Gayle Deutsch, PhD, ABPP

All Publications

• Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder (vol 102, e207965, 2024) NEUROLOGY Vlahovic, L., McDonald, J., Hinman, J., Tomczak, A., Lock, C., Palmer, C. A., Cook, L. J., Yeaman, M. R., Burnett, M. K., Deutsch, G. K., Nelson, L. M., Han, M. H., CIRCLES Study Grp 2024; 103 (3)

  View details for DOI 10.1212/WNL.0000000000209215

  View details for Web of Science ID 001262358400001

• Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease. Acta neuropathologica Rutledge, J., Lehallier, B., Zarifkar, P., Losada, P. M., Shahid-Besanti, M., Western, D., Gorijala, P., Ryman, S., Yutsis, M., Deutsch, G. K., Mormino, E., Trelle, A., Wagner, A. D., Kerchner, G. A., Tian, L., Cruchaga, C., Henderson, V. W., Montine, T. J., Borghammer, P., Wyss-Coray, T., Poston, K. L. 2024; 147 (1): 52

  Abstract

  Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography-mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as L-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research.

  View details for DOI 10.1007/s00401-024-02706-0

  View details for PubMedID 38467937

  View details for PubMedCentralID 3995906

• Intracranial recordings of the human orbitofrontal cortical activity during self-referential episodic and valenced self-judgments. The Journal of neuroscience : the official journal of the Society for Neuroscience Iravani, B., Kaboodvand, N., Stieger, J. R., Liang, E. Y., Lusk, Z., Fransson, P., Deutsch, G. K., Gotlib, I. H., Parvizi, J. 2024

  Abstract

  We recorded directly from the orbital (oPFC) and ventromedial (vmPFC) subregions of the orbitofrontal cortex (OFC) in 22 (9 female, 13 male) epilepsy patients undergoing intracranial electroencephalography (iEEG) monitoring during an experimental task in which the participants judged the accuracy of self-referential autobiographical statements as well as valenced self-judgments. We found significantly increased high-frequency activity (HFA) in about 13% of oPFC sites (10/18 subjects) and 16% of vmPFC sites (4/12 subjects) during both of these self-referential thought processes, with the HFA power being modulated by the content of self-referential stimuli. The location of these activated sites corresponded with the location of fMRI-identified limbic network. Furthermore, the onset of HFA in the vmPFC was significantly earlier than in the oPFC in all patients with simultaneous recordings in both regions. In 11 patients with available depression scores from comprehensive neuropsychological assessments, we documented diminished HFA activity in the OFC during positive self-judgment trials among individuals with higher depression scores; responses during negative self-judgment trials were not related to the patients' depression scores. Our findings provide new temporal and anatomical information about the mode of engagement in two important subregions of the OFC during autobiographical memory and self-judgment conditions. Our findings from the OFC support the hypothesis that diminished brain activity during positive self-evaluations, rather than heightened activity during negative self-evaluations, plays a key role in the pathophysiology of depression.Significance Statement In direct recordings from the human brain, we observed significant responses characterized by high-frequency activity, aka high gamma, in distinct populations of the orbital (oPFC) and ventromedial (vmPFC) regions of the orbitofrontal cortex (OFC) - corresponding to the location of the resting state limbic network and to a lesser extent default mode network - when human subjects were engaged in self-referential episodic memory retrieval and self-trait judgments. Notably, simultaneous recordings across the two OFC regions in the same individuals revealed earlier activations in vmPFC than oPFC, indicating that the two subregions are involved in different stages of self-referential thought processes. Lastly, in individuals with high depressive symptoms, the OFC responses were significantly reduced during positive self-judgments but not heightened during negative self-evaluations.

  View details for DOI 10.1523/JNEUROSCI.1634-23.2024

  View details for PubMedID 38316564

• Learning Spectral Fractional Anisotropy and Mean Diffusivity Features as Neuroimaging Biomarkers for Tracking White Matter Integrity Changes in Myotonic Dystrophy Type 1 Patients using Deep Convolutional Neural Networks. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Kamali, T., Day, J. W., Deutsch, G. K., Sampson, J. B., Murad, A., Chaufty, J., Parker, D., Wozniak, J. R. 2023; 2023: 1-4

  Abstract

  Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular progressive multisystem disease that results in a broad spectrum of clinical central nervous system (CNS) involvement, including problems with memory, attention, executive functioning, and social cognition. Fractional anisotropy and mean diffusivity along-tract data calculated using diffusion tensor imaging techniques play a vital role in assessing white matter microstructural changes associated with neurodegeneration caused by DM1. In this work, a novel spectrogram-based deep learning method is proposed to characterize white matter network alterations in DM1 with the goal of building a deep learning model as neuroimaging biomarkers of DM1. The proposed method is evaluated on fractional anisotropies and mean diffusivities along-tract data calculated for 25 major white matter tracts of 46 DM1 patients and 96 unaffected controls. The evaluation data consists of a total of 7100 spectrogram images. The model achieved 91% accuracy in identifying DM1, a significant improvement compared to previous methods.Clinical relevance- Clinical care of DM1 is particularly challenging due to DM1 multisystem involvement and the disease variability. Patients with DM1 often experience neurological and psychological symptoms, such as excessive sleepiness and apathy, that greatly impact their quality of life. Some of DM1 CNS symptoms may be responsive to treatment. The goal of this research is to gain a deeper understanding of the impact of DM1 on the CNS and to develop a deep learning model that can serve as a biomarker for the disease, with the potential to be used in future clinical trials as an outcome measure.

