Clinical Focus

  • Psychology
  • Psychiatry

Honors & Awards

  • MRI Biomarkers of Mild Cognitive Impairment in Breast Cancer (R01), NINR (2012-2017)
  • Prefrontal Cortex Abnormalities Associated with Breast Cancer Chemotherapy (R01), NCI (2012-2017)
  • Neurobiologic Mechanisms of Cognitive Decline in Medulloblastoma (K07), NCI (2009-2014)
  • Assessment and Treatment of Cognitive Dysfunction in Breast Cancer (DP2), NIH Director's New Innovator Award (2008-2013)

Professional Education

  • Residency:Adolescent Residential Treatment and Evaluation Center (2001) UT
  • Medical Education:Brigham Young University (2003) UT
  • Internship:University of Utah Medical Center (2000) UT
  • PhD, BYU, Clinical Neuropsychology (2000)

Research & Scholarship

Current Research and Scholarly Interests

Dr. Shelli Kesler is an Assistant Professor and Clinical Neuropsychologist in the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine. Dr. Kesler’s academic research program focuses on the application of cognitive neuroscience to the study of clinical populations. Her laboratory seeks to identify the biological mechanisms underlying cognitive deficit, develop and implement novel behavioral interventions for cognitive dysfunction and improve cognitive neuroscience research methodology by introducing new tools for neuroimaging analyses.

Dr. Kesler is particularly interested in the neurotoxic effects of cancer, often referred to as “chemobrain”. She has helped advance this field of research by demonstrating that chemotherapy is associated with a pattern of subtle but diffuse brain injury. She has also introduced a novel, home-based cognitive training program for cancer survivors who are struggling with cognitive difficulties. She was a recipient of the NIH Director’s New Innovator Award in 2008 for her research in cognition and cancer. Dr. Kesler is unique in that her research and clinical practice involves both children and adults. She has authored over 50 scientific publications as well as the book “Improving Cognitive Function After Cancer” for lay readers.

Clinical Trials

  • Phase II Early Behavioral Intervention in BMT w/ Sleep Disturbance-Assess QOL+Fatigue+Cognitive f(x) Recruiting

    This pilot clinical trial studies early brief behavioral intervention in treating sleep disturbance and improving quality of life in patients undergoing bone marrow transplant (BMT). A brief behavioral intervention may reduce symptoms of insomnia and fatigue and improve quality of life and cognitive function in patients undergoing BMT

    View full details


2013-14 Courses


Journal Articles

  • Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy BRAIN IMAGING AND BEHAVIOR Kesler, S. R., Watson, C., Koovakkattu, D., Lee, C., O'Hara, R., Mahaffey, M. L., Wefel, J. S. 2013; 7 (4): 501-510


    Breast cancer survivors are at increased risk for cognitive dysfunction, which reduces quality of life. Neuroimaging studies provide critical insights regarding the mechanisms underlying these cognitive deficits as well as potential biologic targets for interventions. We measured several metabolite concentrations using (1)H magnetic resonance spectroscopy as well as cognitive performance in 19 female breast cancer survivors and 17 age-matched female controls. Women with breast cancer were all treated with chemotherapy. Results indicated significantly increased choline (Cho) and myo-inositol (mI) with correspondingly decreased N-acetylaspartate (NAA)/Cho and NAA/mI ratios in the breast cancer group compared to controls. The breast cancer group reported reduced executive function and memory, and subjective memory ability was correlated with mI and Cho levels in both groups. These findings provide preliminary evidence of an altered metabolic profile that increases our understanding of neurobiologic status post-breast cancer and chemotherapy.

    View details for DOI 10.1007/s11682-013-9228-1

    View details for Web of Science ID 000328853800010

    View details for PubMedID 23536015

  • Anomalous gray matter structural networks in major depressive disorder. Biological psychiatry Singh, M. K., Kesler, S. R., Hadi Hosseini, S. M., Kelley, R. G., Amatya, D., Hamilton, J. P., Chen, M. C., Gotlib, I. H. 2013; 74 (10): 777-785


    BACKGROUND: Major depressive disorder (MDD) is characterized by abnormalities in structure, function, and connectivity in several brain regions. Few studies have examined how these regions are organized in the brain or investigated network-level structural aberrations that might be associated with depression. METHODS: We used graph analysis to examine the gray matter structural networks of individuals diagnosed with MDD (n = 93) and a demographically similar healthy comparison group (n = 151) with no history of psychopathology. The efficiency of structural networks for processing information was determined by quantifying local interconnectivity (clustering) and global integration (path length). We also compared the groups on the contributions of high-degree nodes (i.e., hubs) and regional network measures, including degree (number of connections in a node) and betweenness (fraction of short path connections in a node). RESULTS: Depressed participants had significantly decreased clustering in their brain networks across a range of network densities. Compared with control subjects, depressed participants had fewer hubs primarily in medial frontal and medial temporal areas, had higher degree in the left supramarginal gyrus and right gyrus rectus, and had higher betweenness in the right amygdala and left medial orbitofrontal gyrus. CONCLUSIONS: Networks of depressed individuals are characterized by a less efficient organization involving decreased regional connectivity compared with control subjects. Regional connections in the amygdala and medial prefrontal cortex may play a role in maintaining or adapting to depressive pathology. This is the first report of anomalous large-scale gray matter structural networks in MDD and provides new insights concerning the neurobiological mechanisms associated with this disorder.

    View details for DOI 10.1016/j.biopsych.2013.03.005

    View details for PubMedID 23601854

  • Psychosocial predictors of treatment response to cognitive-behavior therapy for late-life depression: an exploratory study AGING & MENTAL HEALTH Marquett, R. M., Thompson, L. W., Reiser, R. P., Holland, J. M., O'Hara, R. M., Kesler, S. R., Stepanenko, A., Bilbrey, A., Rengifo, J., Majoros, A., Thompson, D. G. 2013; 17 (7): 830-838


    Objective: The primary objective of this study was to examine a variety of potential predictors of response to Cognitive Behavioral Therapy (CBT) in depressed older adults. Method: Sixty older adults with a clinical diagnosis of major or minor depression or dysthymic disorder received 12 individual sessions of CBT over a three- to four-month-period. The BDI-II was administered pre- and post-intervention to assess change in the level of depression. A cutoff score of 13 or less at post was used to determine positive treatment response. A variety of measures (obtained at baseline) were evaluated using hierarchical regression techniques to predict improvement following treatment. Results: Individuals who showed greater improvement were: (a) more open to new experiences; (b) less negatively affected by past stressors; (c) less inclined to have an external locus of control but more likely to cite others as responsible for negative stress in their lives; and (d) were more likely to seek emotional support when symptomatic. Lower education level and reported use of active coping strategies at baseline were associated with less improvement. Other variables (e.g., age, overall physical health, and cognitive status) were not associated with treatment response. Use of logistic regression to predict responders vs. nonresponders yielded a similar pattern. Conclusion: These findings agree with prior research confirming the effectiveness of a brief CBT intervention for older depressed persons and suggest further exploration of several psychosocial factors that may contribute to a stronger response to CBT.

    View details for DOI 10.1080/13607863.2013.791661

    View details for Web of Science ID 000323476600008

    View details for PubMedID 23631698

  • Comparing connectivity pattern and small-world organization between structural correlation and resting-state networks in healthy adults. NeuroImage Hosseini, S. M., Kesler, S. R. 2013; 78: 402-414


    In recent years, coordinated variations in brain morphology (e.g. volume, thickness, surface area) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks (SCNs). However, it remains unclear how morphometric correlations relate to functional connectivity between brain regions. Resting-state networks (RSNs), derived from coordinated variations in neural activity at rest, have been shown to reflect connectivity between functionally related regions as well as, to some extent, anatomical connectivity between brain regions. Therefore, it is intriguing to investigate similarities between SCN and RSN to help identify how morphometric correlations relate to connections defined by resting-state connectivity. We investigated the similarities in connectivity patterns and small-world organization between SCN, derived from correlations of regional gray matter volume across individuals, and RSN in 36 healthy individuals. The results showed a significant similarity between SCN and RSN (60% for positive connections and 40% for negative connections) that might be explained by shared experience-related functional connectivity underlying both SCN and RSN. Conversely, the small-world parameters of the networks were significantly different, suggesting that SCN topological parameters cannot be regarded as a substitute for topological organization in resting-state networks. While our data suggest that using structural correlation networks can be useful in understanding alterations in structural associations in various brain disorders, it should be noted that a portion of the observed alterations might be explained by factors other than those reflecting resting-state connectivity.

