Academic Appointments

Honors & Awards

  • White matter structure in Children with Autism, their siblings and controls, National Alliance for Research of Schizophrenia and Affective Disorders (NARSAD) (2005-2007)
  • Neural correlates of major depression with suicidal ideation in female adolescents, American Foundation for Suicide Prevention (AFSP) (2005-2007)
  • Brain white-matter pathways in sibling-pair offspring of parents with bipolar disorder, Child Health Research Program (CHRP), Stanford University School of Medicine (2008-2009)
  • White-matter pathways in sibling-pair offspring of parents with bipolar disorder, Child Health Research Program (CHRP), Stanford University School of Medicine (2008-2009)
  • Cortical folding complexity in children with autism, their autism-discordant siblings, and controls, Autism Speaks – Physician/Investigator Beginning Autism Research Award (2010-2011)
  • Identification of biomarkers for early diagnosis of Autism Spectrum Disorders (ASD), The Simons Foundation Autism Research Institute (SFARI) (2013-2015)


All Publications

  • Neonatal brain microstructure correlates of neurodevelopment and gait in preterm children 18-22 mo of age: an MRI and DTI study PEDIATRIC RESEARCH Rose, J., Cahill-Rowley, K., Vassar, R., Yeom, K. W., Stecher, X., Stevenson, D. K., Hintz, S. R., Barnea-Goraly, N. 2015; 78 (6): 700-708
  • Specific effect of the fragile-X mental retardation-1 gene (FMR1) on white matter microstructure BRITISH JOURNAL OF PSYCHIATRY Green, T., Barnea-Goraly, N., Raman, M., Hall, S. S., Lightbody, A. A., Bruno, J. L., Quintin, E., Reiss, A. L. 2015; 207 (2): 143-148


    Background Fragile-X syndrome (FXS) is a neurodevelopmental disorder associated with intellectual disability and neurobiological abnormalities including white matter microstructural differences. White matter differences have been found relative to neurotypical individuals. Aims To examine whether FXS white matter differences are related specifically to FXS or more generally to the presence of intellectual disability. Method We used voxel-based and tract-based analytic approaches to compare individuals with FXS (n = 40) with gender- and IQ-matched controls (n = 30). Results Individuals with FXS had increased fractional anisotropy and decreased radial diffusivity values compared with IQ-matched controls in the inferior longitudinal, inferior fronto-occipital and uncinate fasciculi. Conclusions The genetic variation associated with FXS affects white matter microstructure independently of overall IQ. White matter differences, found in FXS relative to IQ-matched controls, are distinct from reported differences relative to neurotypical controls. This underscores the need to consider cognitive ability differences when investigating white matter microstructure in neurodevelopmental disorders.

    View details for DOI 10.1192/bjp.bp.114.151654

    View details for Web of Science ID 000359180800009

    View details for PubMedID 25792692

  • Widespread white matter tract aberrations in youth with familial risk for bipolar disorder. Psychiatry research Roybal, D. J., Barnea-Goraly, N., Kelley, R., Bararpour, L., Howe, M. E., Reiss, A. L., Chang, K. D. 2015; 232 (2): 184-192


    Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis.

    View details for DOI 10.1016/j.pscychresns.2015.02.007

    View details for PubMedID 25779034

  • Widespread white matter tract aberrations in youth with familial risk for bipolar disorder PSYCHIATRY RESEARCH-NEUROIMAGING Roybal, D. J., Barnea-Goraly, N., Kelley, R., Bararpour, L., Howe, M. E., Reiss, A. L., Chang, K. D. 2015; 232 (2): 184-192
  • Identification of Neonatal White Matter on DTI: Influence of More Inclusive Thresholds for Atlas Segmentation PLOS ONE Vassar, R. L., Barnea-Goraly, N., Rose, J. 2014; 9 (12)
  • Altered Microstructure Within Social-Cognitive Brain Networks During Childhood in Williams Syndrome CEREBRAL CORTEX Haas, B. W., Barnea-Goraly, N., Sheau, K. E., Yamagata, B., Ullas, S., Reiss, A. L. 2014; 24 (10): 2796-2806


    Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ∼26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition.

    View details for DOI 10.1093/cercor/bht135

    View details for Web of Science ID 000343408200024

  • Brain microstructural development at near-term age in very-low-birth-weight preterm infants: An atlas-based diffusion imaging study NEUROIMAGE Rose, J., Vassar, R., Cahill-Rowley, K., Guzman, X. S., Stevenson, D. K., Barnea-Goraly, N. 2014; 86: 244-256