  View details for DOI 10.1109/EMBC40787.2023.10340468

  View details for PubMedID 38083393

• Long-Term Cognitive and Neuropsychiatric Outcomes in Adults Who Have Received Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Aggressive Lymphoma at Stanford - a Pilot Feasibility Study Scott, B. J., Murray, T., Deutsch, G. K., Lahijani, S., Frank, M. J., Monje, M. AMER SOC HEMATOLOGY. 2022: 5201-5202

  View details for DOI 10.1182/blood-2022-168229

  View details for Web of Science ID 000893223205100

• Cognitive Impairment Analysis of Myotonic Dystrophy via Weakly Supervised Classification of Neuropsychological Features. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Kamali, T., Deutsch, G. K., Hagerman, K. A., Parker, D., Day, J. W., Sampson, J. B., Wozniak, J. R. 2022; 2022: 4377-4382

  Abstract

  The myotonic dystrophies (DM1 and DM2) are dominantly inherited disorders that cause pathological changes throughout the body. Many individuals with DM experience cognitive, behavioral and other functional central nervous system effects that impact their quality of life. The extent of psychological impairment that will develop in each patient is variable and unpredictable. Hence, it is difficult to get strong supervision information like fully ground truth labels for all cognitive involvement patterns. This study is to assess cognitive involvement among healthy controls and patients with DM. The DM cognitive impairment pattern observation is modeled in a weakly supervised setting and supervision information is used to transform the input feature space to a more discriminative representation suitable for pattern observation. This study incorporated results from 59 adults with DM and 92 control subjects. The developed system categorized the neuropsychological testing data into five cognitive clusters. The quality of the obtained clustering solution was assessed using an internal validity metric. The experimental results show that the proposed algorithm can discover interesting patterns and useful information from neuropsychological data, which will be be crucial in planning clinical trials and monitoring clinical performance. The proposed system resulted in an average classification accuracy of 88%, which is very promising considering the unique challenges present in this population.

  View details for DOI 10.1109/EMBC48229.2022.9871626

  View details for PubMedID 36086274

• Brief assessment of cognitive function in myotonic dystrophy: multicenter longitudinal study using computer-assisted evaluation. Muscle & nerve Deutsch, G. K., Hagerman, K. A., Sampson, J., Dent, G., Dekdebrun, J., Parker, D. M., Thornton, C. A., Heatwole, C. R., Subramony, S. H., Mankodi, A. K., Ashizawa, T., Statland, J. M., Arnold, W. D., Moxley, R. T., Day, J. W. 2022

  Abstract

  Myotonic dystrophy type 1 (DM1) is known to affect cognitive function, but the best methods to assess CNS involvement in multicenter studies have not been determined. This study's primary aim was to evaluate the potential of computerized cognitive tests to assess cognition in DM1.We conducted a prospective, longitudinal, observational study of 113 adults with DM1 at 6 sites. Psychomotor speed, attention, working memory, and executive functioning were assessed at baseline, 3-months and 12-months using computerized cognitive tests. Results were compared with assessments of muscle function and patient reported outcomes (PROs), including the Myotonic Dystrophy Health Index (MDHI) and EQ-5D-5L.Based on intra-class correlation coefficients (ICCs), computerized cognitive tests had moderate to good reliability for psychomotor speed (0.76), attention (0.82), working memory speed (0.79), working memory accuracy (0.65), and executive functioning (0.87). Performance at baseline was lowest for working memory accuracy (p < 0.0001). Executive function performance improved from baseline to 3-months (p < 0.0001), without further changes over one year. There was a moderate correlation between poorer executive function and larger CTG repeat size (r = -0.433). There were some weak associations between PROs and cognitive performance.Computerized tests of cognition are feasible in multicenter studies of DM1. Poor performance was exhibited in working memory, which may be a useful variable in clinical trials. Learning effects may have contributed to the improvement in executive functioning. The relationship between PROs and cognitive impairment in DM1 requires further study. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/mus.27520

  View details for PubMedID 35179228

• Association of CSF Biomarkers with Hippocampal-dependent Memory in Preclinical Alzheimer Disease. Neurology Trelle, A. N., Carr, V. A., Wilson, E. N., Swarovski, M. S., Hunt, M. P., Toueg, T. N., Tran, T. T., Channappa, D. n., Corso, N. K., Thieu, M. K., Jayakumar, M. n., Nadiadwala, A. n., Guo, W. n., Tanner, N. J., Bernstein, J. D., Litovsky, C. P., Guerin, S. A., Khazenzon, A. M., Harrison, M. B., Rutt, B. K., Deutsch, G. K., Chin, F. T., Davidzon, G. A., Hall, J. N., Sha, S. J., Fredericks, C. A., Andreasson, K. I., Kerchner, G. A., Wagner, A. D., Mormino, E. C. 2021

  Abstract

  To determine if memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer's disease (AD) biomarkers, we examined associations between performance in three memory tasks and CSF Aβ42/Aβ40 and p-tau181 in cognitively unimpaired older adults (CU).CU enrolled in the Stanford Aging and Memory Study (N=153; age 68.78 ± 5.81 yrs; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and phosopho-tau181 (p-tau181) were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied 'target' objects, novel 'foil' objects, and perceptually similar 'lure' objects. Analyses examined cross-sectional relationships between memory performance, age, and CSF measures, controlling for sex and education.Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with a) poorer associative memory and b) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but non-significant. CSF Aβ42 was not significantly associated with p-tau181 or memory.Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU, and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying cognitively unimpaired older adults with preclinical AD pathology.

  View details for DOI 10.1212/WNL.0000000000011477

  View details for PubMedID 33408146

• Toward Developing Robust Myotonic Dystrophy Brain Biomarkers using White Matter Tract Profiles Sub-Band Energy and A Framework of Ensemble Predictive Learning. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Kamali, T., Parker, D., Day, J. W., Sampson, J., Deutsch, G. K., Wozniak, J. R. 2021; 2021: 3838-3841

  Abstract

  The myotonic dystrophies (DM1 and DM2) are dominantly inherited disorders that cause pathological changes throughout the body and the brain. DM patients have difficulties with memory, attention, executive functioning, social cognition, and visuospatial function. Quantifying and understanding diffusion measures along main brain white matter fiber tracts offer a unique opportunity to reveal new insights into DM development and characterization. In this work, a novel supervised system is proposed, which is based on Tract Profiles sub-band energy information. The proposed system utilizes a Bayesian stacked random forest to diagnose, characterize, and predict DM clinical outcomes. The evaluation data consists of fractional anisotropies calculated for twelve major white matter tracts of 96 healthy controls and 62 DM patients. The proposed system discriminates DM vs. control with 86% accuracy, which is significantly higher than previous works. Additionally, it discovered DM brain biomarkers that are accurate and robust and will be helpful in planning clinical trials and monitoring clinical performance.

