYCHIATRY
1999; 45 (1): 68-75
Abstract
Recent hypotheses have suggested that diminished brain glutamate may be of importance in the neurochemical basis of schizophrenia.We assayed cerebrospinal fluid for glutamate and obtained clinical symptom ratings in 19 medication-free (except p.r.n. chloral hydrate) schizophrenic or schizoaffective (typically with significant schizophrenic qualities) male inpatients.Ratings of positive symptoms were significantly inversely correlated (rs = -.457, p < .05, one-tailed test) with glutamate concentrations. Hallucinatory behavior was strongly correlated (rs = -.621, p < .01, one-tailed test) with glutamate. A subset of 11 patients consented to a second lumbar puncture (LP) after treatment with haloperidol (typically 15 or 20 mg/day) for 2-4 weeks. Haloperidol treatment did not alter glutamate concentrations. No correlations were noted between glutamate and symptoms in the medicated subsample. Though approximately half the patients received chloral hydrate during the 72 hours prior to the unmedicated LP, the correlations between positive symptoms and glutamate in the patients who received no chloral hydrate prior to the LP were quite similar to those found in the overall sample.The results provide further support for the potential importance of glutamate in the neurochemical basis of schizophrenia.
View details for Web of Science ID 000077967900008
View details for PubMedID 9894577
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Fluency performance patterns in Alzheimer's disease and Parkinson's disease
CLINICAL NEUROPSYCHOLOGIST
1998; 12 (4): 487-499
View details for Web of Science ID 000080699400005
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A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval
Annual Meeting of the Research-Society-on-Alcoholism
AMER MEDICAL ASSOC. 1998: 905–12
Abstract
We report on structural brain changes during a 5-year period in healthy control and alcoholic men.Alcoholic patients (n = 16), from an initial group of 58 who underwent brain magnetic resonance imaging scanning while in treatment, were rescanned with the same acquisition sequence approximately 5 years later. Control subjects (n = 28) spanning the same age range also were scanned twice at a comparable interval. Changes in brain volume were corrected for error due to differences in head placement between scans and expressed as slopes (cubic centimeters per year), percentage of change over baseline for the control subjects, and standardized change for the alcoholic patients. The alcoholic patients varied considerably in the percentage of time that symptoms of alcohol dependence were present and in the amount of alcohol consumed during follow-up.The cortical gray matter diminished in volume over time in the control subjects, most prominently in the prefrontal cortex, while the lateral and third ventricles enlarged. The alcoholic patients showed similar age-related changes with a greater rate of gray matter volume loss than the control subjects in the anterior superior temporal lobe. The amount of alcohol consumed during follow-up predicted the rate of cortical gray matter volume loss, as well as sulcal expansion. The rate of ventricular enlargement in alcoholic patients who maintained virtual sobriety was comparable to that in the control subjects.During a 5-year period, brain volume shrinkage is exaggerated in the prefrontal cortex in normal aging with additional loss in the anterior superior temporal cortex in alcoholism. The association of cortical gray matter volume reduction with alcohol consumption over time suggests that continued alcohol abuse results in progressive brain tissue volume shrinkage.
View details for Web of Science ID 000076415500008
View details for PubMedID 9783561
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Differential contributions of cognitive and motor component processes to physical and instrumental activities of daily living in Parkinson's disease
ARCHIVES OF CLINICAL NEUROPSYCHOLOGY
1998; 13 (7): 575-583
Abstract
Patients with Parkinson's disease (PD) become dependent upon caregivers because motor and cognitive disabilities interfere with their ability to carry out activities of daily living (ADLs). However, PD patients display diverse motor and cognitive symptoms, and it is not yet known which are most responsible for ADL dysfunction. The purpose of this study was to identify the contributions that specific cognitive and motor functions make to ADLs. Executive functioning, in particular sequencing, was a significant independent predictor of instrumental ADLs whereas simple motor functioning was not. By contrast, simple motor functioning, but not executive functioning, was a significant independent predictor of physical ADLs. Dementia severity, as measured by the Dementia Rating Scale, was significantly correlated with instrumental but not physical ADLs. The identification of selective relationships between motor and cognitive functioning and ADLs may ultimately provide a model for evaluating the benefits and limitations of different treatments for PD.
View details for Web of Science ID 000075851200001
View details for PubMedID 14590618
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Association between regional brain volumes and clozapine response in schizophrenia
BIOLOGICAL PSYCHIATRY
1998; 43 (12): 879-886
Abstract
Clozapine has shown considerable therapeutic promise in the treatment of schizophrenia; however, the clinical risks and initial high treatment costs associated with its administration motivate the search to identify patients who will best respond. Neuroimaging studies have suggested that prefrontal sulcal prominence may be a predictor of nonresponsiveness.We used magnetic resonance imaging (MRI) to test whether volumes in any cortical regions of the brain were associated with symptom improvement with clozapine treatment. The 21 schizophrenic men studied were clinically evaluated during treatment with typical neuroleptics (baseline) and after a mean of 6.2 months treatment with clozapine (final dose 300-900, median = 562 mg/day). At least a 20% improvement on total Brief Psychiatric Rating Scale (BPRS) was seen in 47.6% of the schizophrenics. Clinical improvement was regressed on baseline differences in clinical severity, and the residual scores were related to MRI values.Patients with larger anterior superior temporal lobe cerebrospinal fluid volumes (primarily sylvian fissure) showed greater improvement on total BPRS and withdrawal/retardation symptoms.Even schizophrenics with significant brain dysmorphology can have a positive clinical response to clozapine.
View details for Web of Science ID 000074039800005
View details for PubMedID 9627742
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Differential activation of dorsal basal ganglia during externally and self paced sequences of arm movements
NEUROREPORT
1998; 9 (7): 1567-1573
Abstract
The basal ganglia are thought to be critically involved in motor control. However, the relative contributions of the various sub-components are not known. Although, in principle, functional magnetic resonance imaging (fMRI) provides adequate resolution to image the basal ganglia at the spatial scale of the individual nuclei, activating these nuclei with fMRI has proven to be difficult. Here we report two tasks, involving externally and self paced sequences of arm movements, which resulted in significant activation of contralateral posterior (post-commissural) putamen and globus pallidus. This activation did not significantly differ between the tasks. In contrast, significant activation of the contralateral and ipsilateral anterior caudate and anterior putamen was observed only during externally paced arm movements. These results suggest a dissociation in the roles of the anterior and posterior dorsal basal ganglia: the anterior caudate and putamen may be involved in sensory to motor mapping and the posterior putamen and globus pallidus may be involved in the motor response itself. The findings support the hypothesis that the basal ganglia may be involved in gating sensory influences onto motor areas.
View details for Web of Science ID 000074000000061
View details for PubMedID 9631468
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Cerebellar signs in schizophrenia and alcoholism
ELSEVIER SCIENCE INC. 1998: 119S–119S
View details for Web of Science ID 000073240700400
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Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia
6th International Congress on Schizophrenia Research
AMER MEDICAL ASSOC. 1998: 346–52
Abstract
To apply in vivo proton magnetic resonance spectroscopy imaging estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative contribution of neuronal and glial changes to the widespread volume deficit of cortical gray matter seen in patients with schizophrenia with magnetic resonance images.Ten male veterans meeting criteria of the DSM-IV, for schizophrenia and 9 healthy age-matched men for comparison were scanned using spectroscopic, anatomical, and field-map sequences. Instrument and collection variables were standardized to allow an estimation of comparable values for NAA, choline, and creatine for all subjects. Metabolite values from each voxel on 3 upper cortical slices were regressed against the gray tissue proportion of that voxel to derive estimates of gray and white matter NAA, creatine, and choline concentrations.The volume of cortical gray matter was reduced in patients with schizophrenia, but NAA signal intensity from a comparable region was normal. In contrast, the volume of cortical white matter was normal in patients with schizophrenia, but NAA signal intensity from a comparable region was reduced.The lack of reduction in gray matter NAA signal intensity suggests that the cortical gray matter deficit in these patients involved both neuronal and glial compartments rather than a neurodegenerative process in which there is a decrease in the neuronal relative to the glial compartment. Reduced white matter NAA signal intensity without a white matter volume deficit may reflect abnormal axonal connections.
View details for Web of Science ID 000072993300009
View details for PubMedID 9554430
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Profile of cortical gray matter volume deficits characteristic of schizophrenia
51st Annual Meeting of the Society-of-Biological-Psychiatry
OXFORD UNIV PRESS INC. 1998: 117–24
Abstract
Quantitative magnetic resonance imaging (MRI) studies from our laboratory have reported that patients with schizophrenia show a widespread cortical gray matter volume deficit, which is especially pronounced in the prefrontal and anterior superior temporal cortices. The present study compared two separate samples of schizophrenic patients -- 71 men from a Veterans Administration (VA) hospital and a sample of 57 severely ill men from a state hospital (SH) -- in an effort to test whether the pattern of brain volume abnormalities previously observed in VA schizophrenic patients can be generalized to other groups of schizophrenic patients. MRI-derived brain volumes of gray matter, white matter and sulcal cerebrospinal fluid (CSF) in six cortical regions, and CSF in the lateral and third ventricles were computed. All MRI volumes were adjusted for normal variation in head size and age and were expressed as standardized Z-scores, which also permitted structures of different sizes to be compared directly. The two schizophrenic groups displayed similar patterns of volume abnormalities: cortical gray matter but not white matter volume deficits that were widespread but especially notable in the prefrontal and temporal regions. The regional gray matter deficits in the SH group were generally greater than those in the VA group, particularly in the prefrontal and posterior superior temporal regions. Both schizophrenic groups had abnormally large volumes of the cortical sulci and lateral and third ventricles; however, the SH group showed greater enlargements, the most prominent occurring in the ventricles and temporal sulci. The overlapping patterns of cortical gray matter deficits in the two groups provide evidence for generality of this pattern of regional brain volume abnormalities in schizophrenia.
View details for Web of Science ID 000072118300003
View details for PubMedID 9542891
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Structural MRI correlates of recognition memory in Alzheimer's disease
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
1998; 4 (2): 106-114
Abstract
Neuroimaging and lesion studies have demonstrated that hippocampal volume correlates with memory performance, but material-specific lateralization of this structure-function relationship has been inconsistent. This MRI study examined the relative contributions of left and right temporal lobe volumes to verbal and nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients. There was a significant relationship between extent of right hippocampal and right temporal gray matter tissue volume deficit and performance on the face recognition subtest of the Warrington Recognition Memory Test. The face recognition test correlated with right hemisphere volume but not to left, indicating a material-specific relationship between brain structure and function in this patient group. Right temporal horn volume did not account for a significant proportion of variance in face recognition memory. Although word recognition was not significantly correlated with either left or right hippocampal volume in the total group, there was a strong correlation between left hippocampal volume and word recognition memory in the female AD patients. Thus, face recognition shows a material specific relationship with select lateralized hippocampal and temporal cortical volumes in AD patients, regardless of gender, whereas the verbal recognition-left-hippocampal volume relationship may be mediated by gender.
View details for Web of Science ID 000075146200002
View details for PubMedID 9529820
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Patterns of regional cortical dysmorphology distinguishing schizophrenia and chronic alcoholism
5th International Congress on Schizophrenia Research
ELSEVIER SCIENCE INC. 1998: 118–31
Abstract
This study used magnetic resonance imaging (MRI) to compare the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in chronic alcoholics and schizophrenics.The subjects included 62 detoxified chronic alcoholics (26-63 years), 71 schizophrenics (23-63 years), and 73 controls spanning the adult age range (21-70 years). MRI volumes were adjusted for normal variation in head size and age established from the control group.Both patient groups showed widespread cortical gray matter volume deficits compared with controls, but only the alcoholics had white matter volume deficits. The schizophrenics had significantly greater volume deficits in the prefrontal and anterior superior temporal gray matter than in the more posterior cortical regions. By contrast, the deficits in the alcoholics were relatively homogeneous across the cortex. For white matter, the deficits in the alcoholics were greatest in the prefrontal and temporal-parietal regions. Although both patient groups had abnormally larger cortical sulci and lateral and third ventricles than the controls, the alcoholics had significantly larger sulcal volumes in the frontal, anterior, and posterior parietal-occipital regions than the schizophrenics.This quantitative MRI study revealed different patterns of regional cortical volume abnormalities in schizophrenics and alcoholics. The schizophrenic group exhibited cortical gray matter volume deficits of modestly greater magnitude than that observed in the alcoholic group, and the alcoholics but not the schizophrenics exhibited cortical white matter volume deficits.
View details for Web of Science ID 000072093000005
View details for PubMedID 9474444
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Structural magnetic resonance imaging abnormalities in men with severe chronic schizophrenia and an early age at clinical onset
ARCHIVES OF GENERAL PSYCHIATRY
1997; 54 (12): 1104-1112
Abstract
Early age at onset of schizophrenia often signifies a more severe form of the illness. However, the relationship between age at onset and brain abnormalities has not been established. We assessed temporal-limbic morphometry in severely ill men with chronic schizophrenia who had a relatively early onset of illness and examined the relationships among regional brain volumes, clinical symptoms, and age at illness onset.Temporal lobe, superior temporal gyrus, hippocampus, temporal horn, lateral ventricles, third ventricle, and frontoparietal volumes were measured on magnetic resonance imaging data from 56 schizophrenic men (mean [SD] age at illness onset, 16.6 [4.2] years) recruited from a state hospital and 52 age- and range-matched healthy control men.Patients had significantly smaller gray matter volumes in the temporal lobe, superior temporal gyrus, and frontoparietal regions; smaller temporal lobe white matter volumes; and larger cerebrospinal fluid volumes for temporal lobe sulci and the 3 ventricular measures. There were no group differences in hippocampal volumes. Psychotic symptom subscores from the Brief Psychiatric Rating Scale were selectively correlated with smaller left posterior superior temporal gyrus gray matter volumes. None of the brain measurements were significantly correlated with age at illness onset.Data from this unique sample of severely ill schizophrenic men emphasize a pattern of structural abnormalities involving the cortex, but not the hippocampus, in schizophrenia. Furthermore, these data support theories suggesting that superior temporal gyrus abnormalities contribute selectively to psychotic symptoms and that the extent of structural abnormalities is unrelated to age of clinical symptom onset.
View details for Web of Science ID A1997YJ96900006
View details for PubMedID 9400346
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Design and efficacy of a head-coil bite bar for reducing movement-related artifacts during functional MRI scanning
BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS
1997; 29 (4): 589-594
View details for Web of Science ID 000071076900015
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Quantification of cerebellar structures with MRI
PSYCHIATRY RESEARCH-NEUROIMAGING
1997; 75 (3): 159-171
Abstract
Methodological issues have limited neuroimaging studies of cerebellar structures. In this article we describe a method that addresses some of these limitations and phantom studies that examine the validity of the image manipulations. We compared volumes derived from 3D Spoiled Gradient Recalled Acquisition MR images sliced with respect to three different alignment methods: one based on cerebellar landmarks, another on cerebral landmarks and a third on the plane of acquisition. Examination of coefficients of variation, coefficients of error and convergent validity suggests that although regional cerebellar volumes based on cerebellar landmarks provide the best estimates of the true volumes, observed differences between volume measurements from alignments based on cerebellar or cerebral landmarks were generally not significant and were inconsequential. In this case, the measure was improved with alignment along local, relevant cerebellar landmarks. A set of phantom experiments showed that realignment, reslicing and interpolation in 3-dimensional image processing exerted, at most, trivial distortion on the estimates of actual object volumes.
View details for Web of Science ID 000071115400003
View details for PubMedID 9437773
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Deficits in multiple systems of working memory in schizophrenia
SCHIZOPHRENIA RESEARCH
1997; 27 (1): 1-10
Abstract
Working memory, the ability to hold and manipulate information 'on-line' in a temporary memory store, is impaired in schizophrenia. This impairment may be characterized within the framework of two opposing theoretical models: (1) central executive as coordinator of component processes of working memory or (2) multiple independent systems of spatial and object memory. In order to test which of these models better explains the working memory deficit of schizophrenia, 14 schizophrenic patients and 12 age- and gender-matched control subjects performed tests of spatial memory (dot location), object memory (shapes, color dots) and a dual paradigm (dot location + shapes). If schizophrenia impairs the central executive, a group-by-task interaction would demonstrate excessively worse performance on the dual than single tasks in schizophrenics relative to controls; however, the absence of an interaction would be consistent with deficits in the multiple working memory systems. The schizophrenic group was significantly impaired on all measures, and both the schizophrenic and control performance was worse on the dual than the single tasks. Despite the schizophrenic group performance deficits on the single tasks, the extent of such deficit did not appear additive and contributive to the dual tasks. The lack of a group-by-task interaction provided no support for the central executive model of dysfunction. Rather, the results uphold the model of working memory deficits arising from compromise of multiple (here spatial and object), relatively independent systems, both of which are affected in schizophrenia.
View details for Web of Science ID A1997YD36900001
View details for PubMedID 9373889
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Combined event-related fMRI and EEG evidence for temporal-parietal cortex activation during target detection
NEUROREPORT
1997; 8 (14): 3029-3037
Abstract
Target detection is the process of bringing a salient stimulus into conscious awareness. Target detection evokes a prominent event-related potential (ERP) component (P3) in the electroencephalogram (EEG). We combined the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of EEG to investigate the neural generators of the P3. Event-related brain activation (ERBA) and ERPs were computed by time-locked averaging of fMRI and EEG, respectively, recorded using the same paradigm in the same subjects. Target detection elicited significantly greater ERBAs bilaterally in the temporal-parietal cortex, thalamus and anterior cingulate. Spatio-temporal modelling of ERPs based on dipole locations derived from the ERBAs indicated that bilateral sources in the temporal-parietal cortex are the main generators of the P3. The findings provide convergent fMRI and EEG evidence for significant activation of the temporal-parietal cortex 285-610 ms after stimulus onset during target detection. The methods developed here provide a novel multimodal neuroimaging technique to investigate the spatio-temporal aspects of processes underlying brain function.
