My current research is focused on advancing our understanding on ‘how the human brain works’ by studying the relationship between brain structure and function using multimodal imaging approaches (e.g., MRI, DTI, rsMRI, fMRI) in healthy and degraded brain systems.
HEALTHY AGING AND AGING WITH DISEASE: One research focus is on the cognitive and motor neurofunctional changes in healthy aging, neurodegeneration in people living with HIV infection (PLWH) and Parkinson’s disease (PD). Despite the many challenges, some HIV patients manage to age successfully, most likely by redistribution of neural network resources to enhance function, as occurs in healthy elderly; such compensation could be curtailed by emerging Parkinsonism. This collaborative research between SRI International, Stanford Psychiatry, and Stanford Neurology aims at gaining a better understanding of the neurodegenerative and neuroadaptive processes that occur with healthy aging, PLWH and PD, risk for cognitive decline and functional impairment.
ALCOHOL ADDICTION: Another research focus is on the effects of chronic alcoholism on brain structure and function. Executive control functions are disturbed in addiction, and interact with attention, emotion, and reward functions. This research focuses on the neurofunctional mechanisms of automatic attentional bias (toward salient events, emotional and alcohol cues) and negative priming, and their role for relapse and the treatment of AUD. Recovered drinkers can remain compromised in their ability to perform routine daily tasks, such as driving or operating machines that rely on integrating information from multiple sensory channels for efficient performance. My research uses multimodal neuroimaging derived connectivity measures to identify structural and functional neurocircuits compromised in AUD, and those that may serve functional recovery with abstinence.
ADOLESCENT BRAIN DEVELOPMENT: A recent research focus is on adolescent brain functional development. The transition from adolescence to adult cognitive maturity and emotional control is marked by dynamic neurodevelopmental plasticity. In collaboration with the sleep lab at SRI International, my research aims to identify specific patterns of altered neural responses in adolescent girls and boys with depressed mood and whether socio-emotional peer interactions and sleep disturbances moderate the association between neural responses and depressive symptom severity. I am part of two consortium projects about adolescent development: The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) and the Adolescent Brain Cognitive Development study (ABCD).
Episodic memory deficit in HIV infection: common phenotype with Parkinson's disease, different neural substrates.
Brain structure & function
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
The distortions of the free water model for diffusion MRI data when assuming single compartment relaxometry and proton density.
Physics in medicine and biology
To document the bias of the simplified free water model of diffusion MRI (dMRI) signal vis-a-vis a specific model which, in addition to diffusion, incorporates compartment-specific proton density (PD), T1 recovery during repetition time (TR), and T2 decay during echo time (TE).Both models assume that volume fraction f of the total signal in any voxel arises from the free water compartment (fw) such as cerebrospinal fluid (CSF) or edema, and the remainder (1-f) from hindered water (hw) which is constrained by cellular structures such as white matter (WM). The specific and simplified models are compared on a synthetic dataset, using a range of PD, T1 and T2 values. We then fit the models to an in vivo healthy brain dMRI dataset. For both synthetic and in vivo data we use experimentally feasible TR, TE, signal-to-noise ratio (SNR) and physiologically plausible diffusion profiles.From the simulations we see that the difference between the estimated simplified f and specific f is largest for mid-range ground-truth f, and it increases as SNR increases. The estimation of volume fraction f is sensitive to the choice of model, simplified or specific, but the estimated diffusion parameters are robust. Specific f is more accurate and precise than simplified f. In the white matter (WM) regions of the in vivo images, specific f is lower than simplified f.In dMRI models for free water, accounting for compartment specific PD, T1 and T2, in addition to diffusion, improves the estimation of model parameters. This extra model specification attenuates the estimation bias of compartmental volume fraction without affecting the estimation of other diffusion parameters.
View details for DOI 10.1088/1361-6560/acb30b
View details for PubMedID 36638532
Detecting negative valence symptoms in adolescents based on longitudinal self-reports and behavioral assessments.
Journal of affective disorders
BACKGROUND: Given the high prevalence of depressive symptoms reported by adolescents and associated risk of experiencing psychiatric disorders as adults, differentiating the trajectories of the symptoms related to negative valence at an individual level could be crucial in gaining a better understanding of their effects later in life.METHODS: A longitudinal deep learning framework is presented, identifying self-reported and behavioral measurements that detect the depressive symptoms associated with the Negative Valence System domain of the NIMH Research Domain Criteria (RDoC).RESULTS: Applied to the annual records of 621 participants (age range: 12 to 17 years) of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), the deep learning framework identifies predictors of negative valence symptoms, which include lower extraversion, poorer sleep quality, impaired executive control function and factors related to substance use.LIMITATIONS: The results rely mainly on self-reported measures and do not provide information about the underlying neural correlates. Also, a larger sample is required to understand the role of sex and other demographics related to the risk of experiencing symptoms of negative valence.CONCLUSIONS: These results provide new information about predictors of negative valence symptoms in individuals during adolescence that could be critical in understanding the development of depression and identifying targets for intervention. Importantly, findings can inform preventive and treatment approaches for depression in adolescents, focusing on a unique predictor set of modifiable modulators to include factors such as sleep hygiene training, cognitive-emotional therapy enhancing coping and controllability experience and/or substance use interventions.
View details for DOI 10.1016/j.jad.2022.06.002
View details for PubMedID 35688394
Disruption of cerebellar-cortical functional connectivity predicts balance instability in alcohol use disorder.
Drug and alcohol dependence
2022; 235: 109435
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
The Pandemic's Toll on Young Adolescents: Prevention and Intervention Targets to Preserve Their Mental Health.