  View details for DOI 10.1109/EMBC46164.2021.9630544

  View details for PubMedID 34892071

• Safety of Plasma Infusions in Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society Parker, J. E., Martinez, A. n., Deutsch, G. K., Prabhakar, V. n., Lising, M. n., Kapphahn, K. I., Anidi, C. M., Neuville, R. n., Coburn, M. n., Shah, N. n., Bronte-Stewart, H. M. 2020

  Abstract

  Young plasma infusions have emerged as a potential treatment for neurodegenerative disease, and convalescent plasma therapy has been used safely in the management of viral pandemics. However, the effect of plasma therapy in Parkinson's disease (PD) is unknown.The objective of this study was to determine the safety, tolerability, and feasibility of plasma infusions in people with PD.A total of 15 people with clinically established PD, at least 1 cognitive complaint, and on stable therapy received 1 unit of young fresh frozen plasma twice a week for 4 weeks. Assessments and adverse effects were performed/reported on and off therapy at baseline, immediately after, and 4 weeks after the infusions ended. Adverse effects were also assessed during infusions. The primary outcomes were safety, tolerability, and feasibility. Exploratory outcomes included Unified Parkinson's Disease Rating Scale Part III off medication, neuropsychological battery, Parkinson's Disease Questionnaire-39, inflammatory markers (tumor necrosis factor-α, interleukin-6), uric acid, and quantitative kinematics.Adherence rate was 100% with no serious adverse effects. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson's Disease Questionnaire-39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor-α levels decreased 4 weeks after the infusions ended.Young fresh frozen plasma was safe, feasible, and well tolerated in people with PD, without serious adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. The results of this study warrant further therapeutic investigations in PD and provide safety and feasibility data for plasma therapy in people with PD who may be at higher risk for severe complications of COVID-19. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

  View details for DOI 10.1002/mds.28198

  View details for PubMedID 32633860

• Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults. eLife Trelle, A. N., Carr, V. A., Guerin, S. A., Thieu, M. K., Jayakumar, M. n., Guo, W. n., Nadiadwala, A. n., Corso, N. K., Hunt, M. P., Litovsky, C. P., Tanner, N. J., Deutsch, G. K., Bernstein, J. D., Harrison, M. B., Khazenzon, A. M., Jiang, J. n., Sha, S. J., Fredericks, C. A., Rutt, B. K., Mormino, E. C., Kerchner, G. A., Wagner, A. D. 2020; 9

  Abstract

  Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

  View details for DOI 10.7554/eLife.55335

  View details for PubMedID 32469308

• Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases. European journal of nuclear medicine and molecular imaging Mormino, E. C., Toueg, T. N., Azevedo, C. n., Castillo, J. B., Guo, W. n., Nadiadwala, A. n., Corso, N. K., Hall, J. N., Fan, A. n., Trelle, A. N., Harrison, M. B., Hunt, M. P., Sha, S. J., Deutsch, G. n., James, M. n., Fredericks, C. A., Koran, M. E., Zeineh, M. n., Poston, K. n., Greicius, M. D., Khalighi, M. n., Davidzon, G. A., Shen, B. n., Zaharchuk, G. n., Wagner, A. D., Chin, F. T. 2020

  Abstract

  In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD).Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aβ+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum.SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aβ+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient.Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

  View details for DOI 10.1007/s00259-020-04923-7

  View details for PubMedID 32572562

• Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease. NeuroImage. Clinical La, C. n., Linortner, P. n., Bernstein, J. D., Ua Cruadhlaoich, M. A., Fenesy, M. n., Deutsch, G. K., Rutt, B. K., Tian, L. n., Wagner, A. D., Zeineh, M. n., Kerchner, G. A., Poston, K. L. 2019; 23: 101824

  Abstract

  Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life.We studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD.In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05).In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.

  View details for PubMedID 31054380

• Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease NEUROIMAGE-CLINICAL La, C., Linortner, P., Bernstein, J. D., Cruadhlaoich, M., Fenesy, M., Deutsch, G. K., Rutt, B. K., Tian, L., Wagner, A. D., Zeineh, M., Kerchner, G. A., Poston, K. L. 2019; 23

  View details for DOI 10.1016/j.nicl.2019.101824

  View details for Web of Science ID 000485804400029

• Learning Disabilities Handbook of Medical Neuropsychology Deutsch, G. K., Davis, R. N. Springer Science Media. 2019; 2nd
• Repetitive transcranial magnetic stimulation directed to a seizure focus localized by high-density EEG: A case report. Epilepsy & behavior case reports Fisher, R., Zhou, J., Fogarty, A., Joshi, A., Markert, M., Deutsch, G. K., Velez, M. 2018; 10: 47–53

  Abstract

  We demonstrate feasibility of using high-density EEG to map a neocortical seizure focus in conjunction with delivery of magnetic therapy. Our patient had refractory seizures affecting the left leg. A five-day course of placebo stimulation followed a month later by active rTMS was directed to the mapped seizure dipole. Active rTMS resulted in reduced EEG spiking, and shortening of seizure duration compared to placebo. Seizure frequency, however, improved similarly in both placebo and active treatment stages. rTMS-evoked EEG potentials demonstrated that a negative peak at 40 ms - believed to represent GABAergic inhibition - was enhanced by stimulation.

  View details for PubMedID 29984172

• Neurocognitive Disorders APA Handbook of Psychopathology Yutsis, M. M., Rosen, A., Deutsch, G. K. 2018
• Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial. JAMA neurology Sha, S. J., Deutsch, G. K., Tian, L. n., Richardson, K. n., Coburn, M. n., Gaudioso, J. L., Marcal, T. n., Solomon, E. n., Boumis, A. n., Bet, A. n., Mennes, M. n., van Oort, E. n., Beckmann, C. F., Braithwaite, S. P., Jackson, S. n., Nikolich, K. n., Stephens, D. n., Kerchner, G. A., Wyss-Coray, T. n. 2018