View details for Web of Science ID A1997XX91000009
View details for PubMedID 9331910
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Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease
Annual Meeting of the International-Neuropsychological-Society
AMER MEDICAL ASSOC. 1997: 719–28
Abstract
To examine whether each of the 5 Mattis Dementia Rating Scale (DRS) scores related to magnetic resonance imaging-derived volumes of specific cortical or limbic brain regions in patients with Alzheimer disease (AD).Relations between DRS measures and regional brain volume measures were tested with bivariate and multivariate regression analyses.The Aging Clinical Research Center of the Stanford (Calif) University Department of Psychiatry and Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif.Fifty patients with possible or probable AD. Magnetic resonance imaging data from 136 healthy control participants, age 20 to 84 years, were used to correct brain volumes for normal variation arising from intracranial volume and age.The DRS scores and volumes of regional cortical gray matter and of the hippocampus.Memory scores of the patients with AD were selectively related to hippocampal volumes. Attention and construction scores were related to several anterior brain volume measures, with attention showing a significantly greater association to right than left hemisphere measures. Initiation/perseveration scores were not significantly correlated with any measure of regional gray matter volume, but performance was related to prefrontal sulcal widening, with a greater association with the left than right sulcal volume.Certain DRS subtests are predictably correlated with selective regional brain volumes in AD. The specific relation between memory and hippocampal volumes and the nonsignificant relations between memory and regional cortical volumes suggest a dissociation between cortical and hippocampal contributions to explicit memory performance.
View details for Web of Science ID A1997XE00100008
View details for PubMedID 9193207
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Quetiapine in patients with schizophrenia - A high- and low-dose double-blind comparison with placebo
ARCHIVES OF GENERAL PSYCHIATRY
1997; 54 (6): 549-557
Abstract
Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d).In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests.Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters.Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.
View details for Web of Science ID A1997XE94500007
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Similar extent of brain dysmorphology in severely ill women and men with schizophrenia
5th International Congress of Schizophrenia Research
AMER PSYCHIATRIC PUBLISHING, INC. 1997: 819–25
Abstract
The purpose of this study was to determine whether women with chronic, severe schizophrenia manifest a widespread deficit in cortical gray matter and ventricular enlargement similar to that seen in men with schizophrenia and whether this deficit is related to age at onset of illness, length of illness, or current illness severity.Volumetric measures of head size, cortical gray matter, white matter and sulci, and lateral and third ventricles were obtained from magnetic resonance images of chronic inpatient schizophrenic women (N = 19) and men (N = 18) and healthy comparison women (N = 19) and men (N = 18). Sex and group differences were assessed by using a two-factor analysis of variance of brain measures. Age was entered as a covariate in assessments of associations between brain measures and age at onset and length of illness.The schizophrenic patients as a group had less cortical gray matter but comparable white matter and significantly more lateral and third ventricular CSF than the comparison group. Compared to the combined groups of men, women, regardless of diagnosis, had smaller heads, less cortical gray and white matter, and less sulcal, lateral, and third ventricular CSF. There were no group-by-sex interactions, suggesting that in schizophrenia these aspects of gross volumetric morphology in male and female brains are affected equally. There was no relationship between cortical gray matter deficit or ventricular enlargements and age at symptom onset or length of illness in either men or women with schizophrenia, when variance due to age was accounted for statistically.The process that contributes to cortical gray matter deficit in schizophrenia appears to affect men and women to a similar extent.
View details for Web of Science ID A1997XA58700015
View details for PubMedID 9167510
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Cortical and hippocampal volume deficits in temporal lobe epilepsy
EPILEPSIA
1997; 38 (5): 576-587
Abstract
To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE).Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA).As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.
View details for Web of Science ID A1997WX71900011
View details for PubMedID 9184604
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Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics
Annual Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 1997: 521–29
Abstract
This study used magnetic resonance imaging to quantify the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in younger versus older chronic alcoholics relative to normal controls. In the present analysis, we divided our previously reported group of 62 alcoholic men into a younger group (n = 33, age mean = 37.5 +/- 4.5, and range = 26 to 44 years) and an older group (n = 29, age mean = 52.7 +/- 6.0, and range = 45 to 63 years) to examine whether, in addition to extent, the two age groups differed in pattern of tissue type and regional brain volume abnormalities quantified with magnetic resonance imaging. Brain volumes were adjusted for normal variation in head size and age established from a group of healthy controls and were expressed as Z-scores. The younger group had significant cortical gray, but not white, matter volume deficits and sulcal and ventricular enlargement relative to age-matched controls. The older group had volume deficits in both cortical gray and white matter and sulcal and ventricular enlargement that significantly exceeded the younger alcoholic group. An analysis of six cortical regions revealed that, although both age groups had gray matter volume deficits throughout the cortex, the older alcoholic group had a selectively more severe deficit in prefrontal gray matter relative to the younger alcoholic group. Similarly, the cortical white matter volume deficit in the older alcoholics was especially severe in the prefrontal and frontal regions. The differences in brain dysmorphology between the two alcoholic groups cannot easily be attributed to potential alcohol history differences typically related to age because the two groups had similar disease durations and amounts of lifetime alcohol consumption. These results provide in vivo evidence that the frontal lobes are especially vulnerable to chronic alcoholism in older men.
View details for Web of Science ID A1997WZ64500020
View details for PubMedID 9161613
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Patterns of content, contextual, and working memory impairments in schizophrenia and nonamnesic alcoholism
NEUROPSYCHOLOGY
1997; 11 (2): 195-206
Abstract
This study used tests of content memory (item recognition of words and abstract designs), context memory (order recognition of verbal and nonverbal items), and working memory (recognition at a short retention interval) to examine patterns of performance in 27 schizophrenic patients, 52 chronic alcoholic patients, and 66 healthy control participants. When performance was age- and IQ-adjusted the schizophrenia group was significantly impaired in item and order recognition of verbal and nonverbal material; the alcoholic group was impaired only in order recognition for both material types. Item- and order-recognition deficits in the schizophrenia group were greatest at the shortest retention intervals, a pattern previously observed in patients with Parkinson's disease, suggesting a prominence of a working memory deficit in schizophrenia.
View details for Web of Science ID A1997WT56900004
View details for PubMedID 9110327
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Deficits in procedural learning rate in schizophrenia but not alcoholism
ELSEVIER SCIENCE INC. 1997: 306–306
View details for Web of Science ID A1997WQ70900307
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Automatic and effortful processing in aging and dementia: Event-related brain potentials
NEUROBIOLOGY OF AGING
1997; 18 (2): 169-180
Abstract
Automatic and effortful processes were investigated using event-related brain potentials (ERPs) recorded from moderately impaired subjects with probable Alzheimer's Disease (AD), normal elderly, and normal young controls. The effects of effortful attention on ERPs to loud noises and the effects of stimulus intrusiveness on effortfully elicited ERPs were studied. First, ERPs to task relevant and irrelevant startling noises were compared. Second, ERPs to startling noises and moderate tones were compared when both were targets. The effects of age (young vs. elderly controls) and effects of dementing disease (AD subjects vs. elderly controls) were also assessed. Effortful attention augmented noise-elicited P300 amplitude in elderly subjects, but not in young. Intrusiveness augmented task-relevant P300 amplitude in young subjects, but not in elderly. Neither variable affected P300 amplitude in AD subjects. Thus, effects of age and disease depended on how P300 was elicited: when effortfully elicited, P300 amplitude was affected by disease but not age; when automatically elicited, P300 amplitude was affected by age but not disease. N1 effects differed from P300 effects.
View details for Web of Science ID A1997XP01300006
View details for PubMedID 9258894
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Automatic but not strategic processing is abnormal in schizophrenics
ELSEVIER SCIENCE BV. 1997: 233–33
View details for Web of Science ID A1997WP19600663
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Clinical symptoms and mri abnormalities in schizophrenia and in epilepsy
ELSEVIER SCIENCE BV. 1997: 151–52
View details for Web of Science ID A1997WP19600426
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Working memory deficits in schizophrenia: Dysfunction in multiple systems, not in the central executive
ELSEVIER SCIENCE BV. 1997: 137–37
View details for Web of Science ID A1997WP19600384
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Regional cerebellar volume deficits in schizophrenia, alcoholism and schizophrenia with alcohol comorbidity
ELSEVIER SCIENCE BV. 1997: 142–43
View details for Web of Science ID A1997WP19600399
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Proton spectroscopy reveals normal NAA concentration in cortical gray matter in schizophrenic patients
ELSEVIER SCIENCE BV. 1997: 179–80
View details for Web of Science ID A1997WP19600509
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Effects of 'seroquel' (quetiapine) on platelet serotonin-2 binding in schizophrenia
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
1996; 16 (6): 464-466
View details for Web of Science ID A1996VW91400015
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Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1996; 20 (8): 1489-1495
Abstract
Mammillary body and cerebellar atrophy have been described as postmorten neuropathologic markers of Korsakoff's syndrome. This study examined whether shrinkage in the mammillary bodies and cerebellum is present consistently in amnesic chronic alcoholics during life and whether the degree of abnormality in these patients differs from that in nonamnesic alcoholic and healthy controls. The severity of shrinkage in the mammillary bodies, cerebellar hemispheres, and cerebellar vermis visualizable on MRI scans was rated on a three-point scale in 33 chronic nonamnesic alcoholics, 9 amnesic alcoholics, and 20 healthy controls. Although both alcoholic groups showed significant mammillary body and cerebellar shrinkage relative to controls, the two patient groups did not differ from each other. Furthermore, four of eight amnesic patients in our sample did not demonstrate clinically significant mammillary body atrophy. These results suggest that alcoholism is associated with mammillary body and cerebellar tissue volume loss but do not provide evidence that these markers distinguish accurately between amnesic and nonamnesic patients. In addition, they suggest that visualizable mammillary body atrophy is not necessary for the development of amnesia in alcoholic patients.
View details for Web of Science ID A1996VU64400025
View details for PubMedID 8947329
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The effect of stimulus-response incompatibility on P3 latency depends on the task but not on age
BIOLOGICAL PSYCHOLOGY
1996; 44 (2): 121-141
Abstract
To help identify the loci of age-related slowing of cognitive processing, the effects of stimulus-response (S-R) incompatibility and stimulus degradation on P3 latency and reaction time (RT) were assessed in ten young and ten elderly women. Subjects saw the words right, left, RIGHT, or LEFT in tasks which required responses to (1) the meaning of the word (WORD) (2) its case (CASE) and (3) both (CASE/WORD). Each task was tested with regular and degraded stimuli. On half the trials, the stimulus and response were incompatible. Although RTs and P3s of elderly subjects were slower, especially RTs in CASE/WORD, stimulus degradation and S-R incompatibility did not differentially affect the two groups, suggesting that cognitive processing of older subjects is not especially prolonged in perceptual and response-related stages. For both groups RTs and P3s were task dependent and were prolonged by degradation and S-R incompatibility. Incompatibility delayed RTs in WORD and CASE/WORD but P3s in WORD only. Thus, young and elderly subjects show qualitatively similar psychophysiological and behavioral indicators of processing speed.
View details for Web of Science ID A1996VP86400004
View details for PubMedID 8913525
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Increased fMRI activation of anterior cingulate to infrequent versus frequent stimuli an auditory oddball task
WILEY-BLACKWELL PUBLISHING, INC. 1996: S62–S62
View details for Web of Science ID A1996VF57700244
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Gray matter deficits in young onset schizophrenia are independent of age of onset
BIOLOGICAL PSYCHIATRY
1996; 40 (1): 4-13
Abstract
This study examined whether the degree of brain dysmorphology observable in adulthood was related to onset age of schizophrenic symptoms. Brain magnetic resonance imaging (MRI) scans were acquired in 57 men with schizophrenia, whose age at MRI was 19-53 years, and whose symptom onset ranged from age 7 to 29 years; all were inpatients in a state hospital. Volumes of intracranial space, cortical gray matter (GM) and white matter (WM), and cerebrospinal fluid (CSF) in lateral and third ventricles and cortical sulci were derived from MRI scans and corrected by regression analysis for variations attributable to age and head size, quantified in a control sample of healthy community volunteers. The schizophrenic patients had larger volumes of cortical and ventricular CSF and smaller volumes of cortical GM but not WM than age-matched controls, whether or not volumes were adjusted for head size and age norms. Age of onset did not correlate with any of the five age-adjusted brain measures. Neither current age, length of illness, nor symptom severity correlated with age-normalized volumes of cortical GM, sulcal CSF, or ventricular CSF. These observations are consistent with the theory that brain structure deficits 1) first develop prior to symptom onset (perhaps during the prenatal and/or early childhood process of GM development); 2) probably establish a vulnerability to subsequent dysfunctionality; but 3) are nonprogressive.
View details for Web of Science ID A1996UQ17800002
View details for PubMedID 8780849
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Thinning of the corpus callosum in older alcoholic men: A magnetic resonance imaging study
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1996; 20 (4): 752-757
Abstract
A brain image averaging technique was applied to three-dimensional magnetic resonance images to identify visually detectable brain volume abnormalities in chronically alcoholic men, compared with healthy control men. This technique, which was based on pixel-by-pixel statistical probability mapping, revealed a dramatic reduction in the area of the corpus callosum in older alcoholics (age 45 years or older), relative to age-matched controls. Subsequent analysis used anatomical landmarks to outline the borders of midsagittal sections of the corpus callosum in a larger group of alcoholics and controls, who spanned the adult age range from 23 to 71 years. This analysis revealed significant reduction, most prominent in the genu and body, of total callosal area in the alcoholic group relative to the control group; the results were the same whether raw area measures or head size plus age adjusted measure were analyzed. Significant thinning of the callosal body in alcoholics is usually attributed to the relatively rare, nutritional-deficient condition, Marchiafava-Bignami disease. However, callosal thinning was present in vivo in chronic alcoholics without clinical symptoms of severe liver disease, amnesia, or alcoholic dementia. These data suggest that chronic alcoholism can be characterized by a continuum of graded brain dysmorphology, rather than classical alcoholic-related subsyndromes, such as Marchiafava-Bignami disease.
View details for Web of Science ID A1996UT99900021
View details for PubMedID 8800395
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Cortical gray matter volume deficits in schizophrenia: A replication
SCHIZOPHRENIA RESEARCH
1996; 20 (1-2): 157-164
Abstract
We sought to replicate an earlier finding of widespread deficit in cortical gray matter in schizophrenia by testing new samples of 22 schizophrenic patients and 27 controls between the ages of 21-46 years. Brain values for both patients and controls were standardized against age and head size norms derived from a larger control group (n = 73) spanning a wider age range (21-70). Compared to the new age-matched controls, the new schizophrenic sample showed a deficit in gray matter volume affecting the cortex as a whole and enlargement of the lateral and third ventricles. Thus, widespread cortical gray matter deficit is a replicable feature of the brain dysmorphology of schizophrenia in young to middle-aged men.
View details for Web of Science ID A1996UR72100017
View details for PubMedID 8794504
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Relationship between alcohol withdrawal seizures and temporal lobe white matter volume deficits
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1996; 20 (2): 348-354
Abstract
A previous magnetic resonance imaging study from our laboratory reported significant temporal lobe volume deficits in cortical gray matter, white matter, and anterior hippocampus in chronic alcoholic men relative to controls. In the present study, we reexamined these data and asked whether withdrawal seizure history was predictive of either the hippocampal or the extrahippocampal volume deficits. A review of the medical charts indicated that 11 alcoholics had experienced one or more alcohol-related seizures and 35 were seizure-free; no patient had a seizure disorder unrelated to alcohol. The two alcoholic groups did not differ significantly in age, education, alcohol consumption variables, premorbid intelligence, Memory Quotient, Trail Making, or detection of hidden figures. Although each alcoholic group showed significant bilateral volume deficits of the anterior hippocampus and frontal-parietal and temporal gray matter, relative to controls, the seizure group had significantly smaller temporal lobe white matter volumes than either the control or the seizure-free groups; the latter two groups did not differ from each other. Both alcoholic groups, however, had white matter volume deficits in the frontal-parietal region. Thus, the seizure group accounted for the white matter volume deficits in the temporal lobe previously reported in the full sample of alcoholics. It seems, then, that reduced white matter volume in the temporal lobes may be either a risk factor for or sequela of alcohol withdrawal seizures.
View details for Web of Science ID A1996UE73700023
View details for PubMedID 8730229
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Cluster analysis of MRI regional brain volumes in schizophrenia
ELSEVIER SCIENCE INC. 1996: 478–78
View details for Web of Science ID A1996UE89300463
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A schizophrenia profile of regional cortical gray matter deficits
ELSEVIER SCIENCE INC. 1996: 340–40
View details for Web of Science ID A1996UE89300332
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Cerebellar volume deficits ln schizophrenia
ELSEVIER SCIENCE INC. 1996: 339–39
View details for Web of Science ID A1996UE89300331
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Slow wave sleep and computed tomographic measures of brain morphology in schizophrenia
PSYCHIATRY RESEARCH
1996; 60 (2-3): 125-134
Abstract
To test the hypothesis that slow wave sleep in schizophrenia is inversely correlated with ventricular system volume, polysomnography and computed tomographic (CT) brain imaging were carried out in 14 psychiatric patients who met Research Diagnostic Criteria for schizophrenia (h = 11) or schizoaffective disorder (n = 3). Three measures of ventricular system volume were analyzed: (1) raw ventricular volume expressed in cm3; (2) ventricle-to-brain ratio; and (3) ventricular volume corrected for normal variation in age and head size expressed as a standardized (z) score. All three quantifications of ventricular volume were significantly and inversely correlated with visually scored measures of stage 3 and stage 4 sleep. This finding suggests that the etiology of slow wave sleep deficits in schizophrenia is related either directly or indirectly to underlying brain dysmorphology.