The Journal of adolescent health : official publication of the Society for Adolescent Medicine
PURPOSE: Adolescence is characterized by dramatic physical, social, and emotional changes, making teens particularly vulnerable to the mental health effects of the COVID-19 pandemic. This longitudinal study identifies young adolescents who are most vulnerable to the psychological toll of the pandemic and provides insights to inform strategies to help adolescents cope better in times of crisis.METHODS: A data-driven approach was applied to a longitudinal, demographically diverse cohort of more than 3,000 young adolescents (10-14years) participating in the ongoing Adolescent Brain Cognitive Development Study in the United States, including multiple prepandemic visits and three assessments during the COVID-19 pandemic (May-August 2020). We fitted machine learning models and provided a comprehensive list of predictors of psychological distress in individuals.RESULTS: Positive affect, stress, anxiety, and depressive symptoms were accurately detected with our classifiers. Female sex and prepandemic internalizing symptoms and sleep problems were strong predictors of psychological distress. Parent- and youth-reported pandemic-related psychosocial factors, including poorer quality and functioning of family relationships, more screen time, and witnessing discrimination in relation to the pandemic further predicted youth distress. However, better social support, regular physical activities, coping strategies, and healthy behaviors predicted better emotional well-being.CONCLUSIONS: Findings highlight the importance of social connectedness and healthy behaviors, such as sleep and physical activity, as buffering factors against the deleterious effects of the pandemic on adolescents' mental health. They also point to the need for greater attention toward coping strategies that help the most vulnerable adolescents, particularly girls and those with prepandemic psychological problems.
View details for DOI 10.1016/j.jadohealth.2021.11.023
View details for PubMedID 35090817
A Longitudinal Examination of Alcohol-Related Blackouts as a Predictor of Changes in Learning, Memory, and Executive Function in Adolescents.
Frontiers in psychiatry
2022; 13: 866051
Introduction: In adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study.Methods: Descriptive analyses of the NCANDA sample (N = 831, 50.9% female, 12-21 years at baseline) identified ARB patterns within participants with an ARB history (n = 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (n = 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMTi), and delayed (PFMTd) recognition trials, and the Rey Complex Figure Test copy (RCFTc), immediate recall (RCFTi), and delayed recall (RCFTd) trials. Multivariate models were fit for raw accuracy scores from each measure, with ARB history (i.e., presence of past-year ARBs) as the main independent variable. Age, sex, race, socioeconomic status, assessment site, and alcohol use (i.e., past-year frequency) were included as covariates. Interaction effects between ARB history and alcohol use frequency were tested.Results: By year five, 16% of participants had experienced at least one ARB (59% of whom reported > 1 ARB and 57% of whom had an ARB lasting > 1 h). After controlling for demographics and alcohol use, ARB history predicted attenuated PFMTd performance growth at year one. Interaction effects between ARB history and alcohol use frequency predicted attenuated PFMTd performance growth at years one and two. ARB history predicted attenuated RCFTi and RCFTd performance growth by year four, but not PCET or PLBT performance over time. By contrast, greater past-year alcohol use predicted attenuated PFMTi and PFMTd performance growth between years two and four in adolescents without an ARB history.Conclusion: We found that ARBs predict distinct, lasting changes in learning and memory for visual information, with results suggesting that the developing brain is vulnerable to ARBs during adolescence and emerging adulthood.
View details for DOI 10.3389/fpsyt.2022.866051
View details for PubMedID 35599753
Neurofunctional characteristics of executive control in older people with HIV infection: a comparison with Parkinson's disease.
Brain imaging and behavior
Expression of executive dysfunctions is marked by substantial heterogeneity in people living with HIV infection (PLWH) and attributed to neuropathological degradation of frontostriatal circuitry with age and disease. We compared the neurophysiology of executive function in older PLWH and Parkinson's disease (PD), both affecting frontostriatal systems. Thirty-one older PLWH, 35 individuals with PD, and 28 older healthy controls underwent executive task-activated fMRI, neuropsychological testing, and a clinical motor exam. fMRI task conditions distinguished cognitive control operations, invoking a lateral frontoparietal network, and motor control operations, activating a cerebellar-precentral-medial prefrontal network. HIV-specific findings denoted a prominent sensorimotor hypoactivation during cognitive control and striatal hypoactivation during motor control related to CD4+ T cell count and HIV disease duration. Activation deficits overlapped for PLWH and PD, relative to controls, in dorsolateral frontal, medial frontal, and middle cingulate cortices for cognitive control, and in limbic, frontal, parietal, and cerebellar regions for motor control. Thus, despite well-controlled HIV infection, frontostriatal and sensorimotor activation deficits occurred during executive control in older PLWH. Overlapping activation deficits in posterior cingulate and hippocampal regions point toward similarities in mesocorticolimbic system aberrations among older PLWH and PD. The extent of pathophysiology in PLWH was associated with variations in immune system health, neural signature consistent with subclinical parkinsonism, and mild neurocognitive impairment. The failure to adequately engage these pathways could be an early sign for cognitive and motor functional decline in the aging population of PLWH.
View details for DOI 10.1007/s11682-022-00645-6
View details for PubMedID 35294979
Growth Trajectories of Cognitive and Motor Control in Adolescence: How Much Is Development and How Much Is Practice?
View details for DOI 10.1037/neu0000771
View details for Web of Science ID 000735242200001
The effects of mood and cognition on daily functioning and quality of life in older people living with HIV and people with Parkinson's disease.