  Abstract

  Young mouse plasma restores memory in aged mice, but, to our knowledge, the effects are unknown in patients with Alzheimer disease (AD).To assess the safety, tolerability, and feasibility of infusions of young fresh frozen plasma (yFFP) from donors age 18 to 30 years in patients with AD.The Plasma for Alzheimer Symptom Amelioration (PLASMA) study randomized 9 patients under a double-blind crossover protocol to receive 4 once-weekly infusions of either 1 unit (approximately 250 mL) of yFFP from male donors or 250 mL of saline, followed by a 6-week washout and crossover to 4 once-weekly infusions of an alternate treatment. Patients and informants were masked to treatment and subjective measurements. After an open-label amendment, 9 patients received 4 weekly yFFP infusions only and their subjective measurements were unmasked. Patients were enrolled solely at Stanford University, a tertiary academic medical center, from September 2014 to December 2016, when enrollment reached its target. Eighteen consecutive patients with probable mild to moderate AD dementia, a Mini-Mental State Examination (score of 12 to 24 inclusive), and an age of 50 to 90 years were enrolled. Thirty-one patients were screened and 13 were excluded: 11 failed the inclusion criteria and 2 declined to participate.One unit of yFFP from male donors/placebo infused once weekly for 4 weeks.The primary outcomes were the safety, tolerability, and feasibility of 4 weekly yFFP infusions. Safety end point analyses included all patients who received the study drug/placebo.There was no difference in the age (mean [SD], 74.17 [7.96] years), sex (12 women [67%]), or baseline Mini-Mental State Examination score (mean [SD], 19.39 [3.24]) between the crossover (n = 9) and open-label groups (n = 9). There were no related serious adverse events. One patient discontinued participation because of urticaria and another because of an unrelated stroke. There was no statistically significant difference between the plasma (17 [94.4%]) and placebo (9 [100.0%]) cohorts for other adverse events, which were mild to moderate in severity. The most common adverse events in the plasma group included hypertension (3 [16.7%]), dizziness (2 [11.1%]), sinus bradycardia (3 [16.7%]), headache (3 [16.7%]), and sinus tachycardia (3 [16.7%]). The mean visit adherence (n = 18) was 86% (interquartile range, 87%-100%) and adherence, accounting for a reduction in the total visit requirement due to early patient discontinuation, was 96% (interquartile range, 89%-100%).The yFFP treatment was safe, well tolerated, and feasible. The study's limitations were the small sample size, short duration, and change in study design. The results warrant further exploration in larger, double-blinded placebo-controlled clinical trials.ClinicalTrials.gov Identifier: NCT02256306.

  View details for PubMedID 30383097

• Accuracy statistics in predicting Independent Activities of Daily Living (IADL) capacity with comprehensive and brief neuropsychological test batteries. Applied neuropsychology. Adult Karzmark, P. n., Deutsch, G. K. 2017: 1–9

  Abstract

  This investigation was designed to determine the predictive accuracy of a comprehensive neuropsychological and brief neuropsychological test battery with regard to the capacity to perform instrumental activities of daily living (IADLs). Accuracy statistics that included measures of sensitivity, specificity, positive and negative predicted power and positive likelihood ratio were calculated for both types of batteries. The sample was drawn from a general neurological group of adults (n = 117) that included a number of older participants (age >55; n = 38). Standardized neuropsychological assessments were administered to all participants and were comprised of the Halstead Reitan Battery and portions of the Wechsler Adult Intelligence Scale-III. A comprehensive test battery yielded a moderate increase over base-rate in predictive accuracy that generalized to older individuals. There was only limited support for using a brief battery, for although sensitivity was high, specificity was low. We found that a comprehensive neuropsychological test battery provided good classification accuracy for predicting IADL capacity.

  View details for DOI 10.1080/23279095.2017.1286347

  View details for PubMedID 28631986

• Influenza-associated global amnesia and hippocampal imaging abnormality. Neurocase Lopez, J., Lomen-Hoerth, C., Deutsch, G. K., Kerchner, G. A., Koshy, A. 2014; 20 (4): 446-451

  Abstract

  The acute phase of influenza infection is rarely associated with significant cognitive dysfunction. We describe a case of a 24 year-old man who developed global amnesia in the acute phase of influenza A infection. His deficits resolved over the course of several weeks. Transient abnormalities of diffusion and T2-weighted imaging were seen in the bilateral hippocampi. We review cerebral complications of influenza and discuss the possible role of previously proposed mechanisms in our patient's case.

  View details for DOI 10.1080/13554794.2013.791864

  View details for PubMedID 23697757

• APOE {varepsilon}4 worsens hippocampal CA1 apical neuropil atrophy and episodic memory. Neurology Kerchner, G. A., Berdnik, D., Shen, J. C., Bernstein, J. D., Fenesy, M. C., Deutsch, G. K., Wyss-Coray, T., Rutt, B. K. 2014; 82 (8): 691-697

  Abstract

  Using high-resolution structural MRI, we endeavored to study the relationships among APOE ε4, hippocampal subfield and stratal anatomy, and episodic memory.Using a cross-sectional design, we studied 11 patients with Alzheimer disease dementia, 14 patients with amnestic mild cognitive impairment, and 14 age-matched healthy controls with no group differences in APOE ε4 carrier status. Each subject underwent ultra-high-field 7.0-tesla MRI targeted to the hippocampus and neuropsychological assessment.We found a selective, dose-dependent association of APOE ε4 with greater thinning of the CA1 apical neuropil, or stratum radiatum/stratum lacunosum-moleculare (CA1-SRLM), a hippocampal subregion known to exhibit early vulnerability to neurofibrillary pathology in Alzheimer disease. The relationship between the ε4 allele and CA1-SRLM thinning persisted after controlling for dementia severity, and the size of other hippocampal subfields and the entorhinal cortex did not differ by APOE ε4 carrier status. Carriers also exhibited worse episodic memory function but similar performance in other cognitive domains compared with noncarriers. In a statistical mediation analysis, we found support for the hypothesis that CA1-SRLM thinning may link the APOE ε4 allele to its phenotypic effects on memory.The APOE ε4 allele segregated dose-dependently and selectively with CA1-SRLM thinning and worse episodic memory performance in a pool of older subjects across a cognitive spectrum. These findings highlight a possible role for this gene in influencing a critical hippocampal subregion and an associated symptomatic manifestation.