    View details for DOI 10.1016/j.neuroimage.2013.04.032

    View details for PubMedID 23603348

  • Cognitive Training for Improving Executive Function in Chemotherapy-Treated Breast Cancer Survivors CLINICAL BREAST CANCER Kesler, S., Hosseini, S. M., Heckler, C., Janelsins, M., Palesh, O., Mustian, K., Morrow, G. 2013; 13 (4): 299-306


    BACKGROUND: A majority of breast cancer (BC) survivors, particularly those treated with chemotherapy, experience long-term cognitive deficits that significantly reduce quality of life. Among the cognitive domains most commonly affected include executive functions (EF), such as working memory, cognitive flexibility, multitasking, planning, and attention. Previous studies in other populations have shown that cognitive training, a behavioral method for treating cognitive deficits, can result in significant improvements in a number of cognitive skills, including EF. MATERIALS AND METHODS: In this study, we conducted a randomized controlled trial to investigate the feasibility and preliminary effectiveness of a novel, online EF training program in long-term BC survivors. A total of 41 BC survivors (21 active, 20 wait list) completed the 48 session training program over 12 weeks. The participants were, on average, 6 years after therapy. Results: Cognitive training led to significant improvements in cognitive flexibility, verbal fluency and processing speed, with marginally significant downstream improvements in verbal memory as assessed via standardized measures. Self-ratings of EF skills, including planning, organizing, and task monitoring, also were improved in the active group compared with the wait list group. CONCLUSIONS: Our findings suggest that EF skills may be improved even in long-term survivors by using a computerized, home-based intervention program. These improvements may potentially include subjective EF skills, which suggest a transfer of the training program to real-world behaviors.

    View details for DOI 10.1016/j.clbc.2013.02.004

    View details for Web of Science ID 000321239600011

    View details for PubMedID 23647804

  • Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kesler, S. R., Wefel, J. S., Hosseini, S. M., Cheung, M., Watson, C. L., Hoeft, F. 2013; 110 (28): 11600-11605


    Breast cancer (BC) chemotherapy is associated with cognitive changes including persistent deficits in some individuals. We tested the accuracy of default mode network (DMN) resting state functional connectivity patterns in discriminating chemotherapy treated (C+) from non-chemotherapy (C-) treated BC survivors and healthy controls (HC). We also examined the relationship between DMN connectivity patterns and cognitive function. Multivariate pattern analysis was used to classify 30 C+, 27 C-, and 24 HC, which showed significant accuracy for discriminating C+ from C- (91.23%, P < 0.0001) and C+ from HC (90.74%, P < 0.0001). The C- group did not differ significantly from HC (47.06%, P = 0.60). Lower subjective memory function was correlated (P < 0.002) with greater hyperplane distance (distance from the linear decision function that optimally separates the groups). Disrupted DMN connectivity may help explain long-term cognitive difficulties following BC chemotherapy.

    View details for DOI 10.1073/pnas.1214551110

    View details for Web of Science ID 000321827000085

    View details for PubMedID 23798392

  • Influence of Choice of Null Network on Small-World Parameters of Structural Correlation Networks PLOS ONE Hosseini, S. M., Kesler, S. R. 2013; 8 (6)


    In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.

    View details for DOI 10.1371/journal.pone.0067354

    View details for Web of Science ID 000321148400063

    View details for PubMedID 23840672

  • Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties NEUROIMAGE Hosseini, S. M., Black, J. M., Soriano, T., Bugescu, N., Martinez, R., Raman, M. M., Kesler, S. R., Hoeft, F. 2013; 71: 260-274


    Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graph-theoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH-) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome.

    View details for DOI 10.1016/j.neuroimage.2013.01.013

    View details for Web of Science ID 000316154400026

    View details for PubMedID 23333415

  • Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors BRAIN BEHAVIOR AND IMMUNITY Kesler, S., Janelsins, M., Koovakkattu, D., Palesh, O., Mustian, K., Morrow, G., Dhabhar, F. S. 2013; 30: S109-S116


    Many survivors of breast cancer show significant cognitive impairments, including memory deficits. Inflammation induced by chemotherapy may contribute to hippocampal changes that underlie these deficits. In this cross-sectional study, we measured bilateral hippocampal volumes from high-resolution magnetic resonance images in 42 chemotherapy-treated breast cancer survivors and 35 healthy female controls. Patients with breast cancer were, on average, 4.8 ± 3.4 years off-therapy. In a subset of these participants (20 breast cancer, 23 controls), we quantified serum cytokine levels. Left hippocampal volumes and memory performance were significantly reduced and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF?) concentrations were significantly elevated in the breast cancer group compared to controls. In the breast cancer group, lower left hippocampal volume was associated with higher levels of TNF? and lower levels of IL-6 with a significant interaction between these two cytokines suggesting a potential modulatory effect of IL-6 on TNF?. Verbal memory performance was associated with cytokine levels and left hippocampal volume in both groups. These findings provide evidence of altered hippocampal volume and verbal memory difficulties following breast cancer chemotherapy that may be mediated by TNF? and IL-6.

    View details for DOI 10.1016/j.bbi.2012.05.017

    View details for Web of Science ID 000316510800013

    View details for PubMedID 22698992

  • Cognitive outcomes in pediatric heart transplant recipients bridged to transplantation with ventricular assist devices JOURNAL OF HEART AND LUNG TRANSPLANTATION Stein, M. L., Bruno, J. L., Konopacki, K. L., Kesler, S., Reinhartz, O., Rosenthal, D. 2013; 32 (2): 212-220


    Ventricular assist devices (VADs) have been associated with high rates of neurologic injury in pediatric patients during the period of support, but the delayed consequences of this type of injury have not been described in the literature.In this study we assess cognitive outcomes with indices of general intellectual functioning, including working memory, processing speed, perceptual reasoning and verbal comprehension, for pediatric heart transplant recipients who required VAD support as a bridge to transplant (n = 9). We present an aggregate of these VAD patients combined with heart transplant recipients who did not require mechanical circulatory support (n = 11), and compare the performance of all transplant patients (n = 20) to typically developing, healthy comparators (n = 12). We also present a post hoc analysis of those transplant recipients with significant medical morbidity in the first year of life, referred to as the "high-risk" transplant group (n = 5), and compare them with the "low-risk" transplant group (n = 15) and the typically developing comparators (n = 12).The mean performance of the VAD patients was in the average range for each of the examined indices of cognitive functioning. A total of 11% of the VAD patients performed in the impaired range and 78% performed in the average range, with 11% in the superior range on measures of general intellectual functioning. The typically developing participants performed significantly better than the aggregated transplant recipients on all indices except verbal comprehension. Lower cognitive performance in the combined transplant group appears to be associated with medical morbidity in the first year of life.Despite significant neurologic risk factors, this cohort of pediatric patients who were bridged to transplant with VAD demonstrated resiliency in terms of cognitive outcomes. In this heterogeneous population, it is likely that multiple factors contributed to the cognitive outcomes. As VAD use becomes more common in pediatric patients, a prospective evaluation of cognitive outcomes is warranted.

    View details for DOI 10.1016/j.healun.2012.11.006

    View details for Web of Science ID 000314445800006

    View details for PubMedID 23352393

  • Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors NEUROBIOLOGY OF DISEASE Bruno, J., Hosseini, S. M., Kesler, S. 2012; 48 (3): 329-338


    Many women with breast cancer, especially those treated with chemotherapy, experience cognitive decline due in part to neurotoxic brain injury. Recent neuroimaging studies suggest widespread brain structural abnormalities pointing to disruption of large-scale brain networks. We applied resting state functional magnetic resonance imaging and graph theoretical analysis to examine the connectome in breast cancer survivors treated with chemotherapy relative to healthy comparison women. Compared to healthy females, the breast cancer group displayed altered global brain network organization characterized by significantly decreased global clustering as well as disrupted regional network characteristics in frontal, striatal and temporal areas. Breast cancer survivors also showed significantly increased self-report of executive function and memory difficulties compared to healthy females. These results suggest that topological organization of both global and regional brain network properties may be disrupted following breast cancer and chemotherapy. This pattern of altered network organization is believed to result in reduced efficiency of parallel information transfer. This is the first report of alterations in large-scale functional brain networks in this population and contributes novel information regarding the neurobiologic mechanisms underlying breast cancer-related cognitive impairment.