View details for Web of Science ID A1996UH31100005
View details for PubMedID 8723303
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Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia
BIOLOGICAL PSYCHIATRY
1996; 39 (4): 234-240
Abstract
This study examined whether the neuropsychological deficits observed in patients with schizophrenia were related to cortical gray matter volume deficits in these patients. All subjects were men and included 34 patients with DSM-III-R Schizophrenia and 47 age-matched healthy controls. Subjects received a battery of 21 tests, assessing four different functional domains: executive functions, short-term memory and production, declarative memory, and motor ability. MRI volumes were corrected for normal variation in head size and age, and neuropsychological test scores were corrected for normal variation in age. The schizophrenic group had significantly smaller cortical gray matter volumes (p < .05) and lower test scores in all functional domain than the control group (p = .0001). Within the schizophrenic group, lower scores in each domain were significantly correlated with smaller total cortical gray matter volumes; however, no predictable relationships were observed between neuropsychological test performance and the volumes of specific cortical regions.
View details for Web of Science ID A1996TW73000002
View details for PubMedID 8645769
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White matter MR hyperintensities in adult patients with congenital rubella
AMERICAN JOURNAL OF NEURORADIOLOGY
1996; 17 (1): 99-103
Abstract
To observe and quantify white matter hyperintensities on MR images in adults with schizophrenialike symptoms who had had congenital rubella, in order to elucidate the neuropathologic sequelae of this perinatal viral infection and to explore the potential relationship of these lesions to schizophrenia.Eleven deaf adult patients with documented prenatal rubella virus infection and schizophrenialike symptoms were compared with 19 age-matched patients with early-onset schizophrenia who did not have congenital rubella and with 18 age-matched control subjects. All MR images (obtained at 1.5 T) were evaluated by a neuroradiologist who was blinded to diagnosis and were rated for white matter lesions on a five-point scale: 0 = no lesions; 1 = 1 lesion less than 1 mm in diameter; 2 = 1 to 4 lesions 1 mm or greater; 3 = 5 to 10 lesions; 4 = more than 10 lesions or a single lesion more than 1 cm in diameter. In addition, the white matter hyperintensities were volumed objectively with a manual threshold technique.Ratings of white matter lesions were significantly higher in the rubella patients than in the control subjects: 6 of the 11 patients had ratings greater than 1 compared with 1 of the 18 control subjects and none of the 19 schizophrenic patients. Also, MR images in five rubella patients received ratings at the highest end of the scale of abnormality (3 or 4). The white matter hyperintensities were characterized as bilateral T2 signal hyperintensities in periventricular and subcortical regions, punctate or linear in shape; they were observed predominantly in parietal lobes.This quantitative MR study of adult rubella patients disclosed abnormal white matter lesions that may correspond to neurovascular lesions known neuropathologically. They do not appear to be directly related to schizophrenialike symptoms.
View details for Web of Science ID A1996TP96800017
View details for PubMedID 8770257
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Neuroimaging and the cognitive neuroscience of schizophrenia
SCHIZOPHRENIA BULLETIN
1996; 22 (4): 703-725
Abstract
The Carmel Workshop on Cognitive Psychophysiology began in 1980, and the focus of the 1996 workshop was on schizophrenia. Research into schizophrenia is in the midst of a period of unparalleled advance, driven in large part, by improvements in neuroimaging technology that make detailed examination of in vivo brain structure and function possible. Neuroimaging studies may help provide a bridge between investigations demonstrating molecular and cellular abnormalities in schizophrenia and those demonstrating cognitive dysfunction. The workshop brought together experts in different neuroimaging modalities to present the strengths and advantages of each, as well as the insights each modality might bring into normal and schizophrenic cognitition. It began with a series of tutorials to inform participants of the state of the art in various disciplines. It then broke into four panels, each given a very specific topic assignment related to neuroimaging and/or the cognitive neuroscience of schizophrenia. After 1 1/2 days of discussion, each panel reported its conclusions to the workshop. Group I presented cellular models of the pathophysiology of schizophrenia. Group II examined experimental paradigms for studying cognitive function and schizophrenia. Group III examined technical issues in image processing and combining data across different modalities. Group IV sought to survey the current state of knowledge about the pathophysiology of schizophrenia. The conclusions of each of the groups are presented in this report.
View details for Web of Science ID A1996VT40400013
View details for PubMedID 8938923
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Effects of cortical gray matter, attention, and schizophrenia on P300 amplitude
11th International Conference on Event-Related Potentials (EPIC XI)
ELSEVIER SCIENCE BV. 1996: 916–921
View details for Web of Science ID A1996BG27K00153
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LONGITUDINAL CHANGES IN MAGNETIC-RESONANCE-IMAGING BRAIN VOLUMES IN ABSTINENT AND RELAPSED ALCOHOLICS
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1995; 19 (5): 1177-1191
Abstract
Chronic alcoholism is associated with smaller volumes of cortical gray matter and white matter and a complementary increase in brain cerebrospinal fluid (CSF) volumes, relative to age norms. This longitudinal study quantified the extent of brain volume changes associated with abstinence and drinking at three time points in chronic alcoholics. We obtained magnetic resonance imaging (MRI) on 58 alcoholic men after an average of 12 days (MRI-1) and 32 days (MRI-2) of sobriety. In addition, 58 healthy control subjects were scanned at a comparable interval. At MRI-3, 11 controls and 39 alcoholics were rescanned, 2-12 months after MRI-2; 19 alcoholics had abstained, and 20 had resumed drinking. Axial MRI slices were segmented into cortical gray matter, white matter, and CSF and summed over seven slices; lateral and third ventricular volumes were also estimated. MRI volume changes were corrected using an estimate of interscan measurement error caused by head positioning differences, and then divided by the interval to yield rates of change (slopes). From MRI-1 to MRI-2, the alcoholic group showed declines in CSF volumes of the lateral ventricles and posterior cortical sulci, and a trend toward an increase in anterior cortical gray matter volume relative to the control group. From MRI-2 to MRI-3, third ventricular volumes decreased in the abstainers relative to the relapsers and controls; cortical white matter volume decreased in the relapsers. In the relapsers, lifetime consumption of alcohol (as of MRI-1) predicted later vulnerability to white matter volume decline and third ventricular enlargement with resumption of drinking. These data suggest that improvement in cortical gray matter, sulcal, and lateral ventricular volumes occur early in the course of abstinence, and that improvement in third ventricular volume appears later with continued abstinence.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1995TA73800014
View details for PubMedID 8561288
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SEMANTIC PRIMING IS DISRUPTED BY INTRUSIVE NOISES IN THE ELDERLY
WILEY-BLACKWELL PUBLISHING, INC. 1995: S32–S32
View details for Web of Science ID A1995RT16000128
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EVENT-RELATED POTENTIALS IN THE STUDY OF PSYCHIATRIC-DISORDERS
ARCHIVES OF GENERAL PSYCHIATRY
1995; 52 (7): 559-563
View details for Web of Science ID A1995RH81500004
View details for PubMedID 7598632
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AGE-RELATED DECLINE IN MRI VOLUMES OF TEMPORAL-LOBE GRAY-MATTER BUT NOT HIPPOCAMPUS
NEUROBIOLOGY OF AGING
1995; 16 (4): 591-606
Abstract
The effect of normal aging on the volume of the hippocampus and temporal cortex was assessed cross-sectionally with quantitative Magnetic Resonance Imaging (MRI) in 72 healthy men, spanning 5 decades of the adult age range (21 to 70 years). Neither the hippocampal nor cortical white matter volumes were significantly correlated with age. By contrast, left and right temporal lobe gray matter volumes, exclusive of the hippocampal measures, each decreased with age (p < 0.01). Volumes of temporal lobe sulcal CSF and the ventricular system (temporal horns and lateral and third ventricles) significantly increased with age. Measures of verbal and nonverbal working memory showed age-related declines and were related to enlargement of the three ventricular regions, which may be indicative of age-related atrophy of the adjacent cortex but not the hippocampus, at least up to age 70 years.
View details for Web of Science ID A1995RL48800012
View details for PubMedID 8544910
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BRAIN DYSMORPHOLOGY IN ADULTS WITH CONGENITAL-RUBELLA PLUS SCHIZOPHRENIALIKE SYMPTOMS
BIOLOGICAL PSYCHIATRY
1995; 37 (11): 764-776
Abstract
Brain morphology was quantified with magnetic resonance imaging (MRI) in adult patients with congenital rubella who also had schizophrenialike symptoms. MRIs were compared with those of adult early-onset schizophrenic patients without congenital rubella and age-matched healthy control subjects. The rubella patients had significantly smaller intracranial volumes and shorter stature than the schizophrenic patients or the controls; however, both patient groups had smaller cortical gray matter, but not white matter, volumes than the control group, even when the MRI volumes were corrected for head size and age. In addition, both patient groups showed significant enlargement of the lateral ventricles but not cortical sulci when compared with expected values of normal adults of the same age and head size. Overall, the pattern of dysmorphology was identical in the rubella and the schizophrenic groups. The observations in the rubella group are consistent with a developmental lesion that limits full brain growth, with the small intracranial volume due at least in part to a severe cortical gray matter volume deficit. Thus, the brain dysmorphology of congenital rubella may provide an instance of prenatal viral infection that models the schizophrenic pattern and provides indirect support for a developmental hypothesis of the neuropathogenesis of schizophrenia.
View details for Web of Science ID A1995RA24400002
View details for PubMedID 7647161
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GRAY-MATTER DEFICITS IN SCHIZOPHRENIA ALCOHOLISM COMORBIDITY
ELSEVIER SCIENCE INC. 1995: 629–29
View details for Web of Science ID A1995QX03700131
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LONGITUDINAL VOLUMETRIC COMPUTED TOMOGRAPHIC ANALYSIS OF REGIONAL BRAIN CHANGES IN NORMAL AGING AND ALZHEIMERS-DISEASE
ARCHIVES OF NEUROLOGY
1995; 52 (4): 392-402
Abstract
This study used a semiautomated image analysis technique to quantify the rate and regional pattern of cerebrospinal fluid (CSF) volume changes in the computed tomographic brain examinations of healthy adults and patients with Alzheimer's disease (AD).Longitudinal, within-subject design, with statistical correction for longitudinal method error (eg, head repositioning effects).Palo Alto (Calif) Department of Veterans Affairs Medical Center.The 41 patients with AD were recruited from the Geriatric Psychiatry Research Unit and the National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 35 healthy control subjects were recruited from the local community.Cerebrospinal fluid volumes estimated from computed tomographic scans.Even after accounting for an estimate of method error (eg, head positioning effects) across computed tomographic examinations, the patients with AD showed greater annual CSF volume increases than did the control group. This CSF volume enlargement was not uniform across brain regions of interest; rather, the patients with AD showed disproportionate volume increases in the ventricular system and the sylvian fissures. Greater CSF volume changes in the patients with AD were significantly associated with greater cognitive decline on the Mini-Mental State Examination. Furthermore, younger patients with AD showed more rapid progression on computed tomographic scans than did older patients.The rate of CSF volume enlargement is region specific, with the most marked annual rate of change occurring in the ventricular system and the sylvian fissures. In addition, younger patients show more rapid progression in the ventricular and frontal sulcal brain regions of interest than do older patients.
View details for Web of Science ID A1995QR98600014
View details for PubMedID 7710375
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EFFECTS OF SEROQUEL(TM) (ICI-204-636) ON PLATELET SEROTONIN-2 BINDING IN SCHIZOPHRENIA
ELSEVIER SCIENCE BV. 1995: 149–50
View details for Web of Science ID A1995QN95200440
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REGIONAL PROFILES OF CORTICAL GRAY-MATTER VOLUME DEFICITS IN SCHIZOPHRENIA AND ALCOHOLISM
ELSEVIER SCIENCE BV. 1995: 100–100
View details for Web of Science ID A1995QN95200287
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CORTICAL GRAY-MATTER VOLUME DEFICITS IN WOMEN WITH SCHIZOPHRENIA
ELSEVIER SCIENCE BV. 1995: 95–96
View details for Web of Science ID A1995QN95200273
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ANTERIOR HIPPOCAMPAL VOLUME DEFICITS IN NONAMNESIC, AGING CHRONIC-ALCOHOLICS
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1995; 19 (1): 110-122
Abstract
Magnetic resonance imaging was used to quantify the volume of the hippocampus in 47 men with chronic alcoholism and 72 healthy male control subjects. The subjects ranged in age from 21 to 70 years, thus permitting a test of whether older alcoholics suffer greater brain tissue volume reduction than do younger ones. Comparison brain regions included temporal lobe gray matter, white matter, and cerebrospinal fluid, as well as measures of the lateral ventricles, third ventricle, and temporal horns. The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group. Furthermore, the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics. Despite the hippocampal volume deficit, these alcoholics did not demonstrate an explicit memory impairment; furthermore, memory test scores did not correlate significantly with hippocampal volumes. In the alcoholics, the age-related volume loss, which was over and above that expected in normal aging, was also evident in the temporal cortex and white matter. Likewise, alcoholic ventricular enlargement was age-related. Analysis of covariance revealed that the anterior hippocampal deficit persisted after accounting for the temporal lobe gray matter volume deficit. Multiple regression analysis revealed that the age-related brain volume abnormalities observed in the alcoholics could not be attributed to duration of alcoholism or total lifetime consumption of alcohol.
View details for Web of Science ID A1995QG62500018
View details for PubMedID 7771636
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AUTOMATED MR SEGMENTATION METHOD CLARIFIED
AMERICAN JOURNAL OF NEURORADIOLOGY
1995; 16 (2): 406-406
View details for Web of Science ID A1995QG57400027
View details for PubMedID 7726091
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ELDERLY MEN AND WOMEN ARE LESS RESPONSIVE TO STARTLING NOISES - N1, P3 AND BLINK EVIDENCE
Annual Meeting of the Society-for-Psychophysiological-Research
ELSEVIER SCIENCE BV. 1995: 57–80
Abstract
Previously we observed that the P3 component of the event-related brain potential (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we tried to eliminate possible effects of age-related hearing deficits on the responses to noises by filtering them to include only frequencies heard best by the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz, 70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band noise set to approximately 65 dB SL). The order of the three sequences was counterbalanced across age and sex. Younger subjects blinked to the noise 4-5 times more often than older subjects and had N1 and P3 amplitudes that were 2-3 times larger, regardless of the noise type. N1 amplitude to the background frequent tones and non-startle blinks did not differ between groups. Thus, even when noises were narrow band and set relative to each subject's threshold, older subjects were less responsive to startling auditory stimuli than were younger.
View details for Web of Science ID A1995QE66900001
View details for PubMedID 7734630
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Structural brain alterations associated with alcoholism
ALCOHOL HEALTH & RESEARCH WORLD
1995; 19 (4): 266-272
View details for Web of Science ID A1995VN75300002
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STRUCTURAL BRAIN IMAGING IN SCHIZOPHRENIA
CLINICAL NEUROSCIENCE
1995; 3 (2): 105-111
Abstract
In vivo neuroimaging techniques have characterized the global features of brain dysmorphology in schizophrenia. These features include ventriculomegaly and widespread sulcal dilation, which particularly affect the frontal and temporal lobes and involve cortical gray matter rather than white matter. Dysmorphology of specific brain structures such as the basal ganglia and hippocampus, which have been implicated in the pathophysiology of schizophrenia by pharmacological manipulations and post mortem investigations, have not been consistently observed in vivo, perhaps because of differences in imaging and analysis techniques, methods used to control for variance due to age and head size, and sample characteristics. The epidemiology of the observed widespread brain dysmorphology supports a developmental origin, perhaps with limited progressive change beyond that expected in normal aging. Establishing the clinical significance of relatively static structural brain dysmorphologies remains a major challenge that may be best met by use of combined cross-sectional and longitudinal study designs.
View details for Web of Science ID A1995RL56800008
View details for PubMedID 7583616
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Structural Brain Alterations Associated With Alcoholism.
Alcohol health and research world
1995; 19 (4): 266-272
Abstract
Structural changes in the brains of chronic heavy drinkers that were first observed in pathological studies have been supported and expanded upon using computed tomography (CT) and magnetic resonance imaging (MRI) techniques. In general, the volume of brain tissue appears decreased in chronic drinkers, and this finding may be affected by a person's age, gender, and other factors. MRI studies also demonstrate some increase in brain tissue volume after a chronic drinker has been abstinent for a period of months. Whether this tissue increase can be linked with recovery of brain functioning remains unanswered.
View details for PubMedID 31798032
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Alcohol and the Cerebellum: Effects on Balance, Motor Coordination, and Cognition.
Alcohol health and research world
1995; 19 (2): 138-141
Abstract
Alcoholics often suffer from motor incoordination resulting from alcohol-related cerebellar damage. However, the effect of cerebellar structural damage on cognitive functioning has not been clearly demonstrated. It is not known if the relationships observed between cerebellar damage and functional impairments persist with abstinence from alcohol. Cell death may cause permanent loss of function, whereas tissue shrinkage without permanent cell loss might represent the potential for recovery. This article examines research on the interrelationship of alcohol-related abnormalities in cerebellar structure and function. Research such as this may provide knowledge to guide future rehabilitation efforts.