  View details for DOI 10.1212/WNL.0000000000000154

  View details for PubMedID 24453080

• Shared vulnerability of two synaptically-connected medial temporal lobe areas to age and cognitive decline: a seven tesla magnetic resonance imaging study. journal of neuroscience Kerchner, G. A., Bernstein, J. D., Fenesy, M. C., Deutsch, G. K., Saranathan, M., Zeineh, M. M., Rutt, B. K. 2013; 33 (42): 16666-16672

  Abstract

  The medial temporal lobe (MTL) is the first brain area to succumb to neurofibrillary tau pathology in Alzheimer's disease (AD). Postmortem human tissue evaluation suggests that this pathology propagates in an ordered manner, with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum lacunosum-moleculare (CA1-SRLM)-two monosynaptically connected structures-exhibiting selective damage. Here, we hypothesized that, if ERC and CA1-SRLM share an early vulnerability to AD pathology, then atrophy should occur in a proportional manner between the two structures. We tested this hypothesis in living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL microstructure. Among a pool of age-matched healthy controls and patients with amnestic mild cognitive impairment and mild AD, we found a significant correlation between ERC and CA1-SRLM size that could not be explained by global atrophy affecting the MTL. Of the various structures that contribute axons or dendrites into the CA1-SRLM neuropil, only ERC emerged as a significant predictor of CA1-SRLM size in a linear regression analysis. In contrast, other synaptically connected elements of the MTL did not exhibit size correlations. CA1-SRLM and ERC structural covariance was significant for older controls and not patients, whereas the opposite pattern emerged for a correlation between CA1-SRLM and episodic memory performance. Interestingly, CA1-SRLM and ERC were the only MTL structures to atrophy in older controls relative to a younger comparison group. Together, these findings suggest that ERC and CA1-SRLM share vulnerability to both age and AD-associated atrophy.

  View details for DOI 10.1523/JNEUROSCI.1915-13.2013

  View details for PubMedID 24133269

  View details for PubMedCentralID PMC3797378

• Hippocampal CA1 apical neuropil atrophy and memory performance in Alzheimer's disease NEUROIMAGE Kerchner, G. A., Deutsch, G. K., Zeineh, M., Dougherty, R. F., Saranathan, M., Rutt, B. K. 2012; 63 (1): 194-202

  Abstract

  Memory loss is often the first and most prominent symptom of Alzheimer's disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220 μm, allowing direct visual identification of subfields - dentate gyrus (DG)/CA3, CA2, CA1, and ERC - and hippocampal strata - SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r(2)=0.69; p=0.005), CA1-SP (r(2)=0.5; p=0.034), and ERC (r(2)=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD.

  View details for DOI 10.1016/j.neuroimage.2012.06.048

  View details for Web of Science ID 000308770300020

  View details for PubMedID 22766164

  View details for PubMedCentralID PMC3677969

• Comparison of the Frontal Systems Behavior Scale and Neuropsychological Tests of Executive Functioning in Predicting Instrumental Activities of Daily Living APPLIED NEUROPSYCHOLOGY Karzmark, P., Llanes, S., Tan, S., Deutsch, G., Zeifert, P. 2012; 19 (2): 81-85

  Abstract

  Both neuropsychological tests of executive functioning and the Frontal Systems Behavior Scale (FrSBe) consistently predict instrumental activity-of-daily-living capacity. However, the nature of the predictive relationship between the FrSBe and neuropsychological tests of executive functioning has received limited attention. The current study was designed to assess the incremental validity of the FrSBe in predicting instrumental activity-of-daily-living functioning when added to comprehensive testing of executive functioning in a sample of 100 adult general neuropsychological referrals. A composite measure of executive test performance was calculated, and a family member completed the FrSBe and an instrumental activity-of-daily-living measure. Stepwise multiple regression analysis using the executive composite measure and the FrSBe accounted for 44% of the variance in instrumental activity capacity, and the addition of the FrSBe increased predictive ability by approximately 50%. The current results also indicate that FrSBe Scale E is more important as a predictor of instrumental activity capacity than the two self-regulation measures, Scale A and Scale D.

  View details for DOI 10.1080/09084282.2011.643942

  View details for Web of Science ID 000304596100001

  View details for PubMedID 23373573

• Anatomical Properties of the Arcuate Fasciculus Predict Phonological and Reading Skills in Children JOURNAL OF COGNITIVE NEUROSCIENCE Yeatman, J. D., Dougherty, R. F., Rykhlevskaia, E., Sherbondy, A. J., Deutsch, G. K., Wandell, B. A., Ben-Shachar, M. 2011; 23 (11): 3304-3317

  Abstract

  For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.

  View details for Web of Science ID 000295869500011

  View details for PubMedID 21568636

• The Development of Cortical Sensitivity to Visual Word Forms JOURNAL OF COGNITIVE NEUROSCIENCE Ben-Shachar, M., Dougherty, R. F., Deutsch, G. K., Wandell, B. A. 2011; 23 (9): 2387-2399

  Abstract

  The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7-12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.

  View details for Web of Science ID 000292508900024

  View details for PubMedID 21261451

• Learning Disabilities Handbook of Medical Neuropsychology GK, D., RN, D. Springer. 2010
• Frontoparietal white matter diffusion properties predict mental arithmetic skills in children PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tsang, J. M., Dougherty, R. F., Deutsch, G. K., Wandell, B. A., Ben-Shachar, M. 2009; 106 (52): 22546-22551

  Abstract

  Functional MRI studies of mental arithmetic consistently report blood oxygen level-dependent signals in the parietal and frontal regions. We tested whether white matter pathways connecting these regions are related to mental arithmetic ability by using diffusion tensor imaging (DTI) to measure these pathways in 28 children (age 10-15 years, 14 girls) and assessing their mental arithmetic skills. For each child, we identified anatomically the anterior portion of the superior longitudinal fasciculus (aSLF), a pathway connecting parietal and frontal cortex. We measured fractional anisotropy in a core region centered along the length of the aSLF. Fractional anisotropy in the left aSLF positively correlates with arithmetic approximation skill, as measured by a mental addition task with approximate answer choices. The correlation is stable in adjacent core aSLF regions but lower toward the pathway endpoints. The correlation is not explained by shared variance with other cognitive abilities and did not pass significance in the right aSLF. These measurements used DTI, a structural method, to test a specific functional model of mental arithmetic.

  View details for DOI 10.1073/pnas.0906094106

  View details for Web of Science ID 000273178700090

  View details for PubMedID 19948963

  View details for PubMedCentralID PMC2799736

• Reading impairment in a patient with missing arcuate fasciculus NEUROPSYCHOLOGIA Rauschecker, A. M., Deutsch, G. K., Ben-Shachar, M., Schwartzman, A., Perry, L. M., Dougherty, R. F. 2009; 47 (1): 180-194

  Abstract

  We describe the case of a child ("S") who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.