OBJECTIVE: In light of the increased longevity of people living with HIV infection (PLWH) undergoing antiretroviral therapy (ART), the present study aimed to determine the effects of mood disturbances alongside cognitive and motor symptoms on activities of daily living (ADLs) and quality of life (QOL) in older PLWH in comparison to an aging control sample without notable medical history (CTL) and individuals with Parkinson's disease (PD).METHOD: Forty-one PLWH, 41 individuals with PD, and 37 CTL, aged 45-79 years, underwent neuropsychological, psychological, and neurological assessment including depressive and anxiety symptoms, physical (ADL-p) and instrumental (ADL-i) daily activities, Unified Parkinson's Disease Rating Scale motor ADLs (ADL-UPDRS-II), QOL, and cognitive and motor functions. Hierarchical regression analyses assessed the relative contribution of predictors including demographics, disease-related factors, comorbid conditions, and mood-related factors for ADL and QOL scales.RESULTS: PLWH and PD participants reported more depressive symptoms and higher anxiety and worse QOL and ADL-i than CTL. The PD group had greater ADL-p and motor-related ADL-UPDRS-II difficulties than PLWH and CTL groups. In PLWH, medical comorbidities and alcohol use disorder (AUD)/substance use disorder (SUD) histories significantly contributed to poor physical and motor ADLs. Mood scores, particularly depressive symptoms, were independent predictors of poor QOL and most ADLs in both clinical groups, above the contribution of cognitive compromise.CONCLUSIONS: Mood symptoms contribute significantly to poor ADLs and QOL in people aging with chronic diseases such as long-term HIV infection and PD. Comprehensive assessment and treatment of mood symptoms are recommended for ensuring optimal functional independence and life quality. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View details for DOI 10.1037/neu0000760
View details for PubMedID 34323563
Alcohol Use Disorder and Its Comorbidity With HIV Infection Disrupts Anterior Cingulate Cortex Functional Connectivity.
Biological psychiatry. Cognitive neuroscience and neuroimaging
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
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
Alterations of Brain Signal Oscillations in Older Individuals with HIV Infection and Parkinson's Disease.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
More than 30years after the human immunodeficiency virus (HIV) epidemic, HIV patients are now aging due to the advances of antiretroviral therapy. With immunosenescence and the susceptibility of dopamine-rich basal ganglia regions to HIV-related injury, older HIV patients may show neurofunctional deficits similar to patients with Parkinson's disease (PD). We examined the amplitudes of low frequency fluctuations (ALFF) across different frequency bands of the BOLD signal in 30 older HIV-infected individuals, 33 older healthy controls, and 36 PD patients. Participants underwent resting-state fMRI, neuropsychological testing, and a clinical motor exam. HIV patients mainly showed abnormalities in cortical ALFF with reduced prefrontal amplitudes and enhanced sensorimotor and inferior temporal amplitudes. Frontal hypoactivation was overlapping for HIV and PD groups and different from controls. PD patients further exhibited reduced pallidum amplitudes compared to the other groups. In the HIV group, lower pallidum amplitudes were associated with lower CD4+ nadir and CD4+ T cell counts. Abnormalities in ALFF dynamics were largely associated with cognitive and motor functioning in HIV and PD groups. The disruption of neurofunctional frequency dynamics in subcortical-cortical circuits could contribute to the development of cognitive and motor dysfunction and serve as a biomarker for monitoring disease progression with immunosenescence. Graphical Abstract.
View details for DOI 10.1007/s11481-020-09914-x
View details for PubMedID 32291601
Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson's disease.
Journal of neuropsychology
Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson's disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45-79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4+ T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.
View details for DOI 10.1111/jnp.12227
View details for PubMedID 33029951
Adolescent alcohol use disrupts functional neurodevelopment in sensation seeking girls.
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
Quantitative Digitography Measures Fine Motor Disturbances in Chronically Treated HIV Similar to Parkinson’s Disease
Frontier in Aging Neuroscience
Introduction: Motor and cognitive deficits were compared in aging, chronically treated human immunodeficiency virus (HIV) people, people with mild-to-moderate stage Parkinson's disease (PD), and healthy controls. Methods: Groups consisted of 36 people with PD, 28 with HIV infection, and 28 healthy controls. Motor function was assessed with the Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) and a rapid alternating finger tapping (RAFT) task on an engineered keyboard known as Quantitative Digitography (QDG). Executive function, verbal memory, and visuospatial processing were assessed using standard neuropsychological tests. Results: HIV demonstrated RAFT deficits similar to PD such as reduced amplitude (P = 0.023) and greater amplitude variability (P = 0.019) in the index finger when compared to controls. This fine motor disturbance correlated with HIV's immune health, measured by their CD4+ T cell count (P < 0.01). The UPDRS did not yield motor differences between HIV and controls. Executive function and verbal memory were impaired in HIV (P = 0.006, P = 0.016, respectively), but not in PD; visuospatial processing was similarly impaired in HIV and PD (P < 0.05) although motor deficits predominated in PD. Conclusions: Fine motor bradykinesia measured quantitatively by QDG RAFT holds promise as a marker of motor decline related to current immune health in aging HIV patients and may be useful in longitudinal studies regarding mechanisms of immunosenescence vs. potential toxicity of combination antiretroviral therapy (cART) in this population. Additionally, motor and cognitive networks in HIV may be affected differently as the disease progresses as observed in the differential patterns of impairment between HIV and PD, providing insight into the mechanisms of brain deterioration in HIV.
View details for DOI 10.3389/fnagi.2020.539598
View details for PubMedCentralID PMC7575770
Phases of procedural learning and memory: characterisation with perceptual-motor sequence tasks
JOURNAL OF COGNITIVE PSYCHOLOGY
View details for DOI 10.1080/20445911.2019.1642897
View details for Web of Science ID 000476440800001
Establishing a framework for neuropathological correlates and glymphatic system functioning in Parkinson's disease.
Neuroscience and biobehavioral reviews
Recent evidence has advanced our understanding of the function of sleep to include removal of neurotoxic protein aggregates via the glymphatic system. However, most research on the glymphatic system utilizes animal models, and the function of waste clearance processes in humans remains unclear. Understanding glymphatic function offers new insight into the development of neurodegenerative diseases that result from toxic protein inclusions, particularly those characterized by neuropathological sleep dysfunction, like Parkinson's disease (PD). In PD, we propose that glymphatic flow may be compromised due to the combined neurotoxic effects of alpha-synuclein protein aggregates and deteriorated dopaminergic neurons that are linked to altered REM sleep, circadian rhythms, and clock gene dysfunction. This review highlights the importance of understanding the functional role of glymphatic system disturbance in neurodegenerative disorders and the subsequent clinical and neuropathological effects on disease progression. Future research initiatives utilizing noninvasive brain imaging methods in human subjects with PD are warranted, as in vivo identification of functional biomarkers in glymphatic system functioning may improve clinical diagnosis and treatment of PD.