View details for PubMedID 31798074
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NEOCORTICAL GRAY-MATTER DEFICITS IN PATIENTS WITH EPILEPSY AND SCHIZOPHRENIA-LIKE SYNDROMES
WILEY-BLACKWELL PUBLISHING, INC. 1995: 681–681
View details for Web of Science ID A1995TD34700676
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ALCOHOL AND THE CEREBELLUM - EFFECTS ON BALANCE, MOTOR COORDINATION, AND COGNITION
ALCOHOL HEALTH & RESEARCH WORLD
1995; 19 (2): 138-141
View details for Web of Science ID A1995TH28000008
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A DEFICIT PROFILE OF EXECUTIVE, MEMORY, AND MOTOR FUNCTIONS IN SCHIZOPHRENIA
BIOLOGICAL PSYCHIATRY
1994; 36 (10): 641-653
Abstract
This study examined the neuropsychological deficits associated with schizophrenia and the interrelationships among multiple dissociable cognitive and motor functions. The tests were selected for their previously demonstrated sensitivity to circumscribed brain pathology and included four functional domains: executive functions, short-term memory and production, motor ability, and declarative memory. Each test composite was divided according to verbal versus nonverbal material or left- versus right-hand performance; this distinction permitted functions principally subserved by the left or right cerebral hemispheres to be tested separately. Data reduction was theoretically driven by the test selection and was achieved first by standardizing the scores of each test for age-related differences observed in the normal control group, and then by calculating test composite scores as an average of the age-corrected Z-scores of the tests comprising a functional composite. The schizophrenic group was impaired equivalently on all composites for both cerebral hemispheres; on average, the Z-scores of the patients were 1 standard deviation below those of the control group. The cognitive test composite scores were highly intercorrelated but showed only weak associations with motor ability. Multiple regression analyses suggested that symptom severity was a significant predictor of the Declarative Memory and Short-Term Memory/Production composite scores after accounting for disease duration, whereas disease duration uniquely contributed to the Executive Functions composite scores after controlling for symptom severity. Even though the schizophrenics as a group showed an equivalent level of deficit across all test composites, 1) the deficits were associated with different aspects of psychiatric symptomatology, 2) the motor deficit was independent of the cognitive deficits, and 3) each neuropsychological domain contributed independently to the deficit pattern. Thus, what appears to be a generalized functional deficit in schizophrenia may actually be, at least in part, combinations of multiple specific deficits.
View details for Web of Science ID A1994PT24700001
View details for PubMedID 7661935
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EFFECTS OF RACLOPRIDE TREATMENT ON PLASMA AND CSF HVA - RELATIONSHIPS WITH CLINICAL IMPROVEMENT IN MALE-SCHIZOPHRENICS
PSYCHOPHARMACOLOGY
1994; 116 (3): 291-296
Abstract
Thirty-two acutely psychotic, male schizophrenic patients received raclopride, at 2, 6, or 12 mg/day, or haloperidol, 15 mg/day for 4 weeks after randomized, double-blind assignment. Twenty-six patients, including 19 who had been assigned one of the three doses of raclopride, completed the study. Raclopride, particularly at 12 mg/day, increased CSF homovanillic acid (HVA) at 4 weeks, and plasma HVA at 2 days, of treatment. The clinical response to raclopride was significantly correlated with plasma raclopride concentrations and baseline plasma HVA concentrations. Although raclopride is a substituted benzamide with atypical properties in animals, these results suggest that the doses of raclopride required for clinical efficacy and elevation of clinical indices of brain dopamine turnover are similar.
View details for Web of Science ID A1994PR72500008
View details for PubMedID 7534423
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A QUANTITATIVE MAGNETIC-RESONANCE-IMAGING STUDY OF CHANGES IN BRAIN MORPHOLOGY FROM INFANCY TO LATE ADULTHOOD
ARCHIVES OF NEUROLOGY
1994; 51 (9): 874-887
Abstract
To model in vivo the dynamic interrelations of head size, gray matter, white matter, and cerebrospinal fluid (CSF) volumes from infancy to old age using magnetic resonance imaging (MRI).Cross-sectional, between-subjects using an age-regression model.A Veterans Affairs medical center and community hospitals.There were 88 male and female subjects aged 3 months to 30 years whose clinical MRI film had been read as normal and 73 healthy male volunteers aged 21 to 70 years who had an MRI performed specifically for this study.These MRI data were quantified using a semiautomated computer technique for segmenting images into gray matter, white matter, and CSF compartments. The cortex was defined geometrically as the outer 45% on each analyzed slice, and the volumes of cortical white matter, gray matter, and CSF were computed. Subcortical (ventricular) CSF volume was computed for the inner 55% of each analyzed slice.In the younger sample, intracranial volume increased by about 300 mL from 3 months to 10 years. The same patterns of change in volume of each compartment across the age range were seen in both sexes: cortical gray matter volume peaked around age 4 years and decreased thereafter; cortical white matter volume increased steadily until about age 20 years; cortical and ventricular CSF volumes remained constant. In the older sample, brain volumes were statistically adjusted for normal variation in head size through a regression procedure and revealed the following pattern: cortical gray matter volume decreased curvilin-early, showing an average volume loss of 0.7 mL/y, while cortical white matter volume remained constant during the five decades; complementary to the cortical gray matter decrease, cortical CSF volume increased by 0.6 mL/y and ventricular volumes increased by 0.3 mL/y.These patterns of growth and change seen in vivo with MRI are largely consistent with neuropathological studies, as well as animal models of development, and may reflect neuronal progressive and regressive processes, including cell growth, myelination, cell death, and atrophy.
View details for Web of Science ID A1994PG22500008
View details for PubMedID 8080387
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ERPS IN SCHIZOPHRENIA - EFFECTS OF ANTIPSYCHOTIC MEDICATION
BIOLOGICAL PSYCHIATRY
1994; 36 (3): 153-170
Abstract
Thirty unmedicated schizophrenics were compared to 29 age-matched controls on auditory and visual event-related brain potential (ERP) paradigms. Twenty-one of these patients were tested again after 1 week on placebo and after 4 weeks on antipsychotic medication. Before treatment, N1, N2, and P3 components of the auditory ERP were smaller in the schizophrenics than in the controls. Although visual N2 was smaller in schizophrenics, visual P3 was not. In spite of significant clinical improvement with antipsychotic treatment, amplitudes of auditory and visual N1, N2, and P3 were not significantly changed. Higher blood levels of antipsychotic medication were related to reductions in auditory P3 latency, however. In addition, higher levels of cerebrospinal fluid (CSF) MHPG (methoxyhydroxyphenylglycol) were associated with larger auditory N1s and larger auditory and visual P3s, suggesting an influence of arousal on these components in schizophrenics. In spite of this influence, reduction of the auditory P3 in schizophrenia is an enduring trait of the disease, which is not affected by antipsychotic medication or clinical improvement.
View details for Web of Science ID A1994PB80100003
View details for PubMedID 7948453
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FUNCTIONAL CORRELATES OF GRAY-MATTER VOLUME DEFICITS IN SCHIZOPHRENIA
ELSEVIER SCIENCE INC. 1994: 719–19
View details for Web of Science ID A1994NJ17200373
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EFFECT OF CORTICAL GRAY-MATTER, ATTENTION AND SCHIZOPHRENIA ON P300 AMPLITUDE
ELSEVIER SCIENCE INC. 1994: 705–
View details for Web of Science ID A1994NJ17200323
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VOLUMETRIC MRI ASSESSMENT OF TEMPORAL-LOBE STRUCTURES IN SCHIZOPHRENIA
BIOLOGICAL PSYCHIATRY
1994; 35 (8): 501-516
Abstract
This magnetic resonance imaging (MRI) study was designed to investigate whether patients with schizophrenia have focal or lateralized deficits in the volumes of temporal lobe structures. Estimated volumes of the temporal lobes, hippocampi, superior temporal gyri, lateral ventricles, third ventricle, temporal horns of the lateral ventricles, and a frontal-parietal reference area (FPRA) were quantified for each hemisphere. The schizophrenic group had less gray matter (GM) in the temporal lobes and the FPRA relative to controls. Ventricular volumes were significantly larger in the schizophrenic group, as was cerebrospinal fluid (CSF) volume for temporal lobe sulci. No significant differences in hippocampal volumes emerged between groups. The magnitude of GM deficit was not greater in the temporal lobes relative to the FPRA. These results confirm the presence of bilateral GM volume deficits of the temporal lobes in schizophrenia but do not support the hypothesis that structural changes preferentially affect the temporal lobes or the left cerebral hemisphere.
View details for Web of Science ID A1994NJ34700001
View details for PubMedID 8038294
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THE RELATIONSHIP BETWEEN P300 AMPLITUDE AND REGIONAL GRAY-MATTER VOLUMES DEPENDS UPON THE ATTENTIONAL SYSTEM ENGAGED
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1994; 90 (3): 214-228
Abstract
Event-related potentials (ERPs) and brain magnetic resonance images (MRIs) were acquired from 28 normal men, age 21-60 years. ERPs were recorded during 3 paradigms designed to elicit automatic or effortful attention, and a combination of both. MRI-derived measures of brain gray matter, white matter and cerebral spinal fluid (CSF) volumes were computed from frontal, parietal and temporal lobes. P300 amplitude correlated significantly with gray matter volumes but not with white matter or CSF volumes. Furthermore, the relationships between P300 amplitude and gray matter volumes reflected functional rather than direct topographical relationships: P300 recorded at Pz during automatically elicited attention correlated significantly with frontal but not parietal lobe gray matter volumes, P300 recorded during effortful attention correlated significantly with parietal but not frontal lobe gray matter volumes, and P300 recorded when both types of attention were invoked correlated significantly with both frontal and parietal gray matter volumes. Startle blinks, also elicited during automatic attention-engaging paradigms, were significantly correlated with frontal but not parietal lobe gray matter volumes. There was no evidence for a direct spatial relationship between P300 amplitude and the gray matter volumes underlying the recording electrode.
View details for Web of Science ID A1994ND22100006
View details for PubMedID 7511503
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SCHIZOPHRENICS HAVE FEWER AND SMALLER P300S - A SINGLE-TRIAL ANALYSIS
BIOLOGICAL PSYCHIATRY
1994; 35 (2): 96-103
Abstract
Because P300 is typically measured from an average of single trials, variations among individual trials may account for P300 amplitude reduction so often seen in patients with schizophrenia. We tested three hypotheses regarding single-trial contribution to small average P300s in schizophrenics: normal P300s are elicited on some trials and no P300s on others, all trials have consistently small P300s, or P300 latency varies over trials. Nineteen schizophrenics and 35 controls were tested on a two-tone auditory oddball event-related potential (ERP) paradigm. ERPs recorded from the parietal electrode (Pz) were subjected to a P300-screening procedure in which a 2 Hz half-sine wave template was moved across the electroencephalogram (EEG) to find the point of best fit. If, for the point of best fit, the EEG:Template covariance was greater in the signal epoch (280-600 msec) than in the noise epoch (610-930 msec), and if the EEG:Template correlation was statistically significant, the trial passed the P300-screen and was deemed to have a P300. Three types of average ERPs were constructed: Traditional Average from all good (artifact-free, correct response) trials, P300-Screen Average from all good trials that also passed the P300-screen, and Latency Adjusted Average by aligning the P300-screen trials at the latency of maximum covariance. Traditional average ERPs were significantly smaller in schizophrenics than in controls. The results of the P300-screen confirmed all three hypotheses: schizophrenics had fewer trials passing the P300-screen, smaller P300s on each trial, and P300s that were more variable in latency across trials.(ABSTRACT TRUNCATED AT 250 WORDS)
View details for Web of Science ID A1994MW69800003
View details for PubMedID 8167215
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INCREASE IN BRAIN CEREBROSPINAL-FLUID VOLUME IS GREATER IN OLDER THAN IN YOUNGER ALCOHOLIC PATIENTS - A REPLICATION STUDY AND CT/MRI COMPARISON
PSYCHIATRY RESEARCH-NEUROIMAGING
1993; 50 (4): 257-274
Abstract
This cross-sectional study used a semi-automated analysis technique to quantify regional brain cerebrospinal fluid (CSF) volumes derived from computed tomography (CT) in 84 healthy men ranging from 21 to 82 years of age and 28 patients meeting Research Diagnostic Criteria for alcohol dependence. The goals were to replicate an earlier CT study of an independent sample of alcoholic and control subjects (Pfefferbaum et al., 1988a; Zipursky et al., 1988) and to compare CT assessments of brain changes with magnetic resonance imaging (MRI) assessments made in the same alcoholic patients (Pfefferbaum et al., 1992). Regional brain changes associated with normal aging were derived by regression analysis, using CT data collected from the healthy control subjects. As in the earlier CT study and in the concurrent MRI study, ventricular and sulcal CSF volumes in alcoholic patients were greater than would be expected for their age. Furthermore, the present CT study replicated the previous CT and MRI findings of a positive relationship between age and CSF volume enlargement in alcoholic patients over and above the normal age-related increase in CSF volume, suggesting greater vulnerability of the aging brain to alcohol. Comparison of CT- and MRI-derived estimates of ventricular and cortical sulcal volume revealed high correlations (> 0.80). MRI and CT produced similar absolute ventricular volumes, while MRI produced larger sulcal volume estimates than did CT. The difference in sulcal volume estimate may be due to differences between CT and MRI in slice thickness and sensitivity to partial volume effects.
View details for Web of Science ID A1993MT42000004
View details for PubMedID 8177924
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MAGNETIC-RESONANCE SPECTROSCOPIC IMAGING OF ETHANOL IN THE HUMAN BRAIN - A FEASIBILITY STUDY
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1993; 17 (5): 1072-1077
Abstract
The in vivo distribution of ethanol in normal human brain following the consumption of a moderate amount of alcohol was measured using magnetic resonance spectroscopic imaging. Three subjects were studied, and the spatial distribution of brain ethanol, 60-min postingestion and measured at a spatial resolution of 1.5 cm, was found to be highly nonuniform with the relative ethanol signal in cerebral spinal fluid, gray matter, and white matter determined to be 1.00, 0.72, and 0.37, respectively. These spectroscopic imaging results indicate that whereas in vivo magnetic resonance studies of ethanol are feasible, quantitative studies of alcohol need to account carefully for the various tissue types within the observed volume.
View details for Web of Science ID A1993ME46800024
View details for PubMedID 8279668
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CORRECTION FOR HEAD SIZE IN BRAIN-IMAGING MEASUREMENTS
PSYCHIATRY RESEARCH-NEUROIMAGING
1993; 50 (2): 121-139
Abstract
Structural brain-imaging measurements based on computed tomography (CT) or magnetic resonance imaging (MRI) are often corrected or adjusted for normal variation in head size. Some methods of head-size correction, such as the ventricle-brain ratio (VBR), are based on taking the brain structure size as a proportion of the estimated head size, while other methods have used a regression model to obtain head-size residualized structure measures. Recently, head-size correction was shown to result in less reliable volumetric measures of brain structures (Arndt et al., 1991). In the present study, MRI was used to examine the effects of head-size correction on the interrater reliability of volumetric measures of gray matter, white matter, and cerebrospinal fluid. Four raters independently scored MRI brain images from 26 subjects, generating separate estimates of head size and region of interest (ROI) size. Two methods were used to correct MRI values for differences in head size, one based on proportions and the other based on linear regression. Results confirmed that head-size correction did produce measures with lower reliability; however, further analysis based on classical measurement theory showed that the lower reliability was attributable not only to increased measurement error variance, but also to reduced true score variance. Subsequent analyses of criterion validity compared the raw (uncorrected) and head-size-corrected ROI measures in terms of their correlations with age in a sample of 43 normal control subjects, and in terms of their ability to differentiate schizophrenic patients (n = 22) from normal control subjects (n = 20). Results indicated that head-size correction often improved criterion validity, producing higher correlations with age and with diagnostic status than those produced by the raw measures. These findings suggest that head-size correction removes irrelevant true-score variance which reduces reliability yet improves the correlations with validity criteria such as age and diagnostic status.
View details for Web of Science ID A1993LK62400006
View details for PubMedID 8378488
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GREATER ABNORMALITIES OF BRAIN CEREBROSPINAL-FLUID VOLUMES IN YOUNGER THAN IN OLDER PATIENTS WITH ALZHEIMERS-DISEASE
ARCHIVES OF NEUROLOGY
1993; 50 (4): 359-373
Abstract
This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD).Cross-sectional, between-subject design, using an age-regression model.Palo Alto (Calif) Department of Veterans Affairs Medical Center.The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community.Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores.The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance.This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.
View details for Web of Science ID A1993KV70200007
View details for PubMedID 8460957
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FACTORS OF THE WISCONSIN CARD SORTING TEST AS MEASURES OF FRONTAL-LOBE FUNCTION IN SCHIZOPHRENIA AND IN CHRONIC-ALCOHOLISM
PSYCHIATRY RESEARCH
1993; 46 (2): 175-199
Abstract
The purpose of this study was to examine the factor structure of the Wisconsin Card Sorting Test (WCST). The scores of 22 patients with schizophrenia, 20 patients with chronic alcoholism, and 16 normal control subjects were entered into a principal components analysis, which yielded three factors: Perseveration, Inefficient Sorting, and Nonperseverative Errors. WCST performance of seven patients with lesions invading the dorsolateral prefrontal cortex, available from another study, provided criterion validity for the Perseveration factor and, less strongly, for the Inefficient Sorting factor. Two patterns of performance characterized the three patient groups: the schizophrenic group and frontal lobe group had the highest Perseveration factor scores, whereas the alcoholic group had the highest Inefficient Sorting scores; the Nonperseverative Errors factor showed no significant group differences. Construct validity of these factors involved assessing, in all but the frontal group, the degree of overlap (convergent validity) and separation (discriminant validity) of each WCST factor with scores from tests of other cognitive functions. The convergent and discriminant validity of the Perseveration factor, but not the remaining two factors, received support only within the group of schizophrenic patients.
View details for Web of Science ID A1993KU96900007
View details for PubMedID 8483976
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ABNORMALITIES OF THE LEFT TEMPORAL-LOBE IN SCHIZOPHRENIA
NEW ENGLAND JOURNAL OF MEDICINE
1992; 327 (23): 1689-1689
View details for Web of Science ID A1992KA26000031
View details for PubMedID 1435914
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BRAIN GRAY AND WHITE MATTER VOLUME LOSS ACCELERATES WITH AGING IN CHRONIC-ALCOHOLICS - A QUANTITATIVE MRI STUDY
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1992; 16 (6): 1078-1089
Abstract
Magnetic resonance imaging (MRI) was used to study in vivo the brains of 49 patients with chronic alcoholism, 3 to 4 weeks post-withdrawal, and 43 normal healthy controls, all right-handed male veterans between the ages of 23 and 70 years. MRI scans were analyzed using a semi-automated procedure, which allowed the subcortical regions to be segmented into cerebrospinal fluid (CSF) and brain tissue and the cortical regions to be segmented into CSF, gray matter, and white matter. An age regression model was used to examine the effects of alcohol on brain structure, over and above that expected from the normal aging process. The alcoholics exhibited decreased tissue and increased CSF after correcting for aging. In the cortex, there was significant loss of both gray matter and white matter volume. In this sample of alcoholics, no particular cortical region was preferentially affected or spared. Furthermore, brain tissue volume loss increased with advanced age in the alcoholics. In this group of alcoholics there was no relationship between length of illness and age, i.e., the younger alcoholics had as heavy alcohol use histories as did the older alcoholics. Thus, the increased brain tissue loss with advanced age is interpreted as evidence for age-related increase in brain vulnerability to chronic alcohol abuse.