  View details for DOI 10.1016/j.neuropsychologia.2008.08.011

  View details for Web of Science ID 000262614100020

  View details for PubMedID 18775735

  View details for PubMedCentralID PMC2671152

• Contrast responsivity in MT plus correlates with phonological awareness and reading measures in children NEUROIMAGE Ben-Shachar, M., Dougherty, R. F., Deutsch, G. K., Wandell, B. A. 2007; 37 (4): 1396-1406

  Abstract

  There are several independent sets of findings concerning the neural basis of reading. One set demonstrates a powerful relationship between phonological processing and reading skills. Another set reveals a relationship between visual responses in the motion pathways and reading skills. It is widely assumed that these two findings are unrelated. We tested the hypothesis that phonological awareness is related to motion responsivity in children's MT+. We measured BOLD signals to drifting gratings as a function of contrast. Subjects were 35 children ages 7-12 years with a wide range of reading skills. Contrast responsivity in MT+, but not V1, was correlated with phonological awareness and to a lesser extent with two other measures of reading. No correlation was found between MT+ signals and rapid naming, age or general IQ measures. These results establish an important link between visual and phonological processing in children and suggest that MT+ responsivity is a marker for healthy reading development.

  View details for DOI 10.1016/j.neuroimage.2007.05.060

  View details for Web of Science ID 000249773600043

  View details for PubMedID 17689981

  View details for PubMedCentralID PMC2034404

• Differential sensitivity to words and shapes in ventral occipito-temporal cortex CEREBRAL CORTEX Ben-Shachar, M., Dougherty, R. F., Deutsch, G. K., Wandell, B. A. 2007; 17 (7): 1604-1611

  Abstract

  Efficient extraction of shape information is essential for proficient reading but the role of cortical mechanisms of shape analysis in word reading is not well understood. We studied cortical responses to written words while parametrically varying the amount of visual noise applied to the word stimuli. In only a few regions along the ventral surface, cortical responses increased with word visibility. We found consistently increasing responses in bilateral posterior occipito-temporal sulcus (pOTS), at an anatomical location that closely matches the "visual word form area". In other cortical regions, such as V1, responses remained constant regardless of the noise level. We performed 3 additional tests to assess the functional specialization of pOTS responses for written word processing. We asked whether pOTS responses are 1) left lateralized, 2) more sensitive to words than to line drawings or false fonts, and 3) invariant for visual hemifield of words but not other stimuli. We found that left and right pOTS response functions both had highest sensitivity for words, intermediate for line drawings, and lowest for false fonts. Visual hemifield invariance was similar for words and line drawings. These results suggest that left and right pOTS are both involved in shape processing, with enhanced efficiency for processing visual word forms.

  View details for DOI 10.1093/cercor/bhl071

  View details for Web of Science ID 000247349000011

  View details for PubMedID 16956978

• Temporal-callosal pathway diffusivity predicts phonological skills in children PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dougherty, R. F., Ben-Shachar, M., Deutsch, G. K., Hernandez, A., Fox, G. R., Wandell, B. A. 2007; 104 (20): 8556-8561

  Abstract

  The development of skilled reading requires efficient communication between distributed brain regions. By using diffusion tensor imaging, we assessed the interhemispheric connections in a group of children with a wide range of reading abilities. We segmented the callosal fibers into regions based on their likely cortical projection zones, and we measured diffusion properties in these segmented regions. Phonological awareness (a key factor in reading acquisition) was positively correlated with diffusivity perpendicular to the main axis of the callosal fibers that connect the temporal lobes. These results could be explained by several physiological properties. For example, good readers may have fewer but larger axons connecting left and right temporal lobes, or their axon membranes in these regions may be more permeable than the membranes of poor readers. These measurements are consistent with previous work suggesting that good readers have reduced interhemispheric connectivity and are better at processing rapidly changing visual and auditory stimuli.

  View details for DOI 10.1073/pnas.0608961104

  View details for Web of Science ID 000246599900065

  View details for PubMedID 17483487

  View details for PubMedCentralID PMC1895988

• Functional and morphometric brain dissociation between dyslexia and reading ability PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Hoeft, F., Meyler, A., Hernandez, A., Juel, C., Taylor-Hill, H., Martindale, J. L., McMillon, G., Kolchugina, G., Black, J. M., Faizi, A., Deutsch, G. K., Siok, W. T., Reiss, A. L., Whitfield-Gabrieli, S., Gabrieli, J. D. 2007; 104 (10): 4234-4239

  Abstract

  In functional neuroimaging studies, individuals with dyslexia frequently exhibit both hypoactivation, often in the left parietotemporal cortex, and hyperactivation, often in the left inferior frontal cortex, but there has been no evidence to suggest how to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. To address this question, we measured brain activation by functional MRI during visual word rhyme judgment compared with visual cross-hair fixation rest, and we measured gray matter morphology by voxel-based morphometry in dyslexic adolescents in comparison with (i) an age-matched group, and (ii) a reading-matched group younger than the dyslexic group but equal to the dyslexic group in reading performance. Relative to the age-matched group (n = 19; mean 14.4 years), the dyslexic group (n = 19; mean 14.4 years) exhibited hypoactivation in left parietal and bilateral fusiform cortices and hyperactivation in left inferior and middle frontal gyri, caudate, and thalamus. Relative to the reading-matched group (n = 12; mean 9.8 years), the dyslexic group (n = 12; mean 14.5 years) also exhibited hypoactivation in left parietal and fusiform regions but equal activation in all four areas that had exhibited hyperactivation relative to age-matched controls as well. In regions that exhibited atypical activation in the dyslexic group, only the left parietal region exhibited reduced gray matter volume relative to both control groups. Thus, areas of hyperactivation in dyslexia reflected processes related to the level of current reading ability independent of dyslexia. In contrast, areas of hypoactivation in dyslexia reflected functional atypicalities related to dyslexia itself, independent of current reading ability, and related to atypical brain morphology in dyslexia.