View details for DOI 10.1016/j.neubiorev.2019.05.016
View details for PubMedID 31132378
Effects of age, sex, and puberty on neural efficiency of cognitive and motor control in adolescents.
Brain imaging and behavior
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
Longitudinally consistent estimates of intrinsic functional networks
Human Brain Mapping
View details for DOI 10.1002/hbm.24541
Brain activation to cannabis- and alcohol-related words in alcohol use disorder.
Psychiatry research. Neuroimaging
2019; 294: 111005
Cannabis abuse commonly co-occurs with alcohol use disorder (AUD). With increased acceptance and accessibility to cannabis in the US, it is imperative to understand the psychological and neural mechanisms of concurrent alcohol and cannabis use. We hypothesized that neural alcohol-cue conditioning may extent to other drug-related stimuli, such as cannabis, and underwrite the loss of control over reward-driven behavior. Task-activated fMRI examined the neural correlates of alcohol- and cannabis-related word cues in 21 abstinent AUD and 18 control subjects. Relative to controls, AUD showed behavioral attentional biases and frontal hypoactivation to both alcohol- and cannabis-related words. This cue-elicited prefrontal hypoactivation was related to higher lifetime alcohol consumption (pcorrected < 0.02) and modulated by past cannabis use histories (p ≦ 0.001). In particular, frontal hypoactivation to both alcohol and cannabis cues was pronounced in AUD without prior cannabis exposure. Overall, frontal control mechanisms in abstinent AUD were not sufficiently engaged to override automatic alcohol and cannabis-related intrusions, enhancing the risk for relapse and potentially for alcohol and cannabis co-use with the increased social acceptance and accessibility in the US.
View details for DOI 10.1016/j.pscychresns.2019.111005
View details for PubMedID 31715379
Occipito-Temporal Sensitivity and Emotional Faces in Alcohol Use Disorder
NEUROSCIENCE OF ALCOHOL: MECHANISMS AND TREATMENT
View details for DOI 10.1016/B978-0-12-813125-1.00028-3
View details for Web of Science ID 000535128700029
Information processing deficit in older adults with HIV infection: A comparison with Parkinson's disease.
OBJECTIVE: Individuals with HIV treated with antiretroviral therapy can expect to reach average life span, making them susceptible to combined disease and aging effects on cognitive and motor functions. Slowed processing speed in HIV is a concern for cognitive and everyday functioning and is sensitive to declines in aging. We hypothesized that information processing (IP) deficits, over and above that expected with normal aging, would occur in older HIV patients similar to those observed in Parkinson's disease (PD) patients, with both conditions affecting frontostriatal pathways.METHOD: Groups comprised 26 individuals with HIV infection, 29 with mild-to-moderate PD, and 21 healthy controls (C). Speed of IP was assessed with the oral version of the Symbol Digit Modalities Test and the color naming condition of the Golden Stroop Task.RESULTS: The HIV group was impaired on speed of IP tasks compared with both the C and PD groups. Even after controlling for normal aging effects, older age in the HIV group correlated with IP slowing. Slower IP speed was associated with poorer general cognitive ability and more extrapyramidal motor signs in older HIV-infected individuals.CONCLUSIONS: The notable effects of impaired IP speed, over and above neurotypical age-related declines, indicate that older HIV-infected individuals may have an enhanced vulnerability for developing nonmotor and motor symptoms despite antiretroviral therapy. Assessing for oral IP speed may provide the unique opportunity to identify early signs of progressive clinical declines in HIV. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
View details for PubMedID 30475047
Aberrant blood-oxygen-level-dependent signal oscillations across frequency bands characterize the alcoholic brain
2018; 23 (2): 824–35
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
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
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
Deviant functional activation and connectivity of the right insula are associated with lack of awareness of episodic memory impairment in nonamnesic alcoholism
2017; 95: 15–28
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
Influences of Age, Sex, and Moderate Alcohol Drinking on the Intrinsic Functional Architecture of Adolescent Brains.
View details for DOI 10.1093/cercor/bhx014
View details for PubMedID 28168274
The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.
Brain imaging and behavior
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
Differential compromise of prospective and retrospective metamemory monitoring and their dissociable structural brain correlates
2016; 81: 192-202
View details for DOI 10.1016/j.cortex.2016.05.002
View details for Web of Science ID 000381163900017
Brain responses to emotional salience and reward in alcohol use disorder.
Brain imaging and behavior
2016; 10 (1): 136-146
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
Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention - A Comparison with Parkinson's Disease
2015; 25 (4): 424-438
View details for DOI 10.1007/s11065-015-9305-x
View details for Web of Science ID 000365807600006
The Resting Brain of Alcoholics
2015; 25 (11): 4155-4168
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
Task-rest modulation of basal ganglia connectivity in mild to moderate Parkinson's disease.
Brain imaging and behavior
2015; 9 (3): 619-638
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
Compromised frontocerebellar circuitry contributes to nonplanning impulsivity in recovering alcoholics.