View details for Web of Science ID A1992KD40900012
View details for PubMedID 1471762
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THE CONTRIBUTION OF CONSTRUCTIONAL ACCURACY AND ORGANIZATIONAL STRATEGY TO NONVERBAL RECALL IN SCHIZOPHRENIA AND CHRONIC-ALCOHOLISM
BIOLOGICAL PSYCHIATRY
1992; 32 (4): 312-333
Abstract
The Rey-Osterrieth complex figure was used to assess the separate influences of the constructional accuracy and the organizational strategy employed while copying the figure on the later, incidental recall of the figure. We tested a model, which hypothesized that subjects who copied the main framework of the figure holistically would be more likely to achieve good copy accuracy scores and to reproduce the figure more accurately at recall than subjects who used a piecemeal approach during copy. Subjects included 68 detoxified, chronic alcoholics (ALC), 28 patients with schizophrenia (SZ), and 69 normal control subjects (NCS). The results showed that the ALC and the SZ groups, on average, had lower accuracy and strategy scores at copy than did the NCS group, and furthermore, that the combined contributions of copy accuracy and copy strategy accounted for group differences at recall. A path analysis revealed that, for all three groups, copy strategy had a significant direct effect on copy accuracy. Moreover, copy accuracy and copy strategy made independent contributions to recall accuracy within the ALC and NCS groups; by contrast, within the SZ group, copy strategy made an independent contribution to recall performance but copy accuracy did not. These results suggest that (1) organizational strategy can influence constructional accuracy at both copy and recall; (2) copy accuracy and strategy have the potential to influence recall independently; and (3) the recall deficit in ALC could be attributed to abnormalities in both accuracy and strategy at copy, whereas in SZ it could be attributed only to strategy abnormalities. The deficits observed on the complex figure test in the ALC and SZ were primarily nonmnemonic and were related to ability in figure construction and organizational strategy.
View details for Web of Science ID A1992JW49300003
View details for PubMedID 1420646
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P3 AND SCHIZOPHRENIA
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
1992; 658: 146-162
View details for Web of Science ID A1992JL81200010
View details for PubMedID 1353949
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WIDESPREAD CEREBRAL GRAY-MATTER VOLUME DEFICITS IN SCHIZOPHRENIA
ARCHIVES OF GENERAL PSYCHIATRY
1992; 49 (3): 195-205
Abstract
Magnetic resonance imaging was used to investigate whether the structural brain differences commonly observed in patients with schizophrenia as compared with normal control subjects are specific to gray or white matter, and furthermore whether such abnormalities are localizable to circumscribed cortical regions. Accordingly, 22 patients meeting DSM-III-R criteria for schizophrenia and 20 healthy community volunteers, all 23 to 45 years old, received magnetic resonance imaging scans. Seven axial magnetic resonance imaging sections of 5-mm thickness were segmented into cerebrospinal fluid, gray matter, and white matter compartments and used for volumetric quantification. For the healthy control subjects, age correlated significantly with the percentage of all magnetic resonance imaging sections taken up by gray matter but not white matter. After correcting for the normal effect of age, the schizophrenic group was found to have significantly less gray matter than the control group but no difference in white matter; ventricular volume was 34% greater in the schizophrenic group. The schizophrenic group had less gray matter in all six cortical subregions analyzed; these differences attained statistical significance for all but the parietal measure. These findings have implications for studies of localized gray matter abnormalities and suggest that regional brain volume measurements need to be expressed in the context of possible widespread gray matter volume deficits in schizophrenia.
View details for Web of Science ID A1992HG92500003
View details for PubMedID 1567274
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DECREASED GRAY-MATTER IN NORMAL AGING - AN INVIVO MAGNETIC-RESONANCE STUDY
JOURNALS OF GERONTOLOGY
1992; 47 (1): B26-B30
Abstract
Using in vivo magnetic resonance (MR) images, the percentages of gray matter, white matter, and cerebrospinal fluid (CSF) in the brains of 8 young and 6 elderly normal male community volunteers were quantified. Compared with the young men, the elderly men had a significantly lower percentage of gray matter (p less than .01) and higher percentage of CSF (p less than .01). The percentage of white matter was not significantly different between the two groups. This finding suggests that the age-related decrease in brain tissue is chiefly due to loss of gray matter.
View details for Web of Science ID A1992GY68000010
View details for PubMedID 1730845
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EVENT-RELATED POTENTIALS IN ALCOHOLIC MEN - P3-AMPLITUDE REFLECTS FAMILY HISTORY BUT NOT ALCOHOL-CONSUMPTION
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1991; 15 (5): 839-850
Abstract
Multilead event-related potentials (ERPs), elicited by auditory and visual stimuli requiring a button press response and by a startling noise requiring no response, were recorded from male alcoholics and age-matched male controls (26-60 years old). Single-trial analyses of blink responses to the startling stimuli indicated that alcoholics startle less frequently but with equivalent amplitude as the controls. In contrast, single-trial analyses of P3 indicated that alcoholics generate a P3 as often as controls, but that their individual P3s are smaller. Alcoholics who reported a positive family history of problem drinking had larger startle blink amplitudes and smaller auditory and visual P3s than did alcoholics who reported a negative family history. Hierarchical regression analysis was used to demonstrate that smaller P3s in family history positive alcoholics were independent of lifetime alcohol consumption.
View details for Web of Science ID A1991GL40900018
View details for PubMedID 1755518
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NEUROPSYCHOLOGICAL DEFICITS ACCOMPANYING STRIATONIGRAL DEGENERATION
JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY
1991; 13 (5): 773-788
Abstract
This study presents a structural and functional description of a case of striatonigral degeneration (SND) and emphasizes neuropsychological findings. The patient, a 55-year-old woman with progressive and relatively intractable rigidity and bradykinesia, particularly of the right side, was studied with brain MR scans and with a wide variety of sensory, motor, and cognitive tests known to be subserved by specific brain regions. T2-weighted MR images revealed curvilinear areas of high signal in the lateral putamen at low magnetic field strength (0.3T) and adjacent regions of marked low signal in the posterior-lateral putamen at high magnetic field (1.5T). High signal changes in the insular cortex were also noted on the high field images. Letter fluency and short-term memory as well as motor speed, strength, and sequencing were selectively impaired. Taken together, the data of this case suggest that structural involvement of the putamen resulted in dysfunctions usually associated with the primary motor cortex and orbitofrontal cortex, while sparing functions of other frontal regions as well as temporal and parietal cortices.
View details for Web of Science ID A1991GK47600011
View details for PubMedID 1955531
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EVENT-RELATED POTENTIALS AND EYEBLINK RESPONSES IN AUTOMATIC AND CONTROLLED PROCESSING - EFFECTS OF AGE
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1991; 78 (5): 361-377
Abstract
Seventeen young (mean age = 20.2 years old) and 16 elderly (mean age = 72.6 years old) women were tested with event-related potential (ERP) paradigms designed to elicit responses in reaction time tasks and to a startling noise burst. EEG was analyzed from 17 standard 10-20 electrode sites. Reaction time and performance data suggested that the elderly did not perform worse than the young. Nevertheless, the physiological responses of the elderly differed significantly from those of the young. While the task-dependent P3s at Pz were smaller in the elderly than in the young, the automatic P3 was smaller yet. The distribution of both types of P3 across the scalp was more uniform in the elderly than in the young. Single-trial analyses revealed that the P3 amplitude differences at Pz were not due to latency dispersal of single trials. Single-trial startle eye blink responses to intense noise bursts during the automatic paradigm were considerably less frequent in the elderly, although their individual startle blinks were actually larger. The data demonstrate that the electrophysiological responses of the elderly are different from the young both in tasks eliciting automatic responses and in tasks requiring controlled processing.
View details for Web of Science ID A1991FL58200005
View details for PubMedID 1711455
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AUDITORY EVENT-RELATED POTENTIALS AND ELECTRODERMAL ACTIVITY IN MEDICATED AND UNMEDICATED SCHIZOPHRENICS
BIOLOGICAL PSYCHIATRY
1991; 29 (6): 585-599
Abstract
Event-related potentials (ERPs) and electrodermal activity were studied in 14 medicated schizophrenics, 17 unmedicated schizophrenics, and 23 age- and education-matched controls. Subjects were run in three auditory stimulus paradigms differing from the usual ERP paradigms in having interstimulus intervals greater than 12 sec to permit measurement of the longer latency skin conductance response (SCR). In every paradigm medicated but not unmedicated schizophrenics had smaller N120 amplitudes and fewer SCRs than controls. In addition, medicated schizophrenics showed reduced P200 amplitude and latency, longer P320 latency, and reduced skin conductance levels in certain paradigms. These effects cannot easily be attributed to different mental states of medicated and unmedicated patients, since their Brief Psychiatric Rating Scale scores were almost the same. It is more probable that antipsychotic and antiparkinsonian drugs reduced electrodermal activity through anticholinergic mechanisms and that the antipsychotic drugs attenuated N120 through other biological mechanisms.
View details for Web of Science ID A1991FG08800007
View details for PubMedID 1675890
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NEUROIMAGING STUDIES OF SCHIZOPHRENIA
SCHIZOPHRENIA RESEARCH
1991; 4 (2): 193-208
Abstract
Neuroimaging studies of schizophrenia have identified abnormalities in neuroanatomy, regional brain metabolism and receptor physiology. Computerized tomographic (CT) studies have demonstrated gross ventricular and sulcal enlargement. These findings are probably nonprogressive, and it is not yet clear whether they are present only in a subgroup of patients; whether they represent a reduction in tissue from a previously normal condition or an abnormality in brain development; and what relationship they have to genetic risk for schizophrenia, clinical features, or longterm prognosis. Magnetic resonance imaging (MRI) studies, which offer higher resolution and greater flexibility in imaging plane, are currently focussing on specific neuroanatomic sites, such as the limbic system, basal ganglia and frontal cortex, implicated by neuropathological or clinical studies in the pathophysiology of schizophrenia. Positron emission tomographic (PET) scanning now enables investigators to study brain metabolism and receptor physiology. Evidence to date suggests that there may be significant abnormalities in the pattern of cerebral glucose utilization as well as in the density of dopamine receptors in patients with schizophrenia. Much future work is needed to determine the sensitivity and specificity of these observations as well as the extent to which they are affected by changes in clinical state, attention and medication exposure.
View details for Web of Science ID A1991FA66100009
View details for PubMedID 2039761
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ERPS AND BRAIN STRUCTURE - RELATIONSHIPS ACROSS THE ADULT AGE SPAN IN ALCOHOLICS AND IN A PATIENT WITH HERPES-SIMPLEX ENCEPHALITIS
INTERNATIONAL CONF ON EVENT-RELATED POTENTIALS ( EPIC IX )
ELSEVIER IRELAND LTD. 1991: 342–354
View details for Web of Science ID A1991HB51400033
View details for PubMedID 1915027
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HEPATOBILIARY MR IMAGING - 1ST HUMAN-EXPERIENCE WITH MNDPDP
RADIOLOGY
1991; 178 (1): 79-82
Abstract
The first human MR imaging results for the hepatobiliary contrast agent manganese(II)N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (MnDPDP) are reported. MnDPDP is a paramagnetic contrast agent specific for hepatobiliary imaging. An imaging study was performed to investigate the presence of contrast enhancement or facilitated visualization of normal structures. Twelve healthy subjects receiving MnDPDP at doses of 3, 10, or 15 mumol/kg were imaged after injection for approximately 30 minutes at 1-5-minute intervals. Transaxial abdominal images were obtained at 1.5 T in a single breath-hold interval of 21 seconds with use of a spin-echo pulse sequence (repetition time = 150 msec, echo time = 20 msec). Liver parenchyma enhancement was observed 1 minute after injection and persisted for at least 30 minutes. Clearance into the gallbladder was visualized within 15 minutes. Enhancement was dose-dependent; a dose of 10 mumol/kg produced a 75%-100% signal enhancement of the liver at 10 minutes after injection.
View details for Web of Science ID A1991EP11700015
View details for PubMedID 1898539
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FILTER FREQUENCY IN P-3 EXPERIMENTS
BIOLOGICAL PSYCHIATRY
1990; 28 (12): 1070-1071
View details for Web of Science ID A1990EP89400012
View details for PubMedID 2289003
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A QUANTITATIVE-ANALYSIS OF CT AND COGNITIVE MEASURES IN NORMAL AGING AND ALZHEIMERS-DISEASE
PSYCHIATRY RESEARCH-NEUROIMAGING
1990; 35 (2): 115-136
Abstract
Patients with presumptive Alzheimer's disease (AD) and healthy community volunteers received computed tomographic (CT) brain scans and cognitive tests. The CT scans were quantitatively analyzed with a semiautomated thresholding technique to derive volumetric measures of cerebrospinal fluid (CSF)-to-tissue ratios in six regions of interest (ROIs): lateral ventricles; vertex sulci, frontal sulci, Sylvian fissures, parieto-occipital sulci, and third ventricle. Regression analysis was performed on CT data from 85 older volunteers (ages 51-82) to generate age norms for each ROI. Within this group, tissue loss, as measured by the % CSF in each ROI, was highly correlated with age, although each ROI showed different rates of change over age. For all ROIs, the AD group had significantly more tissue loss than expected in normal aging. In addition, AD patients with a presenescent onset (before age 65) tended to have greater vertex sulcal and frontal sulcal tissue reduction than AD patients with a senescent onset (age 65 or after). When regional tissue reduction, corrected for age, was correlated with cognitive test scores, two sets of double dissociations emerged within the AD group: large CT z scores (i.e., decreased tissue and increased CSF) of frontal sulci, but not of the third ventricle, correlated with low Comprehension and Boston Naming Test scores, whereas large CT z scores of the third ventricle, but not of the frontal sulci, correlated with low scores on Digit Symbol and Picture Arrangement. These results suggest that heterogeneity of structural and functional integrity exists among patients with AD.
View details for Web of Science ID A1990EU28600003
View details for PubMedID 2100804
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MODEL ESTIMATES OF CSF AND SKULL INFLUENCES ON SCALP-RECORDED ERPS
SPECIAL PANEL ON ALCOHOL AND BRAIN FUNCTION
ELSEVIER SCIENCE INC. 1990: 479–82
Abstract
Dipole source localization promises to enhance knowledge about the structural and functional processes underlying differences in scalp-recorded ERPs observed between normal and patient populations. In this paper the Cuffin and Cohen (1) four-compartment model of volume conduction is used to examine the effects of variations in size of different compartments on scalp-recorded potentials. Using single discrete current dipoles located various distances from the center of the head, the effect of varying the thickness of the superficial extra-sulcal subarachnoid layer of CSF and the thickness of the skull are examined. Changing the thickness of the CSF layer alters amplitude recorded at the scalp and also alters the topographic distribution of the potential; these effects are more pronounced the closer the dipole source is to the surface. Changes in skull thickness have similar, but even greater effects.
View details for Web of Science ID A1990DX05900018
View details for PubMedID 2222852
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CLINICAL UTILITY OF LONG LATENCY COGNITIVE EVENT-RELATED POTENTIALS (P3) - THE CONS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1990; 76 (1): 6-12
View details for Web of Science ID A1990DQ19400003
View details for PubMedID 1694485
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INVIVO QUANTIFICATION OF THE LIMBIC SYSTEM USING MRI - EFFECTS OF NORMAL AGING
PSYCHIATRY RESEARCH-NEUROIMAGING
1990; 35 (1): 15-26
Abstract
Limbic system structures are of central interest in many neuropsychiatric disorders. Magnetic resonance imaging (MRI) has a unique potential for imaging limbic system structures in vivo, but methodological constraints can limit the usefulness and interpretation of the collected image data. In this article, we present approaches for the acquisition and quantification of high resolution MR images of the limbic system. We used a long TR, cardiac gated, flow compensated, spin echo sequence to collect 22, 3-mm thick contiguous sections encompassing the limbic system. The sections were oriented relative to standard internal neuroanatomical landmarks. The sequence provided good gray matter/white matter/cerebrospinal fluid (CSF) and CSF/bone contrast; the latter is necessary for quantifying intracranial size and total CSF volume. Using operationalized criteria, we achieved high interrater reliability in volumetric measurement of temporal horn and hippocampus. This technique was then used to examine the effect of normal aging by comparing eight young (mean = 24 years) and seven old (mean = 73 years) healthy community members. We were able to demonstrate a significant age-related increase in temporal horn volume and a trend toward an age-related decrease in hippocampal volume.
View details for Web of Science ID A1990DT48100002
View details for PubMedID 2367609
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VOLUMETRIC ASSESSMENT OF CEREBRAL ASYMMETRY FROM CT SCANS
PSYCHIATRY RESEARCH-NEUROIMAGING
1990; 35 (1): 71-89
Abstract
The advent of computed tomography (CT) of the brain has facilitated the study of brain asymmetries in normal individuals and in patients with various diseases. A computerized volumetric approach to quantifying CT scan data is used to demonstrate that imperfect alignment of the subject's head in the CT scanner can be a major source of artifact in the assessment of cerebral asymmetry. An approach for estimating the extent of misalignment of the head in the scanner is described. This approach can be used to take variations in head alignment into account when studying cerebral asymmetries. When volumetric measures were used, left-handed subjects (n = 5) were found to have a significantly lower left/right ratio of total cerebral hemispheric tissue than right-handed subjects (n = 41). The amount of asymmetry in the lateral ventricles was found to depend on their total size. A method for controlling for the effect of size when measuring asymmetry of the lateral ventricles is described. In both right- and left-handed subjects, the left lateral ventricles were significantly larger than the right. A magnetic resonance (MR) scan was performed with standard alignment and with a deliberate 10 degrees misalignment, using a volunteer subject. These data are presented to demonstrate how artifactual cerebral asymmetries can be generated by head tilt and to test the quantification procedures developed.