    View details for DOI 10.1016/j.nbd.2012.07.009

    View details for Web of Science ID 000309694000007

    View details for PubMedID 22820143

  • Impact of paroxetine on sleep problems in 426 cancer patients receiving chemotherapy: A trial from the University of Rochester Cancer Center Community Clinical Oncology Program SLEEP MEDICINE Palesh, O. G., Mustian, K. M., Peppone, L. J., Janelsins, M., Sprod, L. K., Kesler, S., Innominato, P. F., Roth, T., Manber, R., Heckler, C., Fiscella, K., Morrow, G. R. 2012; 13 (9): 1184-1190


    Sleep problems are a frequent distressing symptom in cancer patients, yet little is known about their treatment. Sleep problems and depression frequently co-occur, leading healthcare professionals to treat depression with the expectation that sleep problems will also improve. The purpose of this study was to compare the effect of paroxetine to placebo on sleep problems via a secondary data analysis of a RCT designed to compare the effects of paroxetine to placebo on fatigue in cancer patients undergoing chemotherapy. A previously published report found a significant effect of paroxetine on depression in this cohort.A total of 426 patients were randomized following Cycle 2 of chemotherapy to receive either 20mg of paroxetine or placebo. Sleep problems were assessed using questions from the Hamilton Depression Inventory three times during chemotherapy.A total of 217 patients received paroxetine and 209 received placebo. Significantly fewer patients taking paroxetine reported sleep problems compared to patients on placebo (Paroxetine 79% versus Placebo 88%; p<0.05). These differences remained significant even after controlling for baseline sleep problems and depression (p<0.05).Paroxetine had a significant benefit on sleep problems in both depressed and non-depressed cancer patients. However, rates of sleep problems remained high even among those effectively treated for depression with paroxetine. There is a need to develop and deliver sleep-specific interventions to effectively treat sleep-related side effects of cancer treatments. These findings suggest that sleep problems and depression are prevalent and co-morbid. Cancer progression, its response to treatment, and overall patient survival are intricately linked to host factors, such as inflammatory response and circadian rhythms, including sleep/wake cycles. Sleep problems and depression are modifiable host factors that can influence inflammation and impact cancer progression and quality of life. Future research should focus on discovering the pathogenesis of sleep dysregulation and depression in cancer so that better treatment approaches can be developed to ameliorate these symptoms.

    View details for DOI 10.1016/j.sleep.2012.06.001

    View details for Web of Science ID 000311477200012

    View details for PubMedID 22858235

  • GAT: A Graph-Theoretical Analysis Toolbox for Analyzing Between-Group Differences in Large-Scale Structural and Functional Brain Networks PLOS ONE Hosseini, S. M., Hoeft, F., Kesler, S. R. 2012; 7 (7)


    In recent years, graph theoretical analyses of neuroimaging data have increased our understanding of the organization of large-scale structural and functional brain networks. However, tools for pipeline application of graph theory for analyzing topology of brain networks is still lacking. In this report, we describe the development of a graph-analysis toolbox (GAT) that facilitates analysis and comparison of structural and functional network brain networks. GAT provides a graphical user interface (GUI) that facilitates construction and analysis of brain networks, comparison of regional and global topological properties between networks, analysis of network hub and modules, and analysis of resilience of the networks to random failure and targeted attacks. Area under a curve (AUC) and functional data analyses (FDA), in conjunction with permutation testing, is employed for testing the differences in network topologies; analyses that are less sensitive to the thresholding process. We demonstrated the capabilities of GAT by investigating the differences in the organization of regional gray-matter correlation networks in survivors of acute lymphoblastic leukemia (ALL) and healthy matched Controls (CON). The results revealed an alteration in small-world characteristics of the brain networks in the ALL survivors; an observation that confirm our hypothesis suggesting widespread neurobiological injury in ALL survivors. Along with demonstration of the capabilities of the GAT, this is the first report of altered large-scale structural brain networks in ALL survivors.

    View details for DOI 10.1371/journal.pone.0040709

    View details for Web of Science ID 000306406700047

    View details for PubMedID 22808240

  • Altered small-world properties of gray matter networks in breast cancer BMC NEUROLOGY Hosseini, S. M., Koovakkattu, D., Kesler, S. R. 2012; 12


    Breast cancer survivors, particularly those treated with chemotherapy, are at significantly increased risk for long-term cognitive and neurobiologic impairments. These deficits tend to involve skills that are subserved by distributed brain networks. Additionally, neuroimaging studies have shown a diffuse pattern of brain structure changes in chemotherapy-treated breast cancer survivors that might impact large-scale brain networks.We therefore applied graph theoretical analysis to compare the gray matter structural networks of female breast cancer survivors with a history of chemotherapy treatment and healthy age and education matched female controls.Results revealed reduced clustering coefficient and small-world index in the brain network of the breast cancer patients across a range of network densities. In addition, the network of the breast cancer group had less highly interactive nodes and reduced degree/centrality in the frontotemporal regions compared to controls, which may help explain the common impairments of memory and executive functioning among these patients.These results suggest that breast cancer and chemotherapy may decrease regional connectivity as well as global network organization and integration, reducing efficiency of the network. To our knowledge, this is the first report of altered large-scale brain networks associated with breast cancer and chemotherapy.

    View details for DOI 10.1186/1471-2377-12-28

    View details for Web of Science ID 000306755500001

    View details for PubMedID 22632066

  • Maternal history of reading difficulty is associated with reduced language-related gray matter in beginning readers NEUROIMAGE Black, J. M., Tanaka, H., Stanley, L., Nagamine, M., Zakerani, N., Thurston, A., Kesler, S., Hulme, C., Lyytinen, H., Glover, G. H., Serrone, C., Raman, M. M., Reiss, A. L., Hoeft, F. 2012; 59 (3): 3021-3032


    Family history and poor preliteracy skills (referred to here as familial and behavioral risk, respectively) are critical predictors of developmental dyslexia. This study systematically investigated the independent contribution of familial and behavioral risks on brain structures, which had not been explored in past studies. We also examined the differential effects of maternal versus paternal history on brain morphometry, and familial risk dimensionally versus categorically, which were also novel aspects of the study. We assessed 51 children (5 to 6 years of age) with varying degrees of familial and behavioral risks for developmental dyslexia and examined associations with brain morphometry. We found that greater maternal history of reading disability was associated with smaller bilateral prefrontal and parieto-temporal gray, but not white matter volumes. Regressing out behavioral risk, socioeconomic status, and maternal education and other confounds did not change the results. No such relationship was observed for paternal reading history and behavioral risk. Results of cortical surface area and thickness further showed that there was a significant negative relationship between cortical surface area (but not thickness) and greater severity of maternal history, in particular within the left inferior parietal lobule, suggesting prenatal influence of maternal history on children's brain morphometry. The results suggested greater maternal, possibly prenatal, influence on language-related brain structures. These results help to guide future neuroimaging research focusing on environmental and genetic influences and provide new information that may help predict which child will develop dyslexia in the future.

    View details for DOI 10.1016/j.neuroimage.2011.10.024

    View details for Web of Science ID 000299494000100

    View details for PubMedID 22023744

  • Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer. Nature and science of sleep Palesh, O., Peppone, L., Innominato, P. F., Janelsins, M., Jeong, M., Sprod, L., Savard, J., Rotatori, M., Kesler, S., Telli, M., Mustian, K. 2012; 4: 151-162


    Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients receiving chemotherapy. Optimal management of sleep problems in patients with cancer receiving treatment may improve not only the well-being of patients, but also their prognosis given the emerging experimental and clinical evidence suggesting that sleep disruption might adversely impact treatment and recovery from cancer.

    View details for PubMedID 23486503

  • The Brain Basis of the Phonological Deficit in Dyslexia Is Independent of IQ PSYCHOLOGICAL SCIENCE Tanaka, H., Black, J. M., Hulme, C., Stanley, L. M., Kesler, S. R., Whitfield-Gabrieli, S., Reiss, A. L., Gabrieli, J. D., Hoeft, F. 2011; 22 (11): 1442-1451


    Although the role of IQ in developmental dyslexia remains ambiguous, the dominant clinical and research approaches rely on a definition of dyslexia that requires reading skill to be significantly below the level expected given an individual's IQ. In the study reported here, we used functional MRI (fMRI) to examine whether differences in brain activation during phonological processing that are characteristic of dyslexia were similar or dissimilar in children with poor reading ability who had high IQ scores (discrepant readers) and in children with poor reading ability who had low IQ scores (nondiscrepant readers). In two independent samples including a total of 131 children, using univariate and multivariate pattern analyses, we found that discrepant and nondiscrepant poor readers exhibited similar patterns of reduced activation in brain areas such as left parietotemporal and occipitotemporal regions. These results converge with behavioral evidence indicating that, regardless of IQ, poor readers have similar kinds of reading difficulties in relation to phonological processing.