  View details for DOI 10.1073/pnas.0609399104

  View details for Web of Science ID 000244972400100

  View details for PubMedID 17360506

  View details for PubMedCentralID PMC1820738

• Neural correlates of rapid auditory processing are disrupted in children with developmental dyslexia and ameliorated with training: An fMRI study RESTORATIVE NEUROLOGY AND NEUROSCIENCE Gaab, N., Gabrieli, J. D., Deutsch, G. K., Tallal, P., Temple, E. 2007; 25 (3-4): 295-310

  Abstract

  Developmental dyslexia, characterized by unexpected difficulty in reading, may involve a fundamental deficit in processing rapid acoustic stimuli. Using functional magnetic resonance imaging (fMRI) we previously reported that adults with developmental dyslexia have a disruption in neural response to rapid acoustic stimuli in left prefrontal cortex. Here we examined the neural correlates of rapid auditory processing in children.Whole-brain fMRI was performed on twenty-two children with developmental dyslexia and twenty-three typical-reading children while they listened to nonlinguistic acoustic stimuli, with either rapid or slow transitions, designed to mimic the spectro-temporal structure of consonant-vowel-consonant speech syllables.Typical-reading children showed activation for rapid compared to slow transitions in left prefrontal cortex. Children with developmental dyslexia did not show any differential response in these regions to rapid versus slow transitions. After eight weeks of remediation focused primarily on rapid auditory processing, phonological and linguistic training the children with developmental dyslexia showed significant improvements in language and reading skills, and exhibited activation for rapid relative to slow transitions in left prefrontal cortex.The presence of a disruption in the neural response to rapid stimuli in children with developmental dyslexia prior to remediation, coupled with significant improvement in language and reading scores and increased brain activation after remediation, gives further support to the importance of rapid auditory processing in reading development and disorders.

  View details for Web of Science ID 000251513800010

  View details for PubMedID 17943007

• Neural basis of dyslexia: A comparison between dyslexic and nondyslexic children equated for reading ability JOURNAL OF NEUROSCIENCE Hoeft, F., Hernandez, A., McMillon, G., Taylor-Hill, H., Martindale, J. L., Meyler, A., Keller, T. A., Siok, W. T., Deutsch, G. K., Just, M. A., Whitfield-Gabrieli, S., Gabrieli, J. D. 2006; 26 (42): 10700-10708

  Abstract

  Adults and children with developmental dyslexia exhibit reduced parietotemporal activation in functional neuroimaging studies of phonological processing. These studies used age-matched and/or intelligence quotient-matched control groups whose reading ability and scanner task performance were often superior to that of the dyslexic group. It is unknown, therefore, whether differences in activation reflect simply poorer performance in the scanner, the underlying level of reading ability, or more specific neural correlates of dyslexia. To resolve this uncertainty, we conducted a functional magnetic resonance imaging study, with a rhyme judgment task, in which we compared dyslexic children with two control groups: age-matched children and reading-matched children (younger normal readers equated for reading ability or scanner-performance to the dyslexic children). Dyslexic children exhibited reduced activation relative to both age-matched and reading-matched children in the left parietotemporal cortex and five other regions, including the right parietotemporal cortex. The dyslexic children also exhibited reduced activation bilaterally in the parietotemporal cortex when compared with children equated for task performance during scanning. Nine of the 10 dyslexic children exhibited reduced left parietotemporal activation compared with their individually selected age-matched or reading-matched control children. Additionally, normal reading fifth graders showed more activation in the same bilateral parietotemporal regions than normal-reading third graders. These findings indicate that the activation differences seen in the dyslexic children cannot be accounted for by either current reading level or scanner task performance, but instead represent a distinct developmental atypicality in the neural systems that support learning to read.

  View details for DOI 10.1523/JNEUROSCI.4931-05.2006

  View details for Web of Science ID 000241727300013

  View details for PubMedID 17050709

• Children's reading performance is correlated with white matter structure measured by diffusion tensor imaging CORTEX Deutsch, G. K., Dougherty, R. F., Bammer, R., Siok, W. T., Gabrieli, J. D., Wandell, B. 2005; 41 (3): 354-363

  Abstract

  We investigated the white matter structure in children (n = 14) with a wide range of reading performance levels using diffusion tensor imaging (DTI), a form of magnetic resonance imaging. White matter structure in a left temporo-parietal region that had been previously described as covarying with reading skill in adult readers also differs between children who are normal and poor readers. Specifically, the white matter structure measured using fractional anisotropy (FA) and coherence index (CI) significantly correlated with behavioral measurements of reading, spelling, and rapid naming performance. In general, lower anisotropy and lower coherence were associated with lower performance scores. Although the magnitude of the differences in children are smaller than those in adults, the results support the hypothesis that the structure of left temporoparietal neural pathways is a significant component of the neural system needed to develop fluent reading.

  View details for Web of Science ID 000228941100008

  View details for PubMedID 15871600

• Occipital-callosal pathways in children - Validation and atlas development Workshop on White Matter in the Cognitive Neurosciences Dougherty, R. F., Ben-Shachar, M., Deutsch, G., Potanina, P., Bammer, R., Wandell, B. A. NEW YORK ACAD SCIENCES. 2005: 98-?

  Abstract

  Diffusion tensor imaging and fiber tracking were used to measure fiber bundles connecting the two occipital lobes in 53 children of 7-12 years of age. Independent fiber bundle estimates originating from the two hemispheres converge onto the lower half of the splenium. This observation validates the basic methodology and suggests that most occipital-callosal fibers connect the two occipital lobes. Within the splenium, fiber bundles are organized in a regular pattern with respect to their cortical projection zones. Visual cortex dorsal to calcarine projects through a large band that fills much of the inferior half of the splenium, while cortex ventral to calcarine sends projections through a band at the anterior inferior edge of the splenium. Pathways projecting to the occipital pole and lateral-occipital regions overlap the dorsal and ventral groups slightly anterior to the center of the splenium. To visualize these pathways in a typical brain, we combined the data into an atlas. The estimated occipital-callosal fiber paths from the atlas form the walls of the occipital horn of the lateral ventricle, with dorsal paths forming the medial wall and the ventral paths bifurcating into a medial tract to form the inferior-medial wall and a superior tract that joins the lateral-occipital paths to form the superior wall of the ventricle. The properties of these fiber bundles match those of the hypothetical pathways described in the neurological literature on alexia.