View details for Web of Science ID A1990DT48100007
View details for PubMedID 2367612
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BRAIN MAGNETIC-RESONANCE-IMAGING - APPROACHES FOR INVESTIGATING SCHIZOPHRENIA
SCHIZOPHRENIA BULLETIN
1990; 16 (3): 453-476
Abstract
Magnetic resonance imaging (MRI) offers the potential for identifying, in vivo, specific brain abnormalities associated with schizophrenia. The detection of small morphological differences in areas such as the prefrontal cortex, limbic structures, and basal ganglia requires attention to a number of technical and methodological details. The effects of age, height, sex, head size, and overall tissue loss are of particular concern and are discussed. MRI acquisition and processing techniques for improving gray/white tissue contrast and image resolution are described, as are techniques for quantitative, volumetric measurement of localized regions of interest and specific brain structures as well as of the brain as a whole. Techniques for evaluating frontal lobes, temporal lobes, and basal ganglia integrity are reviewed, and recent observations on these brain regions in patients with schizophrenia are described.
View details for Web of Science ID A1990EL87100013
View details for PubMedID 2287935
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P-3 IN SCHIZOPHRENIA IS AFFECTED BY STIMULUS MODALITY, RESPONSE REQUIREMENTS, MEDICATION STATUS, AND NEGATIVE SYMPTOMS
ARCHIVES OF GENERAL PSYCHIATRY
1989; 46 (11): 1035-1044
Abstract
Eighteen schizophrenics who were not taking medication, 13 schizophrenics who were taking medication, and 37 age-matched controls were tested with event-related potential paradigms designed to elicit P3 response automatically or effortfully (ie, with a choice reaction time task). Electroencephalograms were recorded from the 19 standard 10-20 electrode sites. Compared with controls, both groups of schizophrenics had reduced P3 amplitudes for both effortful and automatic paradigms. P3 latencies were delayed relative to controls for the medication-taking schizophrenics in the effortful paradigms. Negative symptoms derived from the Brief Psychiatric Rating Scale within 1 week of event-related potential testing correlated negatively with both auditory and visual P3 amplitude in the subjects who were not taking medication. There was no evidence that P3 is smaller over left temporal electrode sites in schizophrenics, as has been reported by others. P3 amplitude reduction in schizophrenia is a robust psychobiological phenomenon that is present regardless of medication status or task demands.
View details for Web of Science ID A1989AY08200009
View details for PubMedID 2573328
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MRI STUDY OF BRAIN CHANGES WITH SHORT-TERM ABSTINENCE FROM ALCOHOL
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1989; 13 (5): 664-666
Abstract
Magnetic resonance brain scans were obtained from 10 chronic alcoholics within 2 weeks of alcohol withdrawal, and 19 to 28 days later. Age-matched control subjects were scanned at comparable intervals. At the initial scan, the alcoholics had larger lateral ventricles than the controls; at the second scan, their ventricles were significantly smaller than at the first scan. Among the controls, there was no mean change in the size of the lateral ventricles between the first and second scan. This study demonstrates reversibility in ventricular enlargement with short-term abstinence from alcohol. The role of rehydration in this process and the possibility of further changes with continued abstinence remain to be tested.
View details for Web of Science ID A1989AW39200013
View details for PubMedID 2688465
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SEGMENTATION OF MR BRAIN IMAGES INTO CEREBROSPINAL-FLUID SPACES, WHITE AND GRAY-MATTER
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
1989; 13 (4): 588-593
Abstract
An interactive computer method for quantifying CSF, white matter, and gray matter in magnetic resonance (MR) axial brain scans is presented. A stripping algorithm is used to remove the skull and scalp from each axial section. The images are then filtered to correct for radiofrequency inhomogeneity image artifacts. Late echo images are subtracted from or added to early echo images to enhance fluid/tissue and gray/white tissue contrast, respectively. Thresholds for fluid/tissue and gray/white separation are set interactively. A boundary pixel locking algorithm is used to handle ambiguities due to partial voluming between the fluid and tissue compartments. The MR brain scans from five healthy, young, normal men were obtained using a standard neuroanatomical reference technique. These data were processed and percentages computed for fluid, gray matter and white matter compartments. The gray/white ratios compare favorably with those determined in a published postmortem brain study.
View details for Web of Science ID A1989AG41700006
View details for PubMedID 2745775
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SEASONAL-CHANGES OF CSF MONOAMINE METABOLITES IN PSYCHIATRIC-PATIENTS - WHAT IS THE SOURCE
PSYCHIATRY RESEARCH
1988; 25 (3): 361-363
View details for Web of Science ID A1988Q372300012
View details for PubMedID 2460883
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OSCILLATORY POTENTIALS AS A MARKER FOR DOPAMINERGIC DISEASE
DOCUMENTA OPHTHALMOLOGICA
1988; 69 (3): 255-261
Abstract
In an effort to find electrophysiologic correlates of dopaminergic disease in man, we measured oscillatory potentials of the electroretinogram in normal and unmedicated schizophrenic subjects, and in rabbits given D1 agonist or antagonist drugs. We found highly reproducible oscillatory potentials in twelve male schizophrenics that were indistinguishable from those in nine male normal volunteers. We also found little electroretinographic difference among four rabbits given intramuscular injections of SKF 38393 (a D1 agonist) and four control animals injected with saline. However, four animals given SCH 23390 (a D1 antagonist) showed diminution of the b-wave and selective suppression of the second oscillatory potential. This effect was more prominent in oscillatory potentials generated by 5-Hz flicker than by a single flash. These rabbit data suggest that further efforts at finding clinical correlations may be worthwhile, possibly with trial of flicker oscillatory potentials, and they support the concept that different oscillatory potentials have different generators.
View details for Web of Science ID A1988P573500006
View details for PubMedID 3048944
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COMPUTED TOMOGRAPHIC EVIDENCE FOR GENERALIZED SULCAL AND VENTRICULAR ENLARGEMENT IN SCHIZOPHRENIA
ARCHIVES OF GENERAL PSYCHIATRY
1988; 45 (7): 633-640
Abstract
Quantification of ventricular and sulcal volumes from the computed tomographic (CT) scans of 45 schizophrenic patients and 57 normal controls was carried out using a semi-automated computerized approach. The sizes of all cerebrospinal fluid spaces measured were significantly related to age in the control population. An age regression model was used to compare patients and controls. Schizophrenics had slightly larger ventricles and considerably larger sulci than controls. Enlargement of the ventricles and sulci was not correlated with measures of negative symptoms or neuropsychological impairment. The CT scans of eight very ill chronically institutionalized schizophrenics were also analyzed. Their CT findings did not differ significantly from the larger group of schizophrenics studied. Our results show that the cerebral atrophy found in schizophrenia is diffuse in nature and does not relate clearly to measures of disease severity or chronicity.
View details for Web of Science ID A1988P224900004
View details for PubMedID 3382323
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EVENT-RELATED POTENTIALS TO BREAKS IN SEQUENCES OF ALTERNATING PITCHES OR INTERSTIMULUS INTERVALS
PSYCHOPHYSIOLOGY
1988; 25 (3): 262-268
View details for Web of Science ID A1988N733300002
View details for PubMedID 3406327
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EVENT-RELATED POTENTIALS TO TIME-DEVIANT AND PITCH-DEVIANT TONES
PSYCHOPHYSIOLOGY
1988; 25 (3): 249-261
View details for Web of Science ID A1988N733300001
View details for PubMedID 3406326
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BRAIN COMPUTERIZED-TOMOGRAPHY IN SUBTYPES OF SEVERE CHRONIC-SCHIZOPHRENIA
PSYCHOLOGICAL MEDICINE
1988; 18 (1): 73-77
Abstract
Computerized tomographic (CT) brain scans were obtained in severely ill, chronic schizophrenic patients hospitalized in a long-term in-patient facility of a Veterans Administration hospital, and compared to CT brain scans from an age, sex and education-matched normal control population. In contrast to results obtained in our previous studies with younger, less severely ill, chronic schizophrenic patients, the current study population exhibited significantly increased rankings of third ventricular size and of fronto-tempero-sylvian atrophy, compared to normal control subjects.
View details for Web of Science ID A1988M523700009
View details for PubMedID 3258997
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BRAIN CT CHANGES IN ALCOHOLICS - EFFECTS OF AGE AND ALCOHOL-CONSUMPTION
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
1988; 12 (1): 81-87
Abstract
A computerized tomographic (CT) brain scan and assessments of lifetime alcohol consumption, body size, and cognitive performance were performed in 37 male alcoholics, aged 26-62 years. Hematocrit and mean corpuscular volume (MCV) were also measured. CT data were analyzed using a semiautomated scoring system yielding measures of percentage of fluid at the ventricles and cortical sulci. Normative brain CT data from 57 community controls spanning the adult age range allowed Z-score assessment of deviation from age norms for each alcoholic. Across the entire group, alcoholics had significantly enlarged ventricles and sulci for their age. Enlargement at both sites correlated significantly with lifetime alcohol consumption. Sulcal enlargement in alcoholics was found across all ages. In contrast, ventricular enlargement was apparent only in older alcoholics and became increasingly exaggerated with age. Measures of body size, hematocrit, and MCV correlated with ventricular but not sulcal enlargement, suggesting that nutritional factors play a role in ventricular enlargement. Associations between neuropsychological performance and CT changes or alcohol consumption were less pronounced and at times counterintuitive. The findings support a modest dose-effect relationship between ethanol exposure and changes in brain morphology, and suggest that ventricles and sulci show a different time course of response. The role of nutritional status needs to be more closely investigated.
View details for Web of Science ID A1988M164500016
View details for PubMedID 3279864
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DIFFERING EFFECTS OF DURATION OF ILLNESS ON CT FINDINGS IN ALCOHOLISM AND SCHIZOPHRENIA
PSYCHOPHARMACOLOGY BULLETIN
1988; 24 (3): 495-500
View details for Web of Science ID A1988T061000043
View details for PubMedID 3153515
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ERPS TO STIMULI REQUIRING RESPONSE PRODUCTION AND INHIBITION - EFFECTS OF AGE, PROBABILITY AND VISUAL NOISE
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1988; 71 (1): 55-63
Abstract
Sixty-six normal adults ranging in age from 20 to 85 years were presented with stimuli containing explicit instructions to initiate or to inhibit a motor response (the words 'push' or 'wait'). In one task, the effect of stimulus probability was investigated by varying probability between 0.25 and 0.75 for both Go and No-go stimuli. In another task, the effect of visual noise was investigated by degrading the stimuli with ampersands on half of the trials. Regression analysis was used to examine the effects of age on P3 amplitude and latency for each stimulus type. The effects of stimulus variables on P3, independent of age, were examined by standardizing each subject's data to those expected for a 20 year old. P3 latency to all stimuli and RT to Go stimuli increased with age. The latency of P3s to No-go stimuli was less sensitive to age than Go stimuli. P3 amplitude at Cz and Pz (but not Fz) diminished with age. P3s to Go stimuli were maximal at Pz and earlier than P3s to No-go stimuli. P3s to No-go stimuli were maximal at Cz. These differences between Go and No-go stimuli remained true under visual noise and probability manipulations. Visual noise prolonged the latency of Go and No-go P3. Less probable Go and No-go stimuli elicited larger and later P3s than more probable stimuli. Decreasing the probability of the No-go stimulus enhanced its central distribution.
View details for Web of Science ID A1988L794200007
View details for PubMedID 2446846
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LATE EVENT-RELATED POTENTIAL CHANGES IN ALCOHOLICS
ALCOHOL
1987; 4 (4): 275-281
Abstract
The P3 component of the event-related potential (ERP) was recorded during a Go/No-Go task from 42 alcoholic subjects, abstinent for 11-63 days, and 66 normal adult volunteers. In two different tasks, ERPs were elicited by visually presented words which provided explicit response instructions to Go (PUSH) or No-Go (WAIT). In the Noise Task, half of both Go and No-Go stimuli were degraded with ampersands (&P&U&S&H&, &W&A&I&T&). In the Probability Task, the probability of the Go stimulus was 25% and No-Go 75% on one run and the proportion reversed on another run. For both tasks, the amplitude of alcoholics' P3 was smaller than that of controls to the Go but not to the No-Go stimulus. There was a similar, but less pronounced trend for P3 latency to be delayed in alcoholic subjects for the Go, but not No-Go stimuli for the Noise Task. The P3 changes in alcoholics are consistent with those seen in several disease states which produce cognitive impairment.
View details for Web of Science ID A1987J909400009
View details for PubMedID 3620096
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SKULL THICKNESS INFLUENCES P3 AMPLITUDE
PSYCHOPHARMACOLOGY BULLETIN
1987; 23 (3): 493-496
View details for Web of Science ID A1987L237200039
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Event-related potentials to deviations of pitch and of timing.
Electroencephalography and clinical neurophysiology. Supplement
1987; 40: 241-245
View details for PubMedID 3480129
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Electroretinographic assessment in schizophrenia.
Electroencephalography and clinical neurophysiology. Supplement
1987; 40: 746-751
View details for PubMedID 3480203
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APPARENT RESPONSE INCOMPATIBILITY EFFECTS ON P3 LATENCY DEPEND ON THE TASK
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1986; 64 (5): 424-437
Abstract
Ten young women were tested with an ERP paradigm that used the words 'left,' 'right,' 'LEFT,' 'RIGHT' as stimuli. The stimulus sequence was presented as several separate runs with varying response instructions. Subjects were instructed to respond according to the meaning of the stimulus in the (WORD task), to the case in which the stimulus was written (CASE task), or to both the case and meaning of the stimulus (CASE/WORD) task. In each task, half the trials called for a response that was incompatible with the stimulus. For the WORD task, compatible and incompatible trials were presented as separate blocks of trials. For all 3 tasks an additional stimulus sequence was presented in which the words were degraded with superimposed visual random noise. Reaction time (RT) in the CASE/WORD task was more than 100 msec later than in the other tasks. In the WORD and CASE/WORD tasks, RT was delayed more than 100 msec when the response was incompatible with the stimulus. Degrading the stimulus additionally delayed RT by about 100 msec. In the WORD and CASE tasks, error RTs were earlier than correct RTs. P3 latency was measured with a single-trial latency adjustment algorithm. P3 latency was delayed in the CASE/WORD task compared to the other 2 tasks. P3 was delayed by degrading the stimuli. Contrary to some previous reports, P3 was delayed by about 70 msec when incompatible responses were required, but only in the WORD task. Taken together with error and RT data, these P3 latency data are consistent with the notion that the task causes subjects to adopt different strategies and hence different types of processing (i.e., serial vs. parallel). Depending on the type of processing, P3 may appear to be affected by response incompatibility.
View details for Web of Science ID A1986E561700007
View details for PubMedID 2428593
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AUTONOMIC CHARACTERISTICS OF AGORAPHOBIA WITH PANIC ATTACKS
BIOLOGICAL PSYCHIATRY
1986; 21 (12): 1133-1154
Abstract
We compared electrodermal and heart rate measures of autonomic activation between patients meeting DSM-III criteria for agoraphobia with panic attacks and controls in terms of tonic level, reactivity to various types of stimuli, recovery, habituation, and spontaneous variability. The most striking differences between groups in the laboratory were higher tonic levels of skin conductance and heart rate among patients. Patients' heart rates were also tonically elevated in a test situation outside the laboratory. Certain measures of habituation and spontaneous variability also differed between groups, but there were only weak and inconsistent differences in reactivity to, or recovery from, stimuli with diverse qualities of novelty, startlingness, intensity, or phobicity. The elevated activation levels may be signs of a chronic state or may be phobic responses to the testing situations. A minority of patients failed to show these elevated levels.
View details for Web of Science ID A1986D850400004
View details for PubMedID 3756263
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COMPUTER-INTERACTIVE METHOD FOR QUANTIFYING CEREBROSPINAL-FLUID AND TISSUE IN BRAIN CT SCANS - EFFECTS OF AGING
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
1986; 10 (4): 571-578
Abstract
Presented here is a modification of a previously developed, computed, semiautomated system for quantifying the amount of CSF and tissue on brain CT scans. The technique automatically strips skull from brain and applies a two-dimensional high-pass filter to reduce spectral-shift artifact. The resultant images are presented along with the raw images, section by section, on a screen for fluid-tissue differentiation by a human scorer. This is accomplished by adjusting a one-bit display of the filtered image until a satisfactory separation threshold is found. Data can be summed within or across sections to provide measures of CSF volume in specific regions of interest such as the ventricles and sulci. A major advantage is the improved accuracy of sulcal measurement. This method has been applied to scans of 57 community volunteers, 20-84 years old. High correlations have been established between rankings performed by an experienced clinician and automated rankings (r = 0.88 with rankings based on ventricular size, and r = 0.83 with rankings based on sulcal size). Furthermore, significant correlations were found between computed measures of ventricular size and age and between sulcal widening and age.
View details for Web of Science ID A1986D210700004
View details for PubMedID 3734197
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Applications of cognitive ERPs in psychiatric patients.
Electroencephalography and clinical neurophysiology. Supplement
1986; 38: 419-438
View details for PubMedID 3466780
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FLUORODEOXYGLUCOSE-18 PET IN SCHIZOPHRENIA
PSYCHIATRY RESEARCH
1985; 16 (4): 317-329
Abstract
Six chronic schizophrenic patients and six age-matched controls were studied with 18fluorodeoxyglucose (18FDG) positron emission tomography (PET). All patients were scanned when they had been free of medication for at least 2 weeks. Comparisons were made between the groups on regional ratios of cortical 18FDG, with manual and automated measures. Only one of eight regions, the right temporal cortical region, showed a significant group difference, and this effect was not significant when adjustment was made for multiple comparisons. Secondary analyses suggest that ventricular enlargement and age may be associated with a relatively "hypofrontal" pattern of 18FDG.