    View details for DOI 10.1177/0956797611419521

    View details for Web of Science ID 000300826400015

    View details for PubMedID 22006060

  • Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer ARCHIVES OF NEUROLOGY Kesler, S. R., Kent, J. S., O'Hara, R. 2011; 68 (11): 1447-1453


    To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables.Observational study.University-based research facility.Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables.Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group.These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

    View details for Web of Science ID 000297014900013

    View details for PubMedID 22084128

  • The Feasibility of Detecting Neuropsychologic and Neuroanatomic Effects of Type 1 Diabetes in Young Children DIABETES CARE Aye, T., Reiss, A. L., Kesler, S., Hoang, S., Drobny, J., Park, Y., Schleifer, K., Baumgartner, H., Wilson, D. M., Buckingham, B. A. 2011; 34 (7): 1458-1462


    To determine if frequent exposures to hypoglycemia and hyperglycemia during early childhood lead to neurocognitive deficits and changes in brain anatomy.In this feasibility, cross-sectional study, young children, aged 3 to 10 years, with type 1 diabetes and age- and sex-matched healthy control (HC) subjects completed neuropsychologic (NP) testing and magnetic resonance imaging (MRI) scans of the brain.NP testing and MRI scanning was successfully completed in 98% of the type 1 diabetic and 93% of the HC children. A significant negative relationship between HbA1c and Wechsler Intelligence Scale for Children (WISC) verbal comprehension was observed. WISC index scores were significantly reduced in type 1 diabetic subjects who had experienced seizures. White matter volume did not show the expected increase with age in children with type 1 diabetes compared with HC children (diagnosis by age interaction, P=0.005). A similar trend was detected for hippocampal volume. Children with type 1 diabetes who had experienced seizures showed significantly reduced gray matter and white matter volumes relative to children with type 1 diabetes who had not experienced seizures.It is feasible to perform MRI and NP testing in young children with type 1 diabetes. Further, early signs of neuroanatomic variation may be present in this population. Larger cross-sectional and longitudinal studies of neurocognitive function and neuroanatomy are needed to define the effect of type 1 diabetes on the developing brain.

    View details for DOI 10.2337/dc10-2164

    View details for Web of Science ID 000293261200003

    View details for PubMedID 21562318

  • Consequence of Preterm Birth in Early Adolescence: The Role of Language on Auditory Short-term Memory JOURNAL OF CHILD NEUROLOGY Fraello, D., Maller-Kesselman, J., Vohr, B., Katz, K. H., Kesler, S., Schneider, K., Reiss, A., Ment, L., Spann, M. N. 2011; 26 (6): 738-742


    This study tested the hypothesis that preterm early adolescents' short-term memory is compromised when presented with increasingly complex verbal information and that associated neuroanatomical volumes would differ between preterm and term groups. Forty-nine preterm and 20 term subjects were evaluated at age 12 years with neuropsychological measures and magnetic resonance imaging (MRI). There were no differences between groups in simple short-term and working memory. Preterm subjects performed lower on learning and short-term memory tests that included increased verbal complexity. They had reduced right parietal, left temporal, and right temporal white matter volumes and greater bilateral frontal gray and right frontal white matter volumes. There was a positive association between complex working memory and the left hippocampus and frontal white matter in term subjects. While not correlated, memory scores and volumes of cortical regions known to subserve language and memory were reduced in preterm subjects. This study provides evidence of possible mechanisms for learning problems in former preterm infants.

    View details for DOI 10.1177/0883073810391904

    View details for Web of Science ID 000290961000012

    View details for PubMedID 21471553

  • A pilot study of an online cognitive rehabilitation program for executive function skills in children with cancer-related brain injury BRAIN INJURY Kesler, S. R., Lacayo, N. J., Jo, B. 2011; 25 (1): 101-112


    Children with a history of cancer are at increased risk for cognitive impairments, particularly in executive and memory domains. Traditional, in-person cognitive rehabilitation strategies may be unavailable and/or impractical for many of these children given difficulties related to resources and health status. The feasibility and efficacy of implementing a computerized, home-based cognitive rehabilitation curriculum designed to improve executive function skills was examined in these children.A one-arm open trial pilot study of an original executive function cognitive rehabilitation curriculum was conducted with 23 paediatric cancer survivors aged 7-19.Compliance with the cognitive rehabilitation program was 83%, similar to that of many traditional programs. Following the cognitive intervention, participants showed significantly increased processing speed, cognitive flexibility, verbal and visual declarative memory scores as well as significantly increased pre-frontal cortex activation compared to baseline.These results suggest that a program of computerized cognitive exercises can be successfully implemented at home in young children with cancer. These exercises may be effective for improving executive and memory skills in this group, with concurrent changes in neurobiologic status.

    View details for DOI 10.3109/02699052.2010.536194

    View details for Web of Science ID 000288101700011

    View details for PubMedID 21142826

  • Changes in frontal-parietal activation and math skills performance following adaptive number sense training: Preliminary results from a pilot study NEUROPSYCHOLOGICAL REHABILITATION Kesler, S. R., Sheau, K., Koovakkattu, D., Reiss, A. L. 2011; 21 (4): 433-454


    Number sense is believed to be critical for math development. It is putatively an implicitly learned skill and may therefore have limitations in terms of being explicitly trained, particularly in individuals with altered neurodevelopment. A case series study was conducted using an adaptive, computerised programme that focused on number sense and general problem-solving skills. The study was designed to investigate training effects on performance as well as brain function in a group of children with Turner syndrome who are at risk for math difficulties and altered development of math-related brain networks. Standardised measurements of math and math-related cognitive skills as well as functional magnetic resonance imaging (fMRI) were used to assess behavioural and neurobiological outcomes following training. Participants demonstrated significantly increased basic math skills, including number sense, and calculation as well as processing speed, cognitive flexibility and visual-spatial processing skills. With the exception of calculation, increased scores also were clinically significant (i.e., recovered) based on reliable change analysis. Participants additionally demonstrated significantly increased bilateral parietal lobe activation and decreased frontal-striatal and mesial temporal activation following the training programme. These findings show proof of concept for an accessible training approach that may be potentially associated with improved number sense, math and related skills, as well as functional changes in math-related neural systems, even among individuals at risk for altered brain development.

    View details for DOI 10.1080/09602011.2011.578446

    View details for Web of Science ID 000299788700001

    View details for PubMedID 21714745

  • Cognitive reserve and brain volumes in pediatric acute lymphoblastic leukemia BRAIN IMAGING AND BEHAVIOR Kesler, S. R., Tanaka, H., Koovakkattu, D. 2010; 4 (3-4): 256-269


    Acute lymphoblastic leukemia (ALL) is associated with long-term, progressive cognitive deficits and white matter injury. We measured global and regional white and gray matter as well as cognitive function and examined relationships between these variables and cognitive reserve, as indicated by maternal education level, in 28 young survivors of ALL and 31 healthy controls. Results indicated significantly reduced white matter volumes and cognitive testing scores in the ALL group compared to controls. Maternal education was inversely related to both global and regional white matter and directly related to gray matter in ALL and was directly related to both gray and white matter in controls, consistent with the cognitive reserve hypothesis. Cognitive performance was associated with different brain regions in ALL compared to controls. Maternal education was significantly positively correlated with working and verbal memory in ALL as well as processing speed and verbal memory in controls, improving models of cognitive outcome over medical and/or demographic predictors. Our findings suggest that cognitive reserve may be an important factor in brain injury and cognitive outcome in ALL. Additionally, children with ALL may experience some neural reorganization related to cognitive outcome.

    View details for DOI 10.1007/s11682-010-9104-1

    View details for Web of Science ID 000282508600006

    View details for PubMedID 20814845

  • Regional Brain Activation during Verbal Declarative Memory in Metastatic Breast Cancer CLINICAL CANCER RESEARCH Kesler, S. R., Bennett, F. C., Mahaffey, M. L., Spiegel, D. 2009; 15 (21): 6665-6673


    To determine the neurofunctional basis of verbal memory dysfunction in women with metastatic breast cancer. This objective was based on previous research suggesting memory and other cognitive deficits in this population. We attempted to determine if verbal memory impairments were related to the most commonly studied disease parameters including adjuvant chemotherapy and chronic stress-related disruption of limbic system structures.We used functional magnetic resonance imaging to test our hypothesis that women with breast cancer would show significantly lower brain activation during verbal declarative memory tasks compared with age and education-matched healthy female controls. We also assessed several stress-related variables including diurnal cortisol levels to test our hypothesis that women with breast cancer would show higher stress and this would contribute to brain activation deficits during memory tasks.Women with breast cancer had significantly lower prefrontal cortex activation during the memory encoding condition compared with controls. However, the breast cancer group showed significantly greater activation than controls during the recall condition in multiple, diffuse brain regions. There were no significant differences between the groups in stress-related variables. Women who were treated with cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy showed lower prefrontal cortex activation during memory encoding.These results suggest that women with metastatic breast cancer may be at risk for verbal memory impairments as a result of altered functional brain activation profiles. These findings may be associated with chemotherapy type and/or other aspects of the breast cancer disease process.

    View details for DOI 10.1158/1078-0432.CCR-09-1227

    View details for Web of Science ID 000271300200024

    View details for PubMedID 19843664

  • The impact of spermine synthase (SMS) mutations on brain morphology NEUROGENETICS Kesler, S. R., Schwartz, C., Stevenson, R. E., Reiss, A. L. 2009; 10 (4): 299-305


    Snyder-Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome. We obtained cerebral, cerebellum, hippocampus, and red nucleus volumes from two males with SRS and 24 age- and gender-matched typically developing controls using volumetric neuroimaging analyses. Total brain volume was enlarged in males with SRS while cerebellum, hippocampus, and red nucleus volumes tended to be reduced compared to controls. Mutations of the X chromosome may modulate the risk for mental retardation through altered early neurodevelopment, disruption in receptor function, and ongoing neural organization and plasticity. Disruption of SMS function may negatively affect regional brain volumes that subserve cognitive and motor abilities. This research provides valuable insight into the effects of polyamine function on brain development.