2014; 231 (23): 4443-4453
Degradation of frontocerebellar circuitry is a principal neural mechanism of alcoholism-related executive dysfunctions affecting impulse control and cognitive planning.We tested the hypothesis that alcoholic patients would demonstrate compromised dorsal anterior cingulate cortex (dACC) -cerebellar functional connectivity when adjusting their strategies to accommodate uncertain conditions and would recruit compensatory brain regions to overcome ineffective response patterns.Twenty-six alcoholics and 26 healthy participants underwent functional MRI in two sequential runs while performing a decision-making task. The first run required a response regardless of level of ambiguity of the stimuli; the second run allowed a PASS option (i.e., no response choice), which was useful on ambiguous trials.Healthy controls demonstrated strong synchronous activity between the dACC and cerebellum while planning and executing a behavioral strategy. By contrast, alcoholics showed synchronous activity between the dACC and the premotor cortex, perhaps enabling successful compensation for accuracy and reaction time in certain conditions; however, a negative outcome of this strategy was rigidity in modifying response strategy to accommodate uncertain conditions. Compared with the alcoholic group, the control group had lower nonplanning impulsiveness, which correlated with using the option PASS to respond in uncertain conditions.These findings suggest that compromised dACC-cerebellar functional circuitry contributes to recruitment of an alternative network-dACC-premotor cortex- to perform well under low-risk, unambiguous conditions. This compensatory network, however, was inadequate to enable the alcoholics to avert making poor choices in planning and executing an effective behavioral strategy in high-risk, uncertain conditions.
View details for DOI 10.1007/s00213-014-3594-2
View details for PubMedID 24781521
Cognition, emotion, and attention.
Handbook of clinical neurology
2014; 125: 341-354
Deficits of attention, emotion, and cognition occur in individuals with alcohol abuse and addiction. This review elucidates the concepts of attention, emotion, and cognition and references research on the underlying neural networks and their compromise in alcohol use disorder. Neuroimaging research on adolescents with family history of alcoholism contributes to the understanding of pre-existing brain structural conditions and characterization of cognition and attention processes in high-risk individuals. Attention and cognition interact with other brain functions, including perceptual selection, salience, emotion, reward, and memory, through interconnected neural networks. Recent research reports compromised microstructural and functional network connectivity in alcoholism, which can have an effect on the dynamic tuning between brain systems, e.g., the frontally based executive control system, the limbic emotion system, and the midbrain-striatal reward system, thereby impeding cognitive flexibility and behavioral adaptation to changing environments. Finally, we introduce concepts of functional compensation, the capacity to generate attentional resources for performance enhancement, and brain structure recovery with abstinence. An understanding of the neural mechanisms of attention, emotion, and cognition will likely provide the basis for better treatment strategies for developing skills that enhance alcoholism therapy adherence and quality of life, and reduce the propensity for relapse.
View details for DOI 10.1016/B978-0-444-62619-6.00020-3
View details for PubMedID 25307584
A Selective Insular Perfusion Deficit Contributes to Compromised Salience Network Connectivity in Recovering Alcoholic Men
2013; 74 (7): 547-555
View details for DOI 10.1016/j.biopsych.2013.02.026
View details for Web of Science ID 000324310000012
Midbrain-Driven Emotion and Reward Processing in Alcoholism
2013; 38 (10): 1844-1853
View details for DOI 10.1038/npp.2013.102
View details for Web of Science ID 000323165500002
Fiber tract-driven topographical mapping (FTTM) reveals microstructural relevance for interhemispheric visuomotor function in the aging brain.
2013; 77: 195-206
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
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
IMPLICIT ALCOHOL-RELATED ASSOCIATIONS AFFECT DECISION-MAKING IN ABSTINENT ALCOHOLICS
36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
WILEY-BLACKWELL. 2013: 28A–28A
View details for Web of Science ID 000318998300070
Modulation of limbic-cerebellar functional connectivity enables alcoholics to recognize who is who.
Brain structure & function
2013; 218 (3): 683-695
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
Remapping the brain to compensate for impairment in recovering alcoholics.
2013; 23 (1): 97-104
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
Visual Search and the Aging Brain: Discerning the Effects of Age-Related Brain Volume Shrinkage on Alertness, Feature Binding, and Attentional Control
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
Remapping the Brain to Compensate for Impairment in Recovering Alcoholics
2013; 23 (1): 97-104
View details for DOI 10.1093/cercor/bhr381
View details for Web of Science ID 000312106300010
Visual search and the aging brain: discerning the effects of age-related brain volume shrinkage on alertness, feature binding, and attentional control.
2013; 27 (1): 48-59
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
How Acute and Chronic Alcohol Consumption Affects Brain Networks: Insights from Multimodal Neuroimaging
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
2012; 36 (12): 2017-2027
Multimodal imaging combining 2 or more techniques is becoming increasingly important because no single imaging approach has the capacity to elucidate all clinically relevant characteristics of a network.This review highlights recent advances in multimodal neuroimaging (i.e., combined use and interpretation of data collected through magnetic resonance imaging [MRI], functional MRI, diffusion tensor imaging, positron emission tomography, magnetoencephalography, MR perfusion, and MR spectroscopy methods) that leads to a more comprehensive understanding of how acute and chronic alcohol consumption affect neural networks underlying cognition, emotion, reward processing, and drinking behavior.Several innovative investigators have started utilizing multiple imaging approaches within the same individual to better understand how alcohol influences brain systems, both during intoxication and after years of chronic heavy use.Their findings can help identify mechanism-based therapeutic and pharmacological treatment options, and they may increase the efficacy and cost effectiveness of such treatments by predicting those at greatest risk for relapse.
View details for DOI 10.1111/j.1530-0277.2012.01831.x
View details for Web of Science ID 000312131400001
White matter fiber compromise contributes differentially to attention and emotion processing impairment in alcoholism, HIV-infection, and their comorbidity
2012; 50 (12): 2812-2822
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
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
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
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
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
Synchrony of Corticostriatal-Midbrain Activation Enables Normal Inhibitory Control and Conflict Processing in Recovering Alcoholic Men
2012; 71 (3): 269-278
View details for DOI 10.1016/j.biopsych.2011.10.022
View details for Web of Science ID 000299010900014
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
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
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
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
Cerebral blood flow in posterior cortical nodes of the default mode network decreases with task engagement but remains higher than in most brain regions.