  View details for DOI 10.1196/annals.1340.017

  View details for Web of Science ID 000235430200008

  View details for PubMedID 16394151

• Neural deficits in children with dyslexia ameliorated by behavioral remediation: Evidence from functional MRI PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Temple, E., Deutsch, G. K., Poldrack, R. A., Miller, S. L., Tallal, P., Merzenich, M. M., Gabrieli, J. D. 2003; 100 (5): 2860-2865

  Abstract

  Developmental dyslexia, characterized by unexplained difficulty in reading, is associated with behavioral deficits in phonological processing. Functional neuroimaging studies have shown a deficit in the neural mechanisms underlying phonological processing in children and adults with dyslexia. The present study examined whether behavioral remediation ameliorates these dysfunctional neural mechanisms in children with dyslexia. Functional MRI was performed on 20 children with dyslexia (8-12 years old) during phonological processing before and after a remediation program focused on auditory processing and oral language training. Behaviorally, training improved oral language and reading performance. Physiologically, children with dyslexia showed increased activity in multiple brain areas. Increases occurred in left temporo-parietal cortex and left inferior frontal gyrus, bringing brain activation in these regions closer to that seen in normal-reading children. Increased activity was observed also in right-hemisphere frontal and temporal regions and in the anterior cingulate gyrus. Children with dyslexia showed a correlation between the magnitude of increased activation in left temporo-parietal cortex and improvement in oral language ability. These results suggest that a partial remediation of language-processing deficits, resulting in improved reading, ameliorates disrupted function in brain regions associated with phonological processing and produces additional compensatory activation in other brain regions.

  View details for DOI 10.1073/pnas.0030098100

  View details for Web of Science ID 000181365000123

  View details for PubMedID 12604786

  View details for PubMedCentralID PMC151431

• Disrupted neural responses to phonological and orthographic processing in dyslexic children: an fMRI study NEUROREPORT Temple, E., Poldrack, R. A., Salidis, J., Deutsch, G. K., Tallal, P., Merzenich, M. M., Gabrieli, J. D. 2001; 12 (2): 299-307

  Abstract

  Developmental dyslexia, characterized by difficulty in reading, has been associated with phonological and orthographic processing deficits. fMRI was performed on dyslexic and normal-reading children (8-12 years old) during phonological and orthographic tasks of rhyming and matching visually presented letter pairs. During letter rhyming, both normal and dyslexic reading children had activity in left frontal brain regions, whereas only normal-reading children had activity in left temporo-parietal cortex. During letter matching, normal-reading children showed activity throughout extrastriate cortex, especially in occipito-parietal regions, whereas dyslexic children had little activity in extrastriate cortex during this task. These results indicate dyslexia may be characterized in childhood by disruptions in the neural bases of both phonological and orthographic processes important for reading.

  View details for Web of Science ID 000166702100024

  View details for PubMedID 11209939

• Hemispheric asymmetries in arousal affect outcome of the intracarotid amobarbital test NEUROLOGY Glosser, G., Cole, L. C., Deutsch, G. K., Donofrio, N., Bagley, L., Baltuch, G., French, J. A. 1999; 52 (8): 1583-1590

  Abstract

  To evaluate changes in arousal and their impact on memory performance during the intracarotid amobarbital test (IAT).Along with memory measures, level of arousal was evaluated through clinical ratings and nonverbal self-ratings in epilepsy patients undergoing IAT before anterior temporal lobectomy.Irrespective of seizure focus, left-sided amobarbital injection resulted in decreased objective and subjective arousal more often than right-side injection. Impaired objective arousal was greater when the left hemisphere was injected second, because of the presumed additive effects of systemic amobarbital residual from the first injection. Decreased objective arousal was related to poorer performance on memory testing following left-hemisphere injection.The IAT, as practiced in most centers, is biased, so patients with right temporal lobe seizure focus are more likely to "pass" the test, whereas patients with left seizure focus are more likely to "fail" the test. The significant impact of changes in arousal on memory testing needs to be considered when using IAT results to select patients for temporal lobectomy.

  View details for Web of Science ID 000080233600014

  View details for PubMedID 10331682

• Differential lateralization of memory discrimination and response bias in temporal lobe epilepsy patients JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Glosser, G., Deutsch, G. K., Cole, L. C., Corwin, J., Saykin, A. J. 1998; 4 (5): 502-511

  Abstract

  Recognition memory for words and designs was assessed in epilepsy patients who underwent unilateral anterior temporal lobectomy. Memory was assessed during the intracarotid amobarbital test (IAT) performed prior to surgery and also following surgery. Memory discrimination and response bias lateralized differently. Memory discrimination, or memory accuracy, lateralized as a function of the type of material used in memory testing. Left temporal lobe lesions resulted in more impaired discrimination of verbal materials; right temporal lobe lesions resulted in more impaired discrimination of visuospatial materials. Response bias, the decision rule adopted in situations of uncertainty, was more liberal following left temporal lobe lesions for both verbal and visuospatial materials. Findings suggest that the two cerebral hemispheres are differentially specialized for encoding different types of information in long term memory, and that this impacts on decision strategies in situations of memory uncertainty.

  View details for Web of Science ID 000076001000009

  View details for PubMedID 9745239

• Psychogenic events presenting as parasomnia SLEEP Molaie, M., Deutsch, G. K. 1997; 20 (6): 402-405

  Abstract

  A 10-year-old child suddenly developed nocturnal enuresis and nocturnal behaviors similar to parasomnia that were occasionally violent. The child had no recollection of the events. Continuous video/electroencephalograph monitoring revealed the episodic nocturnal events with bizarre behaviors during what was perceived to be sleep, but in fact, the child was fully awake with his eyes closed, prior to and during the events. The attacks ceased with individual psychotherapy and family counseling.

  View details for Web of Science ID A1997XX25300005

  View details for PubMedID 9302724

• Metamemory in temporal lobe epilepsy ASSESSMENT GK, D., AJ, S., MR, S. 1996; 3 (3): 255-263
• Reliability and construct validity of the Paired-Associate Recognition Memory Test: A test of declarative memory using Wisconsin Card Sorting stimuli PSYCHOLOGICAL ASSESSMENT JR, R., RE, G., GK, D., DM, C., RC 1995; 7: 25-32
• Patterns of reorganization of memory functions within and between cerebral hemispheres as assessed by the intracarotid amobarbital test NEUROPSYCHOLOGY G, G., AJ, S., GK, D., MR, S., MJ, O. 1995; 9 (4): 449-456