    View details for DOI 10.1007/s10048-009-0184-2

    View details for Web of Science ID 000270386000003

    View details for PubMedID 19277733

  • Cholinergic Dysfunction in Fragile X Syndrome and Potential Intervention: A Preliminary H-1 MRS Study AMERICAN JOURNAL OF MEDICAL GENETICS PART A Kesler, S. R., Lightbody, A. A., Reiss, A. L. 2009; 149A (3): 403-407


    Males with fragile X syndrome (FRAX) are at risk for significant cognitive and behavioral deficits, particularly those involving executive prefrontal systems. Disruption of the cholinergic system secondary to fragile X mental retardation protein deficiency may contribute to the cognitive-behavioral impairments associated with fragile X. We measured choline in the dorsolateral prefrontal cortex of nine males with FRAX and 9 age-matched typically developing controls using (1)H magnetic resonance spectroscopy. Right choline/creatine was significantly reduced in the fragile X group compared to controls. In controls, both left and right choline was significantly positively correlated with intelligence and age was significantly negatively correlated with left choline. There were no correlations in the fragile X group. Subjects with FRAX participating in a pilot open-label trial of donepezil, an acetylcholinesterase inhibitor, demonstrated significantly improved cognitive-behavioral function. Studies utilizing biochemical neuroimaging techniques such as these have the potential to significantly impact the design of treatment strategies for FRAX and other genetic disorders by helping identify neurochemical targets for intervention as well as serving as metrics for treatment efficacy.

    View details for DOI 10.1002/ajmg.a.32697

    View details for Web of Science ID 000264142300018

    View details for PubMedID 19215057

  • Alterations in functional connectivity for language in prematurely born adolescents BRAIN Schafer, R. J., Lacadie, C., Vohr, B., Kesler, S. R., Katz, K. H., Schneider, K. C., Pugh, K. R., Makuch, R. W., Reiss, A. L., Constable, R. T., Ment, L. R. 2009; 132: 661-670


    Recent data suggest recovery of language systems but persistent structural abnormalities in the prematurely born. We tested the hypothesis that subjects who were born prematurely develop alternative networks for processing language. Subjects who were born prematurely (n = 22; 600-1250 g birth weight), without neonatal brain injury on neonatal cranial ultrasound, and 26 term control subjects were examined with a functional magnetic resonance imaging (fMRI) semantic association task, the Wechsler Intelligence Scale for Children-III (WISC-III) and the Clinical Evaluation of Language Fundamentals (CELF). In-magnet task accuracy and response times were calculated, and fMRI data were evaluated for the effect of group on blood oxygen level dependent (BOLD) activation, the correlation between task accuracy and activation and the functional connectivity between regions activating to task. Although there were differences in verbal IQ and CELF scores between the preterm (PT) and term control groups, there were no significant differences for either accuracy or response time for the in-magnet task. Both groups activated classic semantic processing areas including the left superior and middle temporal gyri and inferior frontal gyrus, and there was no significant difference in activation patterns between groups. Clear differences between the groups were observed in the correlation between task accuracy and activation to task at P < 0.01, corrected for multiple comparisons. Left inferior frontal gyrus correlated with accuracy only for term controls and left sensory motor areas correlated with accuracy only for PT subjects. Left middle temporal gyri correlated with task accuracy for both groups. Connectivity analyses at P < 0.001 revealed the importance of a circuit between left middle temporal gyri and inferior frontal gyrus for both groups. In addition, the PT subjects evidenced greater connectivity between traditional language areas and sensory motor areas but significantly fewer correlated areas within the frontal lobes when compared to term controls. We conclude that at 12 years of age, children born prematurely and children born at term had no difference in performance on a simple lexical semantic processing task and activated similar areas. Connectivity analyses, however, suggested that PT subjects rely upon different neural pathways for lexical semantic processing when compared to term controls. Plasticity in network connections may provide the substrate for improving language skills in the prematurely born.

    View details for DOI 10.1093/brain/awn353

    View details for Web of Science ID 000264889000011

    View details for PubMedID 19158105

  • Longitudinal Brain Volume Changes in Preterm and Term Control Subjects During Late Childhood and Adolescence PEDIATRICS Ment, L. R., Kesler, S., Vohr, B., Katz, K. H., Baumgartner, H., Schneider, K. C., Delancy, S., Silbereis, J., Duncan, C. C., Constable, R. T., Makuch, R. W., Reiss, A. L. 2009; 123 (2): 503-511


    Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain.We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study.Total brain volumes increased 2% to 3% between the ages of 8 and 12 years for both preterm and term children. These changes involved reductions in cerebral gray matter while white matter increased. Between 8 and 12 years of age, preterm subjects experienced a 2% decrease in left cerebral gray matter compared with a 10% reduction in left cerebral gray for term controls. For right cerebral gray matter, preterm children experienced a 3% decrease in volume between years 8 and 12, compared with 9% for term controls (group-by-time). In contrast, preterm subjects had a 10% increase in cerebral white matter volumes bilaterally between ages 8 and 12 years, compared with >26% increases for both hemispheres for term controls. Significant differences in regional volume changes between study groups were found in bilateral temporal gray and in parietal white matter.Preterm birth continues to perturb the trajectory of cerebral development during late childhood and early adolescence with preterm children, showing both lower gray matter reduction and less white matter gain over time compared with term control subjects.

    View details for DOI 10.1542/peds.2008-0025

    View details for Web of Science ID 000262678700012

    View details for PubMedID 19171615



    Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this report, we review previous and current research related to the cognitive profile of TS. We also discuss how cognitive impairments in this syndrome may reflect integrative rather than modular deficits. For example, the less commonly reported areas of verbal difficulty in TS and certain visual-spatial deficits seem significantly influenced by impairments in executive function and spatially loaded stimuli. We provide a summary of cognitive testing measures used in the assessment of visual-spatial and executive skills, which includes test domain descriptions as well as a comprehensive examination of social cognitive function in TS. This review concludes with a discussion of ecological interpretations regarding the meaning of cognitive deficits in TS at the individual level.

    View details for DOI 10.1002/ddrr.79

    View details for Web of Science ID 000273207500002

    View details for PubMedID 20014362

  • Brain volume reductions within multiple cognitive systems in male preterm children at age twelve JOURNAL OF PEDIATRICS Kesler, S. R., Reiss, A. L., Vohr, B., Watson, C., Schneider, K. C., Katz, K. H., Maller-Kesselman, J., Silberes, J., Constable, R. T., Makuch, R. W., Ment, L. R. 2008; 152 (4): 513-520


    To more precisely examine regional and subregional microstructural brain changes associated with preterm birth.We obtained brain volumes from 29 preterm children, age 12 years, with no ultrasound scanning evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in the newborn period, and 22 age- and sex-matched term control subjects.Preterm male subjects demonstrated significantly lower white matter volumes in bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex, superior and inferior longitudinal fasciculi compared with term male subjects. Gray matter volumes in prefrontal cortex, basal ganglia, and temporal lobe also were significantly reduced in preterm male subjects. Brain volumes of preterm female subjects were not significantly different from those of term female control subjects. Voxel-based morphometry results were not correlated with perinatal variables or cognitive outcome. Higher maternal education was associated with higher cognitive performance in preterm male subjects.Preterm male children continue to demonstrate abnormal neurodevelopment at 12 years of age. However, brain morphology in preterm female children may no longer differ from that of term female children. The neurodevelopmental abnormalities we detected in preterm male subjects appear to be relatively diffuse, involving multiple neural systems. The relationship between aberrant neurodevelopment and perinatal variables may be mediated by genetic factors, environmental factors, or both reflected in maternal education level.

    View details for DOI 10.1016/j.jpeds.2007.08.009

    View details for Web of Science ID 000254543200024

    View details for PubMedID 18346506

  • Gender differences in the mesocorticolimbic system during computer game-play JOURNAL OF PSYCHIATRIC RESEARCH Hoeft, F., Watson, C. L., Kesler, S. R., Bettinger, K. E., Reiss, A. L. 2008; 42 (4): 253-258


    Little is known about the underlying neural processes of playing computer/video games, despite the high prevalence of its gaming behavior, especially in males. In a functional magnetic resonance imaging study contrasting a space-infringement game with a control task, males showed greater activation and functional connectivity compared to females in the mesocorticolimbic system. These findings may be attributable to higher motivational states in males, as well as gender differences in reward prediction, learning reward values and cognitive state during computer video games. These gender differences may help explain why males are more attracted to, and more likely to become "hooked" on video games than females.