2011; 21 (1): 233-244
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
Cerebral Blood Flow in Posterior Cortical Nodes of the Default Mode Network Decreases with Task Engagement but Remains Higher than in Most Brain Regions
2011; 21 (1): 233-244
View details for DOI 10.1093/cercor/bhq090
View details for Web of Science ID 000209071100001
White Matter Fiber Degradation Attenuates Hemispheric Asymmetry When Integrating Visuomotor Information
JOURNAL OF NEUROSCIENCE
2010; 30 (36): 12168-12178
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
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
Contribution of Callosal Connections to the Interhemispheric Integration of Visuomotor and Cognitive Processes
2010; 20 (2): 174-190
In recent years, cognitive neuroscience has been concerned with the role of the corpus callosum and interhemispheric communication for lower-level processes and higher-order cognitive functions. There is empirical evidence that not only callosal disconnection but also subtle degradation of the corpus callosum can influence the transfer of information and integration between the hemispheres. The reviewed studies on patients with callosal degradation with and without disconnection indicate a dissociation of callosal functions: while anterior callosal regions were associated with interhemispheric inhibition in situations of semantic (Stroop) and visuospatial (hierarchical letters) competition, posterior callosal areas were associated with interhemispheric facilitation from redundant information at visuomotor and cognitive levels. Together, the reviewed research on selective cognitive functions provides evidence that the corpus callosum contributes to the integration of perception and action within a subcortico-cortical network promoting a unified experience of the way we perceive the visual world and prepare our actions.
View details for DOI 10.1007/s11065-010-9130-1
View details for Web of Science ID 000278470400006
View details for PubMedID 20411431
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
Callosal degradation in HIV-1 infection predicts hierarchical perception: A DTI study
2010; 48 (4): 1133-1143
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
Neurocircuitry of emotion and cognition in alcoholism: contributions from white matter fiber tractography.
Dialogues in clinical neuroscience
2010; 12 (4): 554-560
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
Double dissociation between action-driven and perception-driven conflict resolution invoking anterior versus posterior brain systems
2009; 48 (2): 381-390
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
Parallel interhemispheric processing in hemineglect: Relation to visual field defects
2009; 47 (12): 2397-2408
Parallel interhemispheric processing is required to explore our visual environment and to integrate visual information from both hemifields simultaneously. Damage to the right temporo-parietal cortex can disrupt such parallel processes and result in neglect and visual extinction of stimuli in the left contralesional visual space. Neglected or extinguished stimuli can still be processed, yet without reaching the patient's awareness. Such unconscious processing has been attributed to structurally intact primary visual areas in neglect. To study whether unconscious parallel processing depends on visual functional integrity, we compared the performance of neglect patients with visual field defects (VFDs) (n=11) and hemianopic patients with partial or complete blindness of one visual hemifield (n=11) on redundant targets effects (RTE). The RTE manifests as faster reaction times to redundant paired (two stimuli, one in each hemifield) than single stimulation (in one hemifield). We found RTEs, i.e., unconscious processing, in neglect patients but not in hemianopic patients. Furthermore, neglect patients showed large crossed-uncrossed differences (CUDs), i.e., faster response times to ipsi- than contralesional hemifield stimulation, reflecting a difference in processing speed for single stimuli in the two hemispheres that were correlated with VFDs and visual extinction. The finding that extinction, but not RTE, was correlated with the CUD suggests that under competitive bilateral stimulus conditions the delayed contralesional visual field input may not be detected by the intact left hemisphere, which presumably mediates the task given the impairment of the right hemisphere. By contrast, unconscious parallel processing of contralesional stimuli (RTE) occurred even when contralesional visual field input is lacking (VFD) or delayed (CUD) and is possibly mediated via subcortical visual pathways.
View details for DOI 10.1016/j.neuropsychologia.2009.04.014
View details for Web of Science ID 000268864000006
View details for PubMedID 19393255
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
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
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
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
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
The topography of training-induced visual field recovery: Perimetric maps and subjective representations
2008; 16 (8): 1059-1077
View details for DOI 10.1080/13506280701566648
View details for Web of Science ID 000260797500004
Local-global interference is modulated by age, sex and anterior corpus callosum size
2007; 1142: 189-205
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
Vision restoration therapy does not benefit from costimulation: A pilot study
JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY
2007; 29 (6): 569-584
Visual field deficits in patients have long been considered to be nontreatable, but in previous studies we have found an enlargement of the intact visual field following vision restoration therapy (VRT). In the present pilot study, we wished to determine whether a double-stimulation approach would facilitate visual field enlargements beyond those achieved by the single-stimulus paradigm used in standard VRT. This was motivated by the findings that following visual cortex injury in animals, the size of receptive fields could be enlarged by systematic costimulation, where two stimuli were used to excite visual cortex neurons (Eysel, Eyding, & Schweigart, 1998). Patients (n = 23) with stable homonymous field deficits after trauma, cerebral ischemia, or hemorrhage (lesion age > 6 months) carried out either (a) standard VRT with a single stimulation (n = 9), or vision therapy with (b) a parallel costimulation (n = 7) or (c) a moving costimulation paradigm (n = 7). Training was carried out twice daily for 30 min over a 3-month period. Before and after therapy, visual fields were tested with 30 degrees and 90 degrees Tübinger automatic perimetry (TAP) and with high-resolution perimetry (HRP). Eye movements were recorded with an eye tracking system. When data of all three types of visual field training were pooled, we found significant improvements of stimulus detection in HRP (4.2%) and fewer misses within the central 30 degrees perimetrically (-3.7% right eye, OD, or -4.4% left eye, OS). However, the type of training did not make any difference such that the three training groups profited equally. A more detailed analysis of trained versus untrained visual field areas in 16 patients revealed a superiority of the trained area of only 1.1% in HRP and between 3.5% (OS) and 4.4% (OD) in TAP. Spatial attention and alertness improved significantly in all three groups and correlated significantly with visual field enlargements. While vision training had no influence on the patient's testimonials concerning their visual abilities, the patients significantly improved in a practical paper-and-pencil number tracking task (Zahlen-Verbindungs Test; ZVT). Visual field enlargement does not benefit from a double-stimulation paradigm, but visual attention seems to play an important role in vision restoration. The improvements in trained as well as in untrained areas are explained by top-down attentional control mechanisms interacting with local visual cortex plasticity.