View details for Web of Science ID A1985AYD8300006
View details for PubMedID 3878971
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ERPS TO RESPONSE PRODUCTION AND INHIBITION
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1985; 60 (5): 423-434
Abstract
Three experiments investigating the effects of response production and inhibition on the N2 and P3 components of the ERP are reported. In the first experiment, 12 young female volunteers were presented with the words "push' and "wait' (semantic stimuli). On a separate series of trials, they were presented with arbitrary symbols assigned the same meanings (symbolic stimuli). For each stimulus series half of the stimuli were degraded. To obtain an estimate of reliability of the data, each task was repeated. Data were collected from Fz, Cz and Pz electrode sites. The P3 amplitude had a parietal maximum when the stimuli instructed subjects to respond (Go). The P3 was equal at central and parietal sites when the stimuli instructed the subjects to withhold a response (No-Go). This topographic pattern was obtained for all stimulus manipulations, simple and degraded stimuli, words and symbols, and for the first and second runs. The N2 was a frontal maximum component that was larger to the No-Go than to the Go stimuli. This result was also robust to the manipulations. A second experiment investigated the dependency of these findings on an overt motor response. In this experiment, the symbolic and semantic stimulus series were each presented twice. The subjects counted the Go stimuli and did not count the No-Go stimuli for one presentation and pressed the reaction time button as in experiment 1 for the other presentation. While counting (compared to button pressing) delayed the N2 and P3 peaks, counting and pressing produced similar results, including the Go/No-Go P3 distribution effects. A third experiment investigated the sensitivity of these findings to the orientation of the symbols instructing the subjects to respond or withhold the response. Again the pattern of results was robust to this manipulation.
View details for Web of Science ID A1985AHE7000006
View details for PubMedID 2580694
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P300 AND LONG-TERM-MEMORY - LATENCY PREDICTS RECOGNITION PERFORMANCE
PSYCHOPHYSIOLOGY
1985; 22 (5): 497-507
View details for Web of Science ID A1985AQM7100001
View details for PubMedID 4048349
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CLINICAL-APPLICATION OF THE P3 COMPONENT OF EVENT-RELATED POTENTIALS .1. NORMAL AGING
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1984; 59 (2): 85-103
Abstract
Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1-1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators. The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm. There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.
View details for Web of Science ID A1984SN71300001
View details for PubMedID 6200311
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CLINICAL-APPLICATION OF THE P3-COMPONENT OF EVENT-RELATED POTENTIALS .2. DEMENTIA, DEPRESSION AND SCHIZOPHRENIA
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1984; 59 (2): 104-124
Abstract
Patients with dementia, schizophrenia and depression were tested with analogous auditory and visual event-related potential (ERP) paradigms designed to elicit a large P3. The patient groups were compared to age normative predictions derived from a large control sample for a number of ERP and behavioral variables. The results were similar for the auditory and visual paradigms. P3 latency was prolonged two or more S.D.s beyond that predicted by age for less than one-half of the demented patients. This latency prolongation was significant for the group as a whole but would result in too many false negatives if used diagnostically for individuals. Furthermore, increased P3 latency was not specific, as the schizophrenic patients also had later P3s. The amplitude of P3 was reduced in the demented patients, but it was also smaller in other patient groups. The only variable which distinguished the demented patients from both controls and from the other patients was the single trial P3 latency/RT correlation. The demented patients, as a group, had significantly lower P3 latency/RT correlations, but this effect also was not sensitive enough to be diagnostic for individuals. The data from these two paradigms suggest that the P3 amplitude and latency abnormalities observed reflect a common, rather than a diagnostically specific deficit. This study is in contrast to some others which report much more sensitivity and specificity in the use of P3 latency in the diagnosis of dementia. Differences in task demands, patient samples and ERP analysis techniques might explain some of the discrepancy.
View details for Web of Science ID A1984SN71300002
View details for PubMedID 6200305
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ERPS AND PSYCHOPATHOLOGY .1. BEHAVIORAL PROCESS ISSUES
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
1984; 425 (JUN): 496-522
Abstract
The clinical study of ERPs has an inherent defect--a self-selection of clinical populations that hampers equating of clinically defined groups on factors extraneous to the independent variables. Such ex post facto studies increase the likelihood of confounding variables in the interpretation of findings. Hence, the development of lawful relationships between clinical variables and ERPs is impeded and the fulfillment of description, explanation, prediction, and control in brain science is thwarted. Proper methodologies and theory development can increase the likelihood of establishing these lawful relationships. One methodology of potential value in the clinical application of ERPs, particularly in studies of aging, is that of divided attention. Two promising theoretical developments in the understanding of brain functioning and aging are the distraction-arousal hypothesis and the controlled-automatic attention model. The evaluation of ERPs in the study of brain-behavior relations in clinical populations might be facilitated by the differentiation of concurrent, predictive, content, and construct validities.
View details for Web of Science ID A1984TA47400054
View details for PubMedID 6588871
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P300 LATENCY IN CHRONIC-ALCOHOLICS AND DEPRESSED-PATIENTS - A PRELIMINARY-REPORT
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
1984; 425 (JUN): 585-591
View details for Web of Science ID A1984TA47400062
View details for PubMedID 6588878
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AGE-RELATED LOSS OF TRABECULAR BONE IN PREMENOPAUSAL WOMEN - A BIOPSY STUDY
CALCIFIED TISSUE INTERNATIONAL
1983; 35 (4-5): 406-409
Abstract
We measured the trabecular bone volume (TBV) of 62 iliac crest biopsies taken from women admitted to lymphoma protocols at Stanford University between 1970-1981. All subjects were active, cycling premenopausal women, with bone marrows that were negative for tumor. Disease status was stage III or less in 90% of the subjects. Trabecular bone volume was negatively correlated with age, and the annual predicted loss of bone was 0.14-0.18% TBV, or 0.7% of the original bone volume. In addition, there was a substantial range of normal TBV at any given age, evident even during adolescence. This study demonstrates that TBV is lost from iliac crest throughout adult life. The large spread in TBV indicates further that factors operating during adolescence or even earlier may have an important impact on skeletal mass.
View details for Web of Science ID A1983RA53800003
View details for PubMedID 6616313
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MANIPULATION OF P3 LATENCY - SPEED VS ACCURACY INSTRUCTIONS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1983; 55 (2): 188-197
Abstract
Twelve young female subjects were presented with a series of horizontal line-pairs of same or different length in a two-alternative, forced-choice RT task, with 60 of each type pair in each block of trials. In one block (Easy) lines differed by 30%, in another block (Difficult) lines differed by 7%. Subjects were first given 60 practice trials with the Easy discrimination and with the instruction that speed and accuracy should be emphasized equally. For the next block of trials, accuracy was emphasized with a monetary bonus for accurate performance. Finally, in the last block of trials, speed was emphasized with a monetary bonus for speedy performance. Additionally, a penalty was incurred for RTs that exceeded a criterion level based on each individual subject's performance. The order of Easy and Difficult discrimination blocks was maintained within a subject but balanced across subjects. From the latency-adjusted P3s recorded from Pz, we obtained P3 latencies, amplitudes and single-trial P3 latency/RT correlations. RT to correct and incorrect trials and error data were also collected. P3 was considerably larger during the Speed than Accuracy conditions. The single-trial P3 latency/RT correlation was higher in Speed than in Accuracy runs. RT was 235 msec faster and P3 was 40 msec earlier during the Speed than during the Accuracy runs. On the other hand, discrimination difficulty delayed P3 and RT about equally, 28 and 43 msec respectively. This pattern suggests that speed instructions and discrimination difficulty affect stimulus processing time and response production time differently.
View details for Web of Science ID A1983QB97500010
View details for PubMedID 6185317
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EVENT-RELATED POTENTIALS TO A CHANGE OF PACE IN A VISUAL SEQUENCE
PSYCHOPHYSIOLOGY
1982; 19 (2): 173-177
View details for Web of Science ID A1982ND79500007
View details for PubMedID 7071296
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CT MEASURES OF CEREBROSPINAL-FLUID VOLUME IN ALCOHOLICS AND NORMAL VOLUNTEERS
PSYCHIATRY RESEARCH
1982; 7 (1): 9-17
Abstract
Cranial computed tomography (CT) scans were obtained in 46 male chronic alcoholics and 31 normal male volunteers. Automated methods were used to estimate the cerebrospinal fluid (CSF) volume in various intracranial zones. Measures of the ventricular fluid volume, the volume of fluid in cortical areas on CT sections at the level of the ventricles, and the sulcal fluid volumes on two convexity sections were computed. The alcoholic group, excluding subjects with chronic liver disease, had significantly more fluid than the control group on all sulcal measures. The group difference on the ventricular measure fell short of significance. Within the alcoholic group, no significant correlation was found between the number of years of alcoholism and any fluid measure when normal age effects were taken into account. A striking degree of variability in the sulcal volumes was observed within the alcoholic group, with many subjects showing normal values while a large group showed markedly elevated values. Further studies will be necessary to determine the significance of these variations.
View details for Web of Science ID A1982PE56600002
View details for PubMedID 6957902
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EXPECTANCY FOR EVENTS IN OLD-AGE - STIMULUS SEQUENCE EFFECTS ON P300 AND REACTION-TIME
JOURNALS OF GERONTOLOGY
1982; 37 (6): 696-704
Abstract
Event-related brain potentials were collected from 10 young (M = 22 years) and 10 elderly (M = 77 years) women. Stimuli were random sequences of 1000- and 1500-Hz tone pips in a two alternative, forced choice, reaction time task. Trials were sorted and averaged according to the sequence of the preceding four tones: continuations of repetitions (AAAAA) and alternations (ABABA) and discontinuations of repetitions (BBBBA) and alternations (BABAA). For both groups the P300 component of the event-related brain elicited larger P300s than did discontinuations of alternations, an effect especially large for the elderly women. Mean reaction time did not differ between the two groups, although P300 latencies were significantly longer for the elderly group. Results are discussed in terms of age-related differences in response strategies and sensitivity of P300 latency to response strategy.
View details for Web of Science ID A1982PN59300010
View details for PubMedID 7130643
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EFFECTS OF PERCEPTUAL AND COGNITIVE DIFFICULTY ON P3 AND RT IN YOUNG AND OLD ADULTS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1982; 54 (3): 311-321
Abstract
Ten healthy old and 10 healthy young subjects each received a series of trials in a memory retrieval task similar to that devised by Sternberg (1967). On each trial the subject saw a memory set of 2 or 4 digits (set size) followed by a probe. The task was to indicate whether the probe was a positive or negative instance (response type) of the memory set for that trial. On half the trials, the probe digits were degraded by a mask of random dots (stimulus quality). For both young and old subjects, RT was later to probes following the larger set size, later to degraded probes, and later to negative probes. For the young subjects only, P3 latency was delayed by the same variables affecting RT although to a lesser degree. P3 latency in the elderly responded quite differently: it was unaffected by set size or response type. However, P3 was somewhat delayed by the degraded probes suggesting that the failure to reflect set size or ceiling effect in the elderly. The correlation between single-trial P3 latency and RT in the elderly is lower than in the young. The data are discussed in terms of age-related differences in the meaning of P3 latency.
View details for Web of Science ID A1982PH34000007
View details for PubMedID 6179758
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BRAIN-STEM POTENTIALS IN CHRONIC-ALCOHOLICS
SOC PSYCHOPHYSIOL RES. 1982: 583–84
View details for Web of Science ID A1982PE85700148
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DRUGS AND CRIMINAL ASSAULTS BY ADOLESCENTS - A REPLICATION STUDY
JOURNAL OF PSYCHOACTIVE DRUGS
1981; 13 (3): 277-287
View details for Web of Science ID A1981MU57700008
View details for PubMedID 6977630
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LITHIUM EFFECT ON PARATHYROID-HORMONE
AMERICAN JOURNAL OF PSYCHIATRY
1981; 138 (4): 489-492
Abstract
Lithium has been reported to raise serum calcium and lower serum phosphate concentrations and to increase urinary calcium excretion. Because these changes may be effects of parathyroid hormone (PTH), PTH was measured in 19 patients receiving lithium. PTH was significantly higher in these patients than in 150 normal subjects. For all patients serum calcium concentrations correlated significantly with serum lithium concentrations. These results indicate that lithium may cause biochemical hyperparathyroidism. Secondary hyperparathyroidism in certain patients with lithium nephrotoxicity is also possible.
View details for Web of Science ID A1981LJ25500015
View details for PubMedID 7212107
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RELATIONSHIP OF CEREBRAL VENTRICULAR SIZE TO ALCOHOLICS PERFORMANCE ON THE LURIA-NEBRASKA NEUROPSYCHOLOGICAL BATTERY
JOURNAL OF STUDIES ON ALCOHOL
1981; 42 (9): 749-756
View details for Web of Science ID A1981MS99100005
View details for PubMedID 7311534
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GROUP-THERAPY IN THE MANAGEMENT OF MANIC-DEPRESSIVE ILLNESS
AMERICAN JOURNAL OF PSYCHOTHERAPY
1981; 35 (2): 226-234
Abstract
Because patients with bipolar affective illness have generally been viewed as poor candidates for psychotherapy, many clinicians have relied on lithium prophylaxis as the major treatment modality. However, even with lithium prophylaxis many patients still relapse, often in settings providing little support for maintenance treatment. This report presents the results of a long-term therapy group composed exclusively of bipolar manic-depressive patients, many of whom had histories of poor adherence ot lithium maintenance. The group met weekly and was conducted with an interpersonal, interactional "here and now" format. Patients attended an average of 47 sessions. Members were initially somewhat aloof and remote and minimized their problems. Over the course of their participation, members became more open and began to discuss their concerns about their illness and lithium maintenance treatment; during this time they functioned much as members in any long-term psychotherapy group. In the two-year period prior to entering the group, patients averaged 16.8 weeks of hospitalization; in the subsequent two-year period they averaged 3.6 weeks of hospitalization. Groups of this kind may offer a simple, cost-effective adjunct to lithium maintenance treatment and may provide the advantages and opportunities of psychotherapy to a group of patients generally seen as resistant to such approaches.
View details for Web of Science ID A1981LU66700008
View details for PubMedID 7258419
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AUDITORY EVENT-RELATED POTENTIALS IN SCHIZOPHRENIA AND DEPRESSION
PSYCHIATRY RESEARCH
1981; 4 (2): 199-212
Abstract
Event-related potentials in two auditory target detection paradigms and two auditory paradigms without overt tasks were studied in 22 schizophrenic, 21 depressed, and 28 matched control subjects meeting Research Diagnostic Criteria. In the target detection paradigms, schizophrenics showed a pattern of reduced N120 amplitude and shorter P200 latency to frequently occurring tones, and reduced P300 and Slow Wave amplitude to infrequent target and nontarget tones. This pattern is consistent with impaired selective attention for stimuli. For depressed patients these variables were generally intermediate between those of schizophrenics and controls. In the other paradigms N120 latency was greater for schizophrenics, and P200 amplitude was less for depressed patients.
View details for Web of Science ID A1981LM54300009
View details for PubMedID 6939010
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RACIAL INTOLERANCE IN A CORRECTIONAL INSTITUTION - AN ECOLOGICAL VIEW
AMERICAN JOURNAL OF PSYCHIATRY
1981; 138 (8): 1057-1062
Abstract
To determine the significance of social factors in racial intolerance, the authors studied the relationship between relational behavior and ethnicity, group status and role, peer acceptance, and group cohesion in an adolescent correctional institution. Results portray three distinct patterns of adaptation. Hispanics (Chicanos) formed a highly cohesive group that required considerable conformity to group norms; policy was implemented by a leadership capable of relating well to all ethnic groups. Whites formed a disorganized and fragmented group, led by individuals who engaged in racially antagonistic behavior. The highly cohesive black group and their leadership were simultaneously in the forefront of both racial cooperation and racial conflict.
View details for Web of Science ID A1981MA30300008
View details for PubMedID 7258381
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MONITORING NORTRIPTYLINE PLASMA-CONCENTRATIONS
AMERICAN JOURNAL OF PSYCHIATRY
1980; 137 (4): 485-486
View details for Web of Science ID A1980JM40600018
View details for PubMedID 7361940
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EVENT-RELATED POTENTIALS IN SCHIZOPHRENICS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1980; 48 (2): 127-139
Abstract
Fifteen schizophrenics and 15 age-matched controls were compared on 3 auditory event-related potential (ERP) paradigms that elicited a variety of components. In one paradigm, tones were given at 0.75, 2.25 and 6.75 sec interstimulus intervals; in another, infrequently occurring targets in a reaction-time task were interspersed with frequent background stimuli; and, in a third, noise bursts or tones were delivered in a random sequence at either 70 or 100 dB SPL. The sensitivity of some of the ERP components in distinguishing schizophrenics from controls depended on the conditions under which the component was elicited. N1 amplitude was smaller in the schizophrenics than in the controls after longer interstimulus intervals. P2 amplitude was smaller in the schizophrenics than in the controls after longer interstimulus intervals. P2 amplitude was smaller in the schizophrenics only at higher stimulus intensities. P2 latency was shorter in schizophrenics except in the paradigm that varied interstimulus intervals. P3 amplitude, however, was much smaller in schizophrenics than controls ragardless of whether P3 was elicited by targets in a task or was elicited by 100 dB SPL stimuli. The loud stimuli also elicited blink reflexes that coincided with N1, but these reflexes did not vary by clinical group. Neither the amplitude of the slow wave following targets nor the sustained potential that accompanies prolonged auditory stimuli differed between schizophrenics and controls.