    View details for DOI 10.1016/j.jpsychires.2007.11.010

    View details for Web of Science ID 000254137300001

    View details for PubMedID 18194807

  • Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: An investigation of group and gender effects PEDIATRICS Constable, R. T., Ment, L. R., Vohr, B. R., Kesler, S. R., Fulbright, R. K., Lacadie, C., Delancy, S., Katz, K. H., Schneider, K. C., Schafer, R. J., Makuch, R. W., Reiss, A. R. 2008; 121 (2): 306-316


    The goal was to use diffusion tensor imaging to test the hypothesis that prematurely born children demonstrate long-term, white matter, microstructural differences, relative to term control subjects.Twenty-nine preterm subjects (birth weight: 600-1250 g) without neonatal brain injury and 22 matched, term, control subjects were evaluated at 12 years of age with MRI studies, including diffusion tensor imaging and volumetric imaging; voxel-based morphometric strategies were used to corroborate regional diffusion tensor imaging results. Subjects also underwent neurodevelopmental assessments.Neurodevelopmental assessments showed significant differences in full-scale, verbal, and performance IQ and Developmental Test of Visual Motor Integration scores between the preterm and term control subjects. Diffusion tensor imaging studies demonstrated widespread decreases in fractional anisotropy (a measure of fiber tract organization) in the preterm children, compared with the control subjects. Regions included both intrahemispheric association fibers subserving language skills, namely, the right inferior frontooccipital fasciculus and anterior portions of the uncinate fasciculi bilaterally, and the deep white matter regions to which they project, as well as the splenium of the corpus callosum. These changes in fractional anisotropy occurred in subjects with significant differences in frontal, temporal, parietal, and deep white matter volumes. Fractional anisotropy values in the left anterior uncinate correlated with verbal IQ, full-scale IQ, and Peabody Picture Vocabulary Test-Revised scores for preterm male subjects. In addition, preterm male subjects were found to have the lowest values for fractional anisotropy in the right anterior uncinate fasciculus, and fractional anisotropy values in that region correlated with both verbal IQ and Peabody Picture Vocabulary Test-Revised scores for the preterm groups; these findings were supported by changes identified with voxel-based morphometric analyses.Compared with term control subjects, prematurely born children with no neonatal ultrasound evidence of white matter injury manifest changes in neural connectivity at 12 years of age.

    View details for DOI 10.1542/peds.2007-0414

    View details for Web of Science ID 000252877600011

    View details for PubMedID 18245422

  • Craniofacioskeletal syndrome: An X-linked dominant disorder with early lethality in males AMERICAN JOURNAL OF MEDICAL GENETICS PART A Stevenson, R. E., Brasington, C. K., Skinner, C., Simensen, R. J., Spence, J. E., Kesler, S., Reiss, A. L., Schwartz, C. E. 2007; 143A (19): 2321-2329


    A syndrome with multisystem manifestations has been observed in three generations of a Caucasian family. The findings in seven females provide a composite clinical picture of microcephaly, short stature, small retroverted ears, full tip of the nose overhanging the columella, short philtrum, thin upper lip, soft tissue excrescences at the angle of the mouth, small mandible, small hands and feet with brachydactyly, finger V clinodactyly, flat feet, an excessive number of fingerprint arches, and mild impairment of cognitive function. Two males were more severely affected and died in the initial months of life. They showed intrauterine growth retardation, broad cranium with wide sutures and fontanelles, cardiac defects, small hands and feet with abnormal digital creases and small nails, and genital abnormalities. The affected males had low serum calcium in the neonatal period. Serum calcium, phosphorous, and parathormone levels in the females were normal. Radiographs showed cortical thickening of the long bones, underdevelopment of the frontal sinuses, narrow pelvis and hypoplasia of the middle phalanx of finger five. MRI of the brain showed slightly reduced brain volumes and an extra gyrus of the superior temporal region. X-inactivation studies showed near complete skewing in two affected females, but were not informative in three others. X-linkage as the mode of inheritance is proposed on the basis of different severity in males/females, complete skewing of X-inactivation in informative females, and a lod score (1.5) suggestive of linkage to markers in Xq26-q27.

    View details for DOI 10.1002/ajmg.a.31928

    View details for Web of Science ID 000249829900013

    View details for PubMedID 17853486

  • Turner syndrome CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA Kesler, S. R. 2007; 16 (3): 709-?


    Turner syndrome is a neurogenetic disorder characterized by partial or complete monosomy-X. It is associated with certain physical and medical features, including estrogen deficiency, short stature, and increased risk for several diseases, with cardiac conditions being among the most serious. The cognitive-behavioral phenotype associated with the syndrome includes strengths in verbal domains with impairments in visuospatial, executive function, and emotion processing. Less is known regarding psychosocial and psychiatric functioning in Turner syndrome, but essential aspects of psychotherapeutic treatment plans are suggested. Future investigations should include continued genetic studies and determination of candidate genes for physical and cognitive features. Multimodal, interdisciplinary studies are essential for identifying optimal, syndrome-specific interventions for improving the lives of individuals who have Turner syndrome.

    View details for DOI 10.1016/j.chc.2007.02.004

    View details for Web of Science ID 000247944400013

    View details for PubMedID 17562588

  • Altered neurodevelopment associated with mutations of RSK2: a morphometric MRI study of Coffin-Lowry syndrome NEUROGENETICS Kesler, S. R., Simensen, R. J., Voeller, K., Abidi, F., Stevenson, R. E., Schwartz, C. E., Reiss, A. L. 2007; 8 (2): 143-147


    Coffin-Lowry syndrome (CLS) is a rare form of X-linked mental retardation caused by mutations of the RSK2 gene, associated with cognitive impairment and skeletal malformations. We conducted the first morphometric study of CLS brain morphology by comparing brain volumes from two CLS families with healthy controls. Individuals with CLS consistently showed markedly reduced total brain volume. Cerebellum and hippocampus volumes were particularly impacted by CLS and may be associated with specific interfamilial RSK2 mutations. We provide preliminary evidence that the magnitude of hippocampus volume deviation from that of controls may predict general cognitive outcome in CLS.

    View details for DOI 10.1007/s10048-007-0080-6

    View details for Web of Science ID 000244692400009

    View details for PubMedID 17318637

  • Selective alterations of white matter associated with visuospatial and sensorimotor dysfunction in Turner syndrome JOURNAL OF NEUROSCIENCE Holzapfel, M., Barnea-Goraly, N., Eckert, M. A., Kesler, S. R., Reiss, A. L. 2006; 26 (26): 7007-7013


    Turner syndrome (TS) is a neurogenetic disorder characterized by impaired spatial, numerical, and motor functioning but relatively spared verbal ability. Results from previous neuroimaging studies suggest that gray matter alterations in parietal and frontal regions may contribute to atypical visuospatial and executive functioning in TS. Recent findings in TS also indicate variations in the shape of parietal gyri and white matter microstructural anomalies of the temporal lobe. Diffusion tensor imaging and structural imaging methods were used to determine whether 10 females with TS and 10 age- and gender-matched control subjects exhibited differences in fractional anisotropy, white matter density, and local brain shape. Relative to controls, females with TS had lower fractional anisotropy (FA) values in the deep white matter of the left parietal-occipital region extending anteriorly along the superior longitudinal fasciculus into the deep white matter of the frontal lobe. In addition, decreased FA values were located bilaterally in the internal capsule extending into the globus pallidus and in the right prefrontal region. Voxel-based morphometry (VBM) analysis showed corresponding white matter density differences in the internal capsules and left centrum semiovale. Tensor-based morphometry analysis indicated that the FA and VBM results were not attributable to differences in the local shape of brain structures. Compared with controls, females with TS had increases in FA values and white matter density in language-related areas of the inferior parietal and temporal lobes. These complementary analyses provide evidence for alterations in white matter pathways that subserve affected and preserved cognitive functions in TS.

    View details for DOI 10.1523/JNEUROSCI.1764-06.2006

    View details for Web of Science ID 000238804400014

    View details for PubMedID 16807330

  • Neurofunctional differences associated with arithmetic processing in turner syndrome CEREBRAL CORTEX Kesler, S. R., Menon, V., Reiss, A. L. 2006; 16 (6): 849-856


    Turner syndrome (TS) is a neurogenetic disorder characterized by the absence of one X chromosome in a phenotypic female. Individuals with TS are at risk for impairments in mathematics. We investigated the neural mechanisms underlying arithmetic processing in TS. Fifteen subjects with TS and 15 age-matched typically developing controls were scanned using functional MRI while they performed easy (two-operand) and difficult (three-operand) versions of an arithmetic processing task. Both groups activated fronto-parietal regions involved in arithmetic processing during the math tasks. Compared with controls, the TS group recruited additional neural resources in frontal and parietal regions during the easier, two-operand math task. During the more difficult three-operand task, individuals with TS demonstrated significantly less activation in frontal, parietal and subcortical regions than controls. However, the TS group's performance on both math tasks was comparable to controls. Individuals with TS demonstrate activation differences in fronto-parietal areas during arithmetic tasks compared with controls. They must recruit additional brain regions during a relatively easy task and demonstrate a potentially inefficient response to increased task difficulty compared with controls.