View details for DOI 10.1080/13803390600878919
View details for Web of Science ID 000249358500001
View details for PubMedID 17691030
Visual hallucinations during spontaneous and training-induced visual field recovery
2007; 45 (11): 2598-2607
Visual hallucinations after post-geniculate visual system lesions were shown to be associated with spontaneous recovery of visual functions. We investigated the occurrence of hallucinations during spontaneous recovery and additionally tested whether hallucinations were re-instated in a phase of vision restoration therapy (VRT). Nineteen patients with post-geniculate lesions and homonymous visual loss participated in a prospective study, and 121 patients with various lesions were included in a retrospective study using a questionnaire including verbal descriptions as well as drawings of hallucinations experienced by the patients. In both samples, visual-field size was determined before and after 6 months of VRT. Many patients in both groups experienced post-lesion hallucinations (mostly colors, objects, motion) which subsided after spontaneous recovery of visual functions (increase of visual field size, recovery of more complex visual function) was ended. Hallucinations re-emerged during training. However, the majority of patients reported simple, unformed visual hallucinations (uncolored phosphenes, spots, flashes), especially when visual field recovery was most intense. Hallucinations were mainly found in patients with large shifts of the visual field border. They occurred in blind areas, particularly in areas of residual vision where recovery was predominantly observed. Hallucinations may reflect functional recovery in partially lesioned brain areas. While the colored/formed hallucinations during spontaneous recovery may represent non-specific activation of higher visual areas, the simple, unformed training-related hallucinations may indicate recovery in the primary visual cortex during treatment. Hallucinations should not generally be discarded as pathological or unimportant symptoms, but they may be functional indicators of visual system plasticity.
View details for DOI 10.1016/j.neuropsychologia.2007.03.005
View details for Web of Science ID 000247865800020
View details for PubMedID 17433383
Callosal involvement in a lateralized Stroop task in alcoholic and healthy subjects
2006; 20 (6): 727-736
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 10.1037/0894-422.214.171.1247
View details for Web of Science ID 000241761000011
View details for PubMedID 17100517
Improving residual vision by attentional cueing in patients with brain lesions
2006; 1097: 142-148
Visual attention is crucial for almost all processes of visual perception, particularly when perception is difficult. We were interested in the effects of cueing spatial attention in patients with cerebral lesions who face difficulties in visual perception in areas of residual vision at the border of visual field defects. In 23 patients with visual field loss due to post-geniculate brain lesions, stimulus detection performance and reaction times were mapped with high-resolution computer-based perimetry. A cueing procedure using Gestalt completion to attract attention to areas of residual vision was implemented in this test and performance compared in attended and unattended conditions. Stimulus detection and reaction times in areas of residual vision improved significantly under attended conditions. The extent of this effect depended on the size of areas of residual vision within the cued field. Unexpectedly, facilitation was also observed, though to a lesser extent, in invalid cueing conditions, suggesting an unspecific increase of alertness in unattended areas. Our findings show that top-down influences are relevant for visual field testing. Visuo-spatial attention may change patterns of neural activation and induce short-term plasticity not only in the intact visual system but also in the presence of visual field loss after brain lesions. Attentional cueing induces a co-activation of the lesioned visual system and (intact) attentional networks in the brain inducing immediate facilitation of visual perception. This effect may be relevant for designing new strategies to permanently improve vision during neuropsychological rehabilitation.
View details for DOI 10.1016/j.brainres.2006.04.011
View details for Web of Science ID 000239292000019
View details for PubMedID 16777076
FMRI evidence for individual differences in premotor modulation of extrastriatal visual-perceptual processing of redundant targets
2006; 30 (3): 973-982
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
Corpus callosal microstructural integrity influences interhemispheric processing: A diffusion tensor imaging study
2005; 15 (9): 1384-1392
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
Differential effect of HIV infection and alcoholism on conflict processing, attentional allocation, and perceptual load: Evidence from a Stroop Match-to-Sample task
2005; 57 (1): 67-75
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
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
Neglect and hemianopia superimposed
JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY
2003; 25 (8): 1154-1168
In patients with posterior-parietal brain damage it is often difficult to decide whether left-sided omissions in perimetry are due to primary visual loss or due to visual neglect. We investigated 11 patients with combined neglect/hemianopia and 11 patients with pure hemianopia using a visual search task with single or double stimulation conditions. The second stimulus was either the fixation point itself (like in perimetry) or a distractor appearing in the hemifield opposite to the target. The fixation point did not worsen left-sided perception, but its disappearance led to a bias of exploration towards the right side in neglect patients but not in pure hemianopics. A distractor in the intact hemifield worsened the performance to left-sided stimuli, that is, neglect patients behaved as if they were completely hemianopic, even in intact parts of the visual field (VF). Three of the neglect patients showed unconscious processing of the distractor in the left VF, suggesting that the visual field defect was produced by neglect mechanisms rather than primary visual loss. This visual search paradigm appears to be helpful in understanding of the nature of hemianopia versus neglect deficits in individual patients.