View details for Web of Science ID A1980JE94500002
View details for PubMedID 6153330
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P3 REDUCTION IN AUDITORY EVOKED-POTENTIALS OF SCHIZOPHRENICS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1980; 49 (5-6): 497-505
Abstract
Fifteen schizophrenics and 15 age-matched controls performed a reaction time (RT) task. A Bernoulli sequence of 85 dB SPL, 50 msec, 800 c/sec (P = 0.85) and 1200 c/sec (P = 0.15) tones was presented with an interstimulus interval of 1 sec. Subjects were instructed to press a button quickly upon hearing the 1200 c/sec tone. If a subject failed to respond within 650 msec, a 50 msec white noise burst occurred. In averages synchronized with target tones and computed without respect to RT, P3 was maximal at PZ with a mean latency of 330 msec for both schizophrenics and controls. P3 amplitude at PZ, however, averaged 6 muV in schizophrenics and 14 muV in controls (P < 0.001). Both mean RT and mean within-subject variance were greater in schizophrenices than controls. Other kinds of averages were computed to investigate the possibility that the amplitude differences were associated with different RTs or with differences in P3 latency variability in underlying trails. Averages of trials associated with short RTs (100--286 msec) had larger P3s than averages associated with long RTs (287--600 msec) (P < 0.01). Within each RT range, however, schizophrenic P3s were smaller than control P3s. Neither response-synchronized averaging nor adaptive filtering eliminated P3 amplitude differences between groups, indicating that P3 latency variability cannot account for these differences. We hypothesize that the smaller P3s in schizophrenics represent a deficit in reactivity to unexpected stimuli that is compatible with normal RT performance.
View details for Web of Science ID A1980KH37100007
View details for PubMedID 6158431
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P300 and reaction time in schizophrenics and controls.
Progress in brain research
1980; 54: 522-525
View details for PubMedID 7220962
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AGE-DIFFERENCES IN P3-REACTION TIME ASSOCIATIONS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1980; 49 (3-4): 257-265
Abstract
Eight healthy old and 12 healthy young women had event-related potentials (ERPs) recorded during the performance of a memory retrieval task. For each subject the single trial data recorded at Pz were analyzed using Woody's adaptive filter technique. The old subjects differed from the young in several respects: P3 amplitude at Pz was smaller, P3 latency and reaction time (RT) were greater, the relationship between P3 latency and RT was considerably altered. The adaptive filter increased the amplitude of P3 but the age-related amplitude difference persisted, suggesting that this difference is not due to increased latency variability with age. The old subjects had lower single trial P3-RT correlations and longer elapsed time from P3 peak to the response than did the young subjects. Both groups had greater RTs for outset items ('negative' responses) than for inset items ('positive' responses). For the young subjects P3 latency was also greater for the outset compared to the inset items but the difference was not found for the old subjects. Thus, the relationship between P3 latency and RT is altered in the aged--P3 and RT are less tightly coupled than in the young.
View details for Web of Science ID A1980KD59600005
View details for PubMedID 6158402
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CHOLINOMIMETICS AND MEMORY - EFFECT OF CHOLINE CHLORIDE
ARCHIVES OF NEUROLOGY
1980; 37 (1): 49-52
Abstract
Young normal subjects received 16 g of choline chloride in a double-blind A-B-A design. Short- and long-term memory function was evaluated. Comparison of group means indicated that choline chloride did not significantly affect short-term memory or long-term memory. However, individual subjects may have had some aspects of long-term memory affected by choline chloride treatments. The results suggest that the effect of lower doses of choline on long-term memory should be evaluated.
View details for Web of Science ID A1980JB37100012
View details for PubMedID 7350901
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AGE-RELATED-CHANGES IN AUDITORY EVENT-RELATED POTENTIALS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1980; 49 (3-4): 266-276
Abstract
Twelve elderly and 12 young women were subjects in a reaction-time task designed to elicit middle and late event-related potentials (ERP). The aged subjects differed from the young in respect to the later occurring ERP components: P2 was larger and later; P3 was later and had a different scalp distribution; the slow wave (SW) was smaller. In contrast, no age-related differences were found for N1 amplitude or latency. It is suggested that the diminution in SW amplitude contributes to the change in scalp distribution of P3 amplitude seen with age. The relationship of reaction time and P3 latency of single trials was examined by the adaptive filter technique. There was no difference between the old and young subjects as both groups revealed signficant, positive P3 latency-reaction time correlations.
View details for Web of Science ID A1980KD59600006
View details for PubMedID 6158403
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AUDITORY BRAIN-STEM AND CORTICAL EVOKED-POTENTIALS IN SCHIZOPHRENIA
BIOLOGICAL PSYCHIATRY
1980; 15 (2): 209-223
Abstract
Auditory brain stem and cortical evoked potentials were recorded from 15 schizophrenics and 15 controls. There were significant cortical evoked potential differences between the two groups. However, brain stem evoked potentials were almost identical, suggesting that the cortical evoked potential differences are not due to peripheral factors such as inability to match sensory thresholds or defects in auditory acuity.
View details for Web of Science ID A1980JK81900003
View details for PubMedID 7417612
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BETA-ENDORPHIN AND SCHIZOPHRENIA
ARCHIVES OF GENERAL PSYCHIATRY
1980; 37 (6): 635-640
Abstract
To study the effects of beta-endorphin in chronic schizophrenia, nine male patients participated in a double-blind crossover comparison of a single intravenous 20-mg injection of beta-endorphin and saline. Bolus injection of beta-endorphin from an albumin-coated syringe produced markedly higher plasma concentrations than did slow intravenous infusion from a non-albumin-coated syringe. Beta-endorphin intravenously injected in nine patients produced a statistically significant increase in serum prolactin levels. In one patient, both 10 mg of morphine sulfate and 20 mg of beta-endorphin produced similar increases in the alpha power of the EEG. In eight patients, beta-endorphin administration was associated with a statistically significant but not clinically obvious improvement in schizophrenic symptoms.
View details for Web of Science ID A1980JW99000003
View details for PubMedID 7387335
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Clinical application of sustained auditory evoked potentials.
Progress in brain research
1980; 54: 526-530
View details for PubMedID 7220963
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Effects of stimulus intensity on P300.
Progress in brain research
1980; 54: 296-300
View details for PubMedID 7220929
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On the utility of P3 latency and RT for studying cognitive processes.
Progress in brain research
1980; 54: 661-667
View details for PubMedID 7220982
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Acute and chronic effects of ethanol on event-related potentials.
Advances in experimental medicine and biology
1980; 126: 625-639
View details for PubMedID 7405699
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AGE EFFECTS ON EVENT-RELATED POTENTIALS IN A SELECTIVE ATTENTION TASK
JOURNALS OF GERONTOLOGY
1979; 34 (3): 388-395
Abstract
We used an event-related brain potential (ERP) technique developed by Hillyard et al. (1973) to test abilities to attenuate irrelevant stimuli and to detect target stimuli. Subjects, 12 healthy old (80.3 years) and 12 healthy young adults (22.0 years), heard 1500 Hz tones in one ear and 800 Hz tones in the other ear. Infrequently, the pitch of either tone was raised. During one run, infrequent tones in the right ear were targets, and in the other run those in the left ear were targets. Subjects counted targets. For both groups, an early component of the ERP (N1) was larger to tones in the attended ear than in the unattended ear, and a later component (P3) was largest to the target. This suggests that both groups can attenuate irrelevant stimuli and can use stimulus probability information in this task. That P3 was later for old subjects suggests that they take longer to decide stimulus relevance.
View details for Web of Science ID A1979GU67100010
View details for PubMedID 429773
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INTOLERANCE AND EXTREMISM IN A CORRECTIONAL INSTITUTION - PERCEIVED ETHNIC-RELATIONS APPROACH
AMERICAN JOURNAL OF PSYCHIATRY
1979; 136 (11): 1438-1443
Abstract
The authors used an ecological approach to analyze the interaction of ethnicity, environment, personality, and ideology that led to racial intolerance, ethnic strife, and the existence of a self-styled neo-Nazi group in a correctional institution for youthful offenders. Staff members completed a questionnaire on which they rated the behavior of each of 320 inmates toward his own and other ethnic groups. The inmate's membership, if any, in a "power" subgroup was also noted. Results indicated a correlation between antagonistic patterns of ethnic relations and receptivity to racial propaganda and ideology. Further research focusing on the perceived ethnic relations climate is necessary to determine whether the patterns found in this institution are typical and to ascertain explanations for this correlation.
View details for Web of Science ID A1979HT07000010
View details for PubMedID 495797
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State-trait considerations of event-related potential markers of psychopathology.
Psychopharmacology bulletin
1979; 15 (1): 36-39
View details for PubMedID 419247
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HUMAN EEG RESPONSE TO BETA-ENDORPHIN
PSYCHIATRY RESEARCH
1979; 1 (1): 83-88
Abstract
Beta-endorphin, morphine, and saline were given intravenously to a single schizophrenic subject on separate occasions in a double-blind design. EEG spectral analyses performed on data collected before and after drug injection demonstrated that beta-endorphin and morphine produced similar increases in alpha power within 5 to 15 minutes after injection. This effect could be distinguished from two placebo (saline) injections. These data suggest that intravenous beta-endorphin can produce changes in the central nervous system in humans.
View details for Web of Science ID A1979HN77000011
View details for PubMedID 298341
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EVENT-RELATED POTENTIAL CHANGES IN HEALTHY AGED FEMALES
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1979; 46 (1): 81-86
Abstract
Neurophysiological changes in the central nervous system were demonstrated with EEG even-related potentials in healthy, aged women. Compared to young women, the aged women showed decreased amplitude of the late sustained potential (SP), increased P2 latency, disruption of the normal stimulus intensity-response amplitude function of P2 and increased amplitude of the P1 component. These age-related changes are interpreted as neurophysiological reflections of CNS deterioration found in non-senile elderly persons.
View details for Web of Science ID A1979GD90100009
View details for PubMedID 88334
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EVENT-RELATED POTENTIAL CHANGES IN CHRONIC-ALCOHOLICS
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
1979; 47 (6): 637-647
Abstract
Ten chronic alcoholics (10+ year alcoholic drinking history) and ten age and sex matched controls were tested on an ERP paradigm which elicited a large P3 component. The N1 and P2 sensory evoked potential components did not differ in amplitude or latency between the two groups. The latency of the P3 was significantly longer for the alcoholics than the controls for both a response and non-response stimulus. This finding is consistent with the results seen in a variety of dementias and is offered as evidence of the dementing effects of prolonged alcoholism in this group of subjects. While the P3 latencies were prolonged for the alcoholics, their reaction times were not different from the controls. Single trial analysis using Woody's adaptive filter also demonstrated that the single trial estimates for the 3 latency were significantly prolonged for the alcoholics. The single trial correlation between the P3 latency and each trial's corresponding reaction time was significantly greater for the alcoholics than for the controls.
View details for Web of Science ID A1979HY33700001
View details for PubMedID 91494
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EFFECTS OF ETHANOL AND MEPERIDINE ON AUDITORY EVOKED-POTENTIALS
DRUG AND ALCOHOL DEPENDENCE
1979; 4 (5): 371-380
Abstract
The effects of ethanol and meperidine on the auditory evoked potential (AEP) to stimuli of different intensities were investigated. Sixteen normal male volunteers received ethanol, 0.8 ml/kg, 100 mg meperidine, and a placebo on different days in a double-blind study. AEPs were recorded from Fz, Cz and Pz electrode placements. The stimuli were 500 msec 1000 Hz tones at 50, 60, 70 and 80 dB sound pressure level presented in a pseudo-random sequence. Meperidine had no significant effect on AEP variables. Ethanol reduced AEP activity between 24 and 250 msec but had no effect on the sustained potential measured between 300 and 450 msec.
View details for Web of Science ID A1979GY68200001
View details for PubMedID 510179
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EEG EFFECTS OF PHYSOSTIGMINE AND CHOLINE CHLORIDE IN HUMANS
PSYCHOPHARMACOLOGY
1979; 62 (3): 225-233
Abstract
Seventeen normal volunteers received either 0.5 mg, 1.5 mg, or 2.5 mg physostigmine i.v. in a placebo-drug-placebo single-blind design. EEG was recorded simultaneously and analyzed by computerized spectral analysis. Eleven healthy elderly volunteers (mean age = 69.1 years) with mild memory impairment were treated with placebo, followed by oral choline chloride (either 8 g/day for 3 weeks, or 16 g/day for 1 week), and then, again, placebo. Recordings of spontaneous EEG and EEG event-related potentials (contingent negative variation) were obtained during both placebo and choline treatments. The larger doses of physostigmine produced an increase in low frequency activity and a slowing of the peak alpha frequency. Oral choline chloride had no effect on the EEG as measured by spectral analysis, but appears to have differential effects on contingent negative variation (CNV) amplitude and reaction time, depending upon the initial CNV amplitude.
View details for Web of Science ID A1979GW41600004
View details for PubMedID 111288
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GROUP-PSYCHOTHERAPY AS AN ADJUNCT TO LITHIUM MAINTENANCE
AMERICAN JOURNAL OF PSYCHIATRY
1979; 136 (4): 455-456
View details for Web of Science ID A1979GQ52400022
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VIGILANCE AND HUMAN ATTENTION UNDER CONDITIONS OF METHYLPHENIDATE AND SECOBARBITAL INTOXICATION - ASSESSMENT USING BRAIN POTENTIALS
PSYCHOPHYSIOLOGY
1978; 15 (2): 116-125
View details for Web of Science ID A1978ES94700003
View details for PubMedID 652905
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MARIHUANA EFFECTS ON ASSOCIATIONS TO NOVEL STIMULI
JOURNAL OF NERVOUS AND MENTAL DISEASE
1978; 166 (5): 362-364
Abstract
Sixteen college-educated male subjects were given an object description task during placebo conditions and while intoxicated with marijuana extract cookies calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol, a dose within the range of usual social use. The task was scored for fluency, flexibility, elaboration, and uniqueness, all of which represent associational thinking and are considered to be components of creativity. Marijuana did not enhance any of these measures.
View details for Web of Science ID A1978FA84600008
View details for PubMedID 650201
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DISTRIBUTION OF ATTENTION ACROSS AUDITORY INPUT CHANNELS - ASSESSMENT USING HUMAN EVOKED-POTENTIAL
PSYCHOPHYSIOLOGY
1978; 15 (5): 466-473
View details for Web of Science ID A1978FR95200013
View details for PubMedID 693759
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PHYSOSTIGMINE - IMPROVEMENT OF LONG-TERM-MEMORY PROCESSES IN NORMAL HUMANS
SCIENCE
1978; 201 (4352): 272-274
Abstract
Nineteen normal male subjects received 1.0 milligram of physostigmine or 1.0 milligram of saline by a slow intravenous infusion on two nonconsecutive days. Physostigmine significantly enhanced storage of information into long-term memory. Retrieval of information from long-term memory was also improved. Short-term memory processes were not significantly altered by physostigmine.
View details for Web of Science ID A1978FF63800020
View details for PubMedID 351807
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MARIHUANA AND MEMORY INTRUSIONS
JOURNAL OF NERVOUS AND MENTAL DISEASE
1977; 165 (6): 381-386
Abstract
Sixteen college-educated male subjects were tested on free-recall lists during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. On each testing day subjects studied six lists using a regular overt rehearsal procedure and six lists using an association-overt rehearsal procedure in which they were to rehearse alound both list items and associations to those items. Both marijuana and the association-rehearsal procedure reduced the number of correct recalls and increased the number of intrusions (nonlist items which were incorrectly recalled as having been on the list to be learned). The intrusions were divided into three categories: a) words found on prior lists; b) associates spoken during the rehearsal; or c) totally new works not previously mentioned. Marijuana significantly increased the number of new intrusions; the association-rehearsal procedure did not. This result suggests that one of the effects of marijuana on cognitive functions in humans is to increase the number of intrusive thoughts and this may be the mechanism involved in some of the thought disorder observed with marijuana intoxication.
View details for Web of Science ID A1977EF05800003
View details for PubMedID 591936
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NARCOLEPSY, PARANOID PSYCHOSIS, AND TARDIVE-DYSKINESIA - PHARMACOLOGICAL DILEMMA
JOURNAL OF NERVOUS AND MENTAL DISEASE
1977; 164 (4): 293-297
Abstract
The case history of a 54-year-old man with concomitant narcolepsy, paranoid psychosis, and tardive dyskinesia is presented. These disorders may all result from alteration in catecholamines, serotonin, and/or acetylcholine in the central nervous system. The interactions of the various psychopharmacological agents usually used to treat the disorders when they occur separately are considered in terms of current neurotransmitter hypotheses. The management of this case creates a pharmacological dilemma; the agents used for treatment of each of the disorders separately exacerbate one or both of the other two syndromes.
View details for Web of Science ID A1977DC69300011
View details for PubMedID 845600
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EFFECT OF SLEEP STAGE AND STIMULUS-INTENSITY ON AUDITORY AVERAGE EVOKED-RESPONSES
PSYCHOPHYSIOLOGY
1975; 12 (6): 707-712
View details for Web of Science ID A1975AU99500018
View details for PubMedID 171700
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INDIVIDUAL DIFFERENCES IN EYE-MOVEMENT PATTERNS
PERCEPTUAL AND MOTOR SKILLS
1972; 35 (3): 895-901
View details for Web of Science ID A1972O311300042
View details for PubMedID 4643983
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Enhancement of the average evoked response to tone onset and cessation.
Psychophysiology
1971; 8 (3): 332-339
View details for PubMedID 5093976
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USE OF A SMALL PROCESS CONTROL COMPUTER IN A PSYCHOPHYSIOLOGICAL LABORATORY
PSYCHOPHYSIOLOGY
1971; 8 (4): 538-?
View details for Web of Science ID A1971K375400013
View details for PubMedID 5094937
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HANDEDNESS AND CORTICAL HEMISPHERE EFFECTS IN SINE WAVE STIMULATED EVOKED RESPONSES
NEUROPSYCHOLOGIA
1971; 9 (2): 237-?
View details for Web of Science ID A1971J548100011
View details for PubMedID 5149062
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HYPOPARATHYROIDISM IN A PATIENT WITH LONGSTANDING IRON STORAGE DISEASE
ANNALS OF INTERNAL MEDICINE
1970; 73 (2): 259-?
View details for Web of Science ID A1970H009700012
View details for PubMedID 5454262