    View details for DOI 10.1093/cercor/bhj028

    View details for Web of Science ID 000237525900008

    View details for PubMedID 16135780

  • Increased temporal lobe gyrification in preterm children NEUROPSYCHOLOGIA Kesler, S. R., Vohr, B., Schneider, K. C., Katz, K. H., Makuch, R. W., Reiss, A. L., Ment, L. R. 2006; 44 (3): 445-453


    Preterm birth often results in significant learning disability, and previous magnetic resonance imaging (MRI) studies of preterm children have demonstrated reduction in overall cortical tissue with particular vulnerability in the temporal lobe. We measured cortical gyrification in 73 preterm and 33 term control children at 8 years of age and correlated these findings with tests of language ability to determine the associations among preterm birth, neurodevelopment and functional outcome. Preterm children demonstrated significantly increased bilateral temporal lobe gyrification index compared to term controls. Left temporal gyrification index was significantly negatively correlated with left temporal lobe gray matter volume as well as reading recognition scores in the preterm group. Cortical development in the temporal lobe appears to be differentially vulnerable to preterm birth.

    View details for DOI 10.1016/j.neuropsychologia.2005.05.015

    View details for Web of Science ID 000235861600012

    View details for PubMedID 15985272

  • Volumetric analysis of regional cerebral development in preterm children PEDIATRIC NEUROLOGY Kesler, S. R., Ment, L. R., Vohr, B., Pajot, S. K., Schneider, K. C., Katz, K. H., Ebbitt, T. B., Duncan, C. C., Makuch, R. W., Reiss, A. L. 2004; 31 (5): 318-325


    Preterm birth is frequently associated with both neuropathologic and cognitive sequelae. This study examined cortical lobe, subcortical, and lateral ventricle development in association with perinatal variables and cognitive outcome. High-resolution volumetric magnetic resonance imaging scans were acquired and quantified using advanced image processing techniques. Seventy-three preterm and 33 term control children ages 7.3-11.4 years were included in the study. Results indicated disproportionately enlarged parietal and frontal gray matter, occipital horn, and ventricular body, as well as reduced temporal and subcortical gray volumes in preterm children compared with control subjects. Birth weight was negatively correlated with parietal and frontal gray, as well as occipital horn volumes. Intraventricular hemorrhage was associated with reduced subcortical gray matter. Ventricular cerebrospinal fluid was negatively correlated with subcortical gray matter volumes but not with white matter volumes. Maternal education was the strongest predictor of cognitive function in the preterm group. Preterm birth appears to be associated with disorganized cortical development, possibly involving disrupted synaptic pruning and neural migration. Lower birth weight and the presence of intraventricular hemorrhage may increase the risk for neuroanatomic abnormality.

    View details for DOI 10.1016/j.pediatrneurol.2004.06.008

    View details for Web of Science ID 000225313400002

    View details for PubMedID 15519112

  • A volumetric study of parietal lobe subregions in Turner syndrome DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Brown, W. E., Kesler, S. R., Eliez, S., Warsofsky, I. S., Haberecht, M., Reiss, A. L. 2004; 46 (9): 607-609


    Turner syndrome, a genetic disorder that results from the complete or partial absence of an X chromosome in females, has been associated with specific impairment in visuospatial cognition. Previous studies have demonstrated a relationship between parietal lobe abnormalities and visuospatial deficits in Turner syndrome. We used high-resolution magnetic resonance imaging to measure parietal lobe subdivisions in 14 participants with Turner syndrome (mean age 13 years 5 months, SD 5 years) and 14 age-matched controls (mean age 13 years 5 months, SD 4 years 7 months) to localize neuroanatomical variations more closely. Scans were acquired and analyzed for 14 females with Turner syndrome. Analyses of variance were used to investigate differences in regional parietal lobes. Females with Turner syndrome showed a bilateral parietal lobe reduction, specifically in the superior parietal and postcentral gyri. Full-scale IQ scores were significantly positively correlated with postcentral tissue volume in the Turner syndrome group. Structural differences in the parietal lobe are localized specifically to the anterior and superior parietal lobe and might be related to the visuospatial and visuomotor deficits associated with Turner syndrome.

    View details for DOI 10.1017/S0012162204001021

    View details for Web of Science ID 000223720900005

    View details for PubMedID 15344520

  • Sex differences in cerebral volumes of 8-year-olds born preterm JOURNAL OF PEDIATRICS Reiss, A. L., Kesler, S. R., Vohr, B., Duncan, C. C., Katz, K. H., Pajot, S., Schneider, K. C., Makuch, R. W., Ment, L. R. 2004; 145 (2): 242-249


    We investigate sex-associated effects of preterm birth on cerebral gray matter (GM) and white matter (WM) volumes. Preterm children (n=65) and 31 healthy, term control children had usable magnetic resonance imaging (MRI) data acquired at 8 years of age. Both GM and WM volumes were significantly reduced in the preterm group compared with controls. However, only males with preterm birth had significantly reduced WM compared with term males (P=.021), whereas WM volumes were equivalent in the female groups. Lower birth weight was associated with reduced WM in both boys and girls with preterm birth, whereas intraventricular hemorrhage (IVH) was associated with reduced GM in girls only. Positive correlations between GM and cognitive outcome were observed in girls with preterm birth but not boys. We conclude that preterm birth has a significant impact on brain development with increased risk for smaller GM and WM cerebral volumes. Males appear particularly vulnerable to adverse effects of preterm birth on WM development. However, girls with preterm birth show stronger correlations between neuro-anatomical variables and both neonatal risk factors and cognitive outcome, compared with boys. These findings indicate that the sex of the very preterm newborn influences the mechanisms by which the developing brain is affected.

    View details for DOI 10.1016/j.jpeds.2004.04.031

    View details for Web of Science ID 000223406200024

    View details for PubMedID 15289777

  • An experiment of nature: Brain anatomy parallels cognition and behavior in Williams syndrome JOURNAL OF NEUROSCIENCE Reiss, A. L., Eckert, M. A., Rose, F. E., Karchemskiy, A., Kesler, S., Chang, M., Reynolds, M. F., Kwon, H., Galaburda, A. 2004; 24 (21): 5009-5015


    Williams syndrome (WS) is a neurogenetic-neurodevelopmental disorder characterized by a highly variable and enigmatic profile of cognitive and behavioral features. Relative to overall intellect, affected individuals demonstrate disproportionately severe visual-spatial deficits and enhanced emotionality and face processing. In this study, high-resolution magnetic resonance imaging data were collected from 43 individuals with WS and 40 age- and gender-matched healthy controls. Given the distinct cognitive-behavioral dissociations associated with this disorder, we hypothesized that neuroanatomical integrity in WS would be diminished most in regions comprising the visual-spatial system and most "preserved" or even augmented in regions involved in emotion and face processing. Both volumetric analysis and voxel-based morphometry were used to provide convergent approaches for detecting the hypothesized WS neuroanatomical profile. After adjusting for overall brain volume, participants with WS showed reduced thalamic and occipital lobe gray matter volumes and reduced gray matter density in subcortical and cortical regions comprising the human visual-spatial system compared with controls. The WS group also showed disproportionate increases in volume and gray matter density in several areas known to participate in emotion and face processing, including the amygdala, orbital and medial prefrontal cortices, anterior cingulate, insular cortex, and superior temporal gyrus. These findings point to specific neuroanatomical correlates for the unique topography of cognitive and behavioral features associated with this disorder.

    View details for DOI 10.1523/JNEUROSCI.5272-03.2004

    View details for Web of Science ID 000221654400013

    View details for PubMedID 15163693

  • Functional neuroanatomy of spatial orientation processing in Turner syndrome CEREBRAL CORTEX Kesler, S. R., Haberecht, M. F., Menon, V., Warsofsky, I. S., Dyer-Friedman, J., Neely, E. K., Reiss, A. L. 2004; 14 (2): 174-180


    Turner syndrome (TS), a neurogenetic disorder characterized by the absence of one X chromosome in a phenotypic female, is frequently associated with visuospatial impairments. We investigated the neural mechanisms underlying deficits in spatial orientation processing in TS. Thirteen subjects with TS and 13 age-matched typically developing controls underwent neuropsychological assessments and were scanned using functional MRI while they performed easy and difficult versions of a judgment of line orientation (JLO) task. Controls and subjects with TS activated parietal-occipital regions involved in spatial orientation during the JLO task. However, activation was significantly less in the TS group. Control subjects responded to increased task difficulty by recruiting executive frontal areas whereas subjects with TS did not activate alternate brain regions to meet increased task demands. Subjects with TS demonstrate activation deficits in parietal-occipital and frontal areas during the JLO task. Activation, and possibly deactivation, deficits in these areas may be responsible for the visuospatial deficits observed in females with TS.