View details for Web of Science ID 000186631900010
View details for PubMedID 14566587
Patterns of visual field recovery: Decrease of defect size in perimetry and of subjective scotoma size in patients with cerebral lesions performing visual restitution training
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology
ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U1047–U1047
View details for Web of Science ID 000184606700955
Acute moderate alcohol consumption affects cardiovascular responses in healthy males with different tolerance levels
2002; 45 (4): 191-198
We investigated the effect of acute moderate alcohol consumption or placebo on respiratory sinus arrhythmia (RSA) in 48 healthy participants with different levels of alcohol tolerance but no abuse. In the electrocardiogram recording, auditory stimuli were presented at defined points in the respiratory cycle, which allows a non-invasive measure of CNS control over RSA. After alcohol consumption we found a decrease in RSA with auditory stimulation. Moreover, individuals with low tolerance showed only a slight change in the RSA after alcohol intake compared to baseline, whereas the placebo drink led to a reduced RSA. In subjects with high alcohol tolerance, alcohol consumption led to a reduction of RSA, with no change after placebo. These results suggest a centrally driven influence on RSA that is changed by alcohol ingestion depending upon subjects' levels of alcohol tolerance.
View details for Web of Science ID 000176986700006
View details for PubMedID 12097808
Unusual spontaneous and training induced visual field recovery in a patient with a gunshot lesion
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
2001; 70 (2): 236-239
Over a period of more than 3 years, changes in visual and neuropsychological functions were examined in a patient with a visual field defect caused by a cerebral gunshot lesion. Initially, the patient had been completely blind, but after 6 months of spontaneous recovery, he showed a homonymous bilateral lower quadrantanopia and impairment of higher visual functions. Unexpectedly, recovery still continued after the first 6 months. This process was documented in detail by visual field examinations using high resolution perimetry. When visual field size had stabilised almost 16 months after the lesion, further improvement could be achieved by visual restitution training. The duration and extent of spontaneous recovery were unusual. In spontaneous as well as in training induced recovery, progress was mainly seen in partially defective areas (areas of residual vision) along the visual field border. Thus, it is speculated that modulation of perceptual thresholds in transition zones of visual field defects contributes to spontaneous and training induced recovery.
View details for Web of Science ID 000166610500019
View details for PubMedID 11160476
Acute effects of alcohol on divided and covert attention in men
2001; 154 (1): 61-69
While several studies identified divided attention to be sensitive to alcohol effects, the impact of alcohol on covert visual attention is still not clear, despite the latter's important role in perception.The study tests the effect of acute moderate doses of alcohol on divided and covert attention in right-handed, male volunteers.The design of the study involved a double-blind trial with an alcohol and a placebo condition; measurements were taken before and after an oral dose of 0.6 g/kg alcohol versus placebo. In the divided-attention task, simultaneous visuo-spatial and auditory stimulation was applied. In a test of covert attention, subjects had to shift their attentional focus according to a central cue, from one location in the visual field to another.Under the divided-attention condition, reaction times were significantly prolonged after alcohol ingestion compared to placebo. Covert attention pre-post change was also significantly different between the alcohol and placebo groups. There is a reduction of false-cueing disturbance for left-appearing stimuli under moderate alcohol but an increase of disturbance for rightward stimuli, i.e. we found a lateralised pattern of reaction for spatial orienting. In the placebo group, no significant differences in right-left performance were obtained.The results suggest that sensory-attentional mechanisms play a key role in altered visual perceptual performance after alcohol ingestion. Furthermore, differences between the right and left visual field in the cued target-detection task indicate that alcohol exerts an influence on right-hemispheric attentional priming.
View details for Web of Science ID 000167350400009
View details for PubMedID 11292007
Restoration of vision II: Residual functions and training-induced visual field enlargement in brain-damaged patients
Workshop on Visual System Damage - Residual Functio n and Plasticity
IOS PRESS. 1999: 273–87
Brain damage is often accompanied by visual field defects which have been considered to be non-treatable. In recent years, however, new diagnostic methods have revealed hitherto unknown residual vision, which was found, for instance, in transition zones near the blind visual field sectors and in spared islands of vision within the blind regions ("blindsight"). Furthermore, animal studies revealed a high degree of plasticity in the visual system suggesting the possibility that recovery of vision may be induced by systematic visual training.Here we summarize a series of studies with patients suffering from visual field defects after brain lesion using some most recently developed computer-based programs for the diagnosis and treatment of visual field defects. Specifically, high-resolution perimetry (HRP) was applied to first diagnose residual function in or near the "blind" sector of the visual field. Thereafter, visual restitution training (VRT, see Kasten et al., Nature med. 4, 1998, p. 1083) was used daily for 6 months to provide systematic stimulation of these areas of residual vision.In a number of studies, we have observed not only residual visual functions within or near the field defect, but we were also able to follow the course of spontaneous recovery of visual functions within weeks or months after visual system damage. Furthermore, even long after spontaneous recovery is complete, computer-based visual restitution training (VRT) in or near the areas of residual vision results in a significant enlargement of intact areas, both after optic nerve damage and postchiasmatic lesions. Using VRT, we found a border shift of about 5 degrees of visual angle which cannot be explained by eye movements or eccentric fixation. We observed a transfer of this training effects to other tasks such as form and color detection, as well as to tests of visual exploration which were not specifically trained. Moreover, 72 % of the patients reported subjective improvements of vision. Training-induced visual field enlargement persisted for at least one year, even in the absence of training beyond 6 months of treatment.The visual system possesses a remarkable plasticity which becomes apparent in visual field enlargement during spontaneous recovery and specific visual training. Animal studies indicate that a minimum number of residual neurons surviving the lesion, in the order of 10%, provides a sufficient substrate for recovery of vision. Though the precise mechanisms of training-induced visual field enlargement need to be further explored, VRT can be introduced for routine clinical treatment of patients with visual field defects.
View details for Web of Science ID 000084922600015
View details for PubMedID 12671238