    View details for DOI 10.1093/cercor/bhg116

    View details for Web of Science ID 000187975800006

    View details for PubMedID 14704214

  • Amygdala and hippocampal volumes in Turner syndrome: a high-resolution MRI study of X-monosomy NEUROPSYCHOLOGIA Kesler, S. R., Garrett, A., Bender, B., Yankowitz, J., Zeng, S. M., Reiss, A. L. 2004; 42 (14): 1971-1978


    Turner syndrome (TS) results from partial or complete X-monosomy and is characterized by deficits in visuospatial functioning as well as social cognition and memory. Neuroimaging studies have demonstrated volumetric differences in the parietal region of females with TS compared to controls. The present study examined amygdala and hippocampus morphology in an attempt to further understand the neural correlates of psychosocial and memory functioning in TS. Thirty females with TS age 7.6-33.3 years (mean = 14.7 +/- 6.4) and 29 age-matched controls (mean age = 14.8 +/- 5.9; range = 6.4-32.7) were scanned using high resolution MRI. Volumetric analyses of the MRI scans included whole brain segmentation and manual delineation of the amygdala and hippocampus. Compared to controls, participants with TS demonstrated significantly larger left amygdala gray matter volumes, irrespective of total cerebral tissue and age. Participants with TS also showed disproportionately reduced right hippocampal volumes, involving both gray and white matter. Amygdala and hippocampal volumes appear to be impacted by X-monosomy. Aberrant morphology in these regions may be related to the social cognition and memory deficits often experienced by individuals with TS. Further investigations of changes in medial temporal morphology associated with TS are warranted.

    View details for DOI 10.1016/j.neuropsychologia.2004.04.021

    View details for Web of Science ID 000224330500012

    View details for PubMedID 15381027

  • Effects of X-monosomy and X-linked imprinting on superior temporal gyrus morphology in Turner syndrome BIOLOGICAL PSYCHIATRY Kesler, S. R., Blasey, C. M., Brown, W. E., Yankowitz, J., Zeng, S. M., Bender, B. G., Reiss, A. L. 2003; 54 (6): 636-646


    Turner syndrome (TS) results from complete or partial monosomy X. The cognitive phenotype of TS involves preservation of verbal skills with visuospatial functioning deficits. The superior temporal gyrus (STG), which is involved in language capacities, has not been investigated in TS.The STG was measured in 30 female subjects (mean age = 14.73 +/- 6.41; range = 7.56-33.30) with TS and 30 age-matched control subjects (mean age = 14.63 +/- 5.90; range = 6.35-32.65) using volumetric magnetic resonance imaging analyses.-Right STG, including both gray and white matter volumes, was significantly larger in TS compared with control subjects. Overall left STG volume was not significantly different between groups, although left white matter volume was increased in the TS subjects. The TS subgroup with a maternally derived X chromosome (Xm) demonstrated more aberrant STG volumes compared with subjects with a paternally (Xp) derived X and control subjects. The difference in STG volumes between Xm and control subjects involved both white and gray matter. The Xm subjects differed from Xp subjects only in terms of gray matter.These findings suggest that X-monosomy and X-linked imprinting negatively affect STG development, possibly by disrupting neural pruning mechanisms.

    View details for DOI 10.1016/S0006-3223(03)00289-0

    View details for Web of Science ID 000185264700007

    View details for PubMedID 13129659

  • Premorbid intellectual functioning, education, and brain size in traumatic brain injury: An investigation of the cognitive reserve hypothesis APPLIED NEUROPSYCHOLOGY Kesler, S. R., Adams, H. F., Blasey, C. M., Bigler, E. D. 2003; 10 (3): 153-162


    Cognitive reserve theories have been postulated in an attempt to explain individual differences in functional outcome following cerebral insult or disease. These theories suggest that higher education and psychometric intelligence may preserve functional capacity regardless of injury or disease severity. This study investigated cognitive reserve in 25 participants with traumatic brain injury (TBI) using high-resolution magnetic resonance imaging (MRI) analyses. We examined the relationships between total intracranial volume (TICV), ventricle-tobrain ratio (VBR), education level, and standardized testing obtained prior to injury with post-injury cognitive outcome. Participants with lower post-injury IQ scores had significantly lower TICV values, irrespective of injury severity, and experienced significantly greater change in IQ from pre- to post-injury. TICV and education correctly predicted participants' post-injury IQ category ( Y 90 or < 90). However, premorbid standardized testing (PST) scores did not predict cognitive outcome. The results of this study suggest that larger premorbid brain volume and higher education level may decrease vulnerability to cognitive deficits following TBI, consistent with the notion of a cognitive reserve.

    View details for Web of Science ID 000189387500004

    View details for PubMedID 12890641

  • Brain development in Turner syndrome: a magnetic resonance imaging study PSYCHIATRY RESEARCH-NEUROIMAGING Brown, W. E., Kesler, S. R., Eliez, S., Warsofsky, I. S., Haberecht, M., Patwardhan, A., Ross, J. L., Neely, E. K., Zeng, S. M., Yankowitz, J., Reiss, A. L. 2002; 116 (3): 187-196


    Turner syndrome (TS) results from the absence of an X chromosome in females. This genetic condition is associated with specific cognitive deficits and variations in brain volumes. The goal of this study was to use high-resolution magnetic resonance imaging (MRI) to determine morphological variations in TS and to investigate the effects of parental origin of the X chromosome on brain development in TS. MRI brain scans were acquired from 26 girls with TS and 26 age- and gender-matched controls. Seventeen of the TS subjects had a maternally inherited X chromosome (Xm), and nine of the subjects had a paternally inherited X chromosome (Xp). Rater-blind morphometric analyses were conducted to compare tissue volume differences between girls with TS and controls. Three-way analyses were used to compare subgroups and controls. Subjects with TS demonstrated bilateral decreases in parietal gray and occipital white matter accompanied by increased cerebellar gray matter. Subjects with Xm showed decreased occipital white matter and increased cerebellar gray matter compared to controls. No differences were found in comparisons between subjects with Xp and controls or between subjects with Xm and Xp. Results suggest that X monosomy affects posterior cerebral and cerebellar anatomy in TS. While differences between comparisons of Xm and Xp to controls might suggest an imprinting effect, no significant differences were found when the two subgroups were directly compared to each other. Further investigation into the possible role of genomic imprinting is therefore warranted.

    View details for Web of Science ID 000180535800005

    View details for PubMedID 12477602

  • Verbal memory deficits associated with fornix atrophy in carbon monoxide poisoning JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY Kesler, S. R., Hopkins, R. O., Weaver, L. K., Blatter, D. D., Edge-Booth, H., Bigler, E. D. 2001; 7 (5): 640-646


    Magnetic resonance (MR) images and neuropsychological testing data of 69 carbon monoxide (CO) poisoned patients were prospectively obtained within 1 day of CO poisoning, two weeks and six months. CO patients' Day 1 cross-sectional fornix surface area measurements, corrected for head size by using a fornix-to-brain ratio (FBR), were compared to normal age and gender-matched controls. Additionally, a within-subjects analysis was performed comparing the mean areas between CO patients' Day 1, 2 weeks and 6-month FBR. The FBR was correlated with patients' neuropsychological data. There were no significant differences between CO patients' Day 1 fornix measurements compared to normal control subjects. However, significant atrophic changes in the fornix of CO poisoned patients occurred at two weeks with no progressive atrophy at 6 months. By 6 months, CO patients showed significant decline on tests of verbal memory (when practice effects were taken into account), whereas visual memory, processing speed and attention/concentration did not decline. This study indicates that CO results in brain damage and cognitive impairments in the absence of lesions and other neuroanatomic markers.

    View details for Web of Science ID 000169827900011

    View details for PubMedID 11459115

  • SPECT, MR and quantitative MR imaging: correlates with neuropsychological and psychological outcome in traumatic brain injury BRAIN INJURY Kesler, S. R., Adams, H. F., Bigler, E. D. 2000; 14 (10): 851-857


    This study examined the relative effectiveness of magnetic resonance (MR) imaging, single photon emission tomography (SPECT) and quantitative magnetic resonance (QMR) imaging in detecting brain abnormalities in 52 traumatically brain injured patients. The relationship between brain abnormalities and neuropsychological and psychological testing results was also investigated. Sixty-two per cent of patients had abnormal clinical MR findings, 57% had abnormal SPECT and 51% had abnormal QMR. Each neuroimaging modality detected brain abnormalities that the other two did not. Neuropsychological and psychological testing indicated significant memory impairments and subjective emotional distress even several years post-injury. Memory and intellectual impairments modestly but significantly correlated with the number of brain abnormalities indicated by all three imaging studies combined, as well as those detected individually by QMR and MR. SPECT abnormalities alone were not correlated with intellectual and memory outcome. Psychological distress was also related to the number of MR abnormalities, with most brain abnormalities being in the frontal areas.

    View details for Web of Science ID 000089902900001

    View details for PubMedID 11076132

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