    At near-term age the brain undergoes rapid growth and development. Abnormalities identified during this period have been recognized as potential predictors of neurodevelopment in children born preterm. This study used diffusion tensor imaging (DTI) to examine white matter (WM) microstructure in very-low-birth-weight (VLBW) preterm infants to better understand regional WM developmental trajectories at near-term age. DTI scans were analyzed in a cross-sectional sample of 45 VLBW preterm infants (BW≤1500g, GA≤32weeks) within a cohort of 102 neonates admitted to the NICU and recruited to participate prior to standard-of-care MRI, from 2010 to 2011, 66/102 also had DTI. For inclusion in this analysis, 45 infants had DTI, no evidence of brain abnormality on MRI, and were scanned at PMA ≤40weeks (34.7-38.6). White matter microstructure was analyzed in 19 subcortical regions defined by DiffeoMap neonatal brain atlas, using threshold values of trace <0.006mm(2)s(-1) and FA >0.15. Regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and temporal-spatial trajectories of development were examined in relation to PMA and brain region location. Posterior regions within the corona radiata (CR), corpus callosum (CC), and internal capsule (IC) demonstrated significantly higher mean FA values compared to anterior regions. Posterior regions of the CR and IC demonstrated significantly lower RD values compared to anterior regions. Centrally located projection fibers demonstrated higher mean FA and lower RD values than peripheral regions including the posterior limb of the internal capsule (PLIC), cerebral peduncle, retrolenticular part of the IC, posterior thalamic radiation, and sagittal stratum. Centrally located association fibers of the external capsule had higher FA and lower RD than the more peripherally-located superior longitudinal fasciculus (SLF). A significant relationship between PMA-at-scan and FA, MD, and RD was demonstrated by a majority of regions, the strongest correlations were observed in the anterior limb of the internal capsule, a region undergoing early stages of myelination at near-term age, in which FA increased (r=.433, p=.003) and MD (r=-.545, p=.000) and RD (r=-.540, p=.000) decreased with PMA-at-scan. No correlation with PMA-at-scan was observed in the CC or SLF, regions that myelinate later in infancy. Regional patterns of higher FA and lower RD were observed at this near-term age, suggestive of more advanced microstructural development in posterior compared to anterior regions within the CR, CC, and IC and in central compared to peripheral WM structures. Evidence of region-specific rates of microstructural development was observed. Temporal-spatial patterns of WM microstructure development at near-term age have important implications for interpretation of near-term DTI and for identification of aberrations in typical developmental trajectories that may signal future impairment.

    View details for DOI 10.1016/j.neuroimage2013.09.053

    View details for Web of Science ID 000330335300026

    View details for PubMedID 24091089

  • Alterations in White Matter Structure in Young Children With Type 1 Diabetes DIABETES CARE Barnea-Goraly, N., Raman, M., Mazaika, P., Marzelli, M., Hershey, T., Weinzimer, S. A., Aye, T., Buckingham, B., Mauras, N., White, N. H., Fox, L. A., Tansey, M., Beck, R. W., Ruedy, K. J., Kollman, C., Cheng, P., Reiss, A. L. 2014; 37 (2): 332-340


    OBJECTIVE To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children. RESEARCH DESIGN AND METHODS Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition. RESULTS Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects. CONCLUSIONS These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.

    View details for DOI 10.2337/dc13-1388

    View details for Web of Science ID 000331072800018

  • High success rates of sedation-free brain MRI scanning in young children using simple subject preparation protocols with and without a commercial mock scanner-the Diabetes Research in Children Network (DirecNet) experience PEDIATRIC RADIOLOGY Barnea-Goraly, N., Weinzimer, S. A., Ruedy, K. J., Mauras, N., Beck, R. W., Marzelli, M. J., Mazaika, P. K., Aye, T., White, N. H., Tsalikian, E., Fox, L., Kollman, C., Cheng, P., Reiss, A. L. 2014; 44 (2): 181-186


    The ability to lie still in an MRI scanner is essential for obtaining usable image data. To reduce motion, young children are often sedated, adding significant cost and risk.We assessed the feasibility of using a simple and affordable behavioral desensitization program to yield high-quality brain MRI scans in sedation-free children.222 children (4-9.9 years), 147 with type 1 diabetes and 75 age-matched non-diabetic controls, participated in a multi-site study focused on effects of type 1 diabetes on the developing brain. T1-weighted and diffusion-weighted imaging (DWI) MRI scans were performed. All children underwent behavioral training and practice MRI sessions using either a commercial MRI simulator or an inexpensive mock scanner consisting of a toy tunnel, vibrating mat, and video player to simulate the sounds and feel of the MRI scanner.205 children (92.3%), mean age 7 ± 1.7 years had high-quality T1-W scans and 174 (78.4%) had high-quality diffusion-weighted scans after the first scan session. With a second scan session, success rates were 100% and 92.5% for T1-and diffusion-weighted scans, respectively. Success rates did not differ between children with type 1 diabetes and children without diabetes, or between centers using a commercial MRI scan simulator and those using the inexpensive mock scanner.Behavioral training can lead to a high success rate for obtaining high-quality T1-and diffusion-weighted brain images from a young population without sedation.

    View details for DOI 10.1007/s00247-013-2798-7

    View details for Web of Science ID 000330987900007

    View details for PubMedID 24096802

  • A preliminary longitudinal volumetric MRI study of amygdala and hippocampal volumes in autism PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY Barnea-Goraly, N., Frazier, T. W., Piacenza, L., Minshew, N. J., Keshavan, M. S., Reiss, A. L., Hardan, A. Y. 2014; 48: 124-128


    Previous studies suggest that amygdala volume, when compared with healthy controls, is increased in young children with autism, is unchanged in cohorts of older youth, and is smaller in adults. Hippocampal volume, however, does not appear to have age-related changes, and it is unclear whether individuals with autism have volumetric differences in this structure. The goal of this pilot investigation is to characterize the developmental trajectories of the amygdala and hippocampus in children with autism between the ages of 8 and 14years and to examine clinical correlates of volume change.Twenty-three children with autism and 23 controls between the ages of 8 and 12 underwent a magnetic resonance imaging procedure of the brain (T1-weighted) at two time points. Nine children with autism and 14 controls had good quality scans from both time points; however, all usable scans from all subjects (15 children with autism and 22 controls) were included in a mixed effect analysis. Regression models were used to estimate group differences in amygdala and hippocampal volumes. Changes in amygdala and hippocampal volumes (Time 2-Time 1) were correlated with clinical severity measures.Amygdala volume changes with time were similar between the two groups. Within the autism group, right amygdala volume change was correlated with the ability to establish appropriate eye contact. Right hippocampal volume was significantly increased in the autism group when compared with controls. Differences in right hippocampal volume change with time between the two groups approached significance.This study provides preliminary evidence of normalization of amygdala volumes in late childhood and adolescence. It also suggests that hippocampal volumetric differences may exist in autism in late childhood and adolescence.

    View details for DOI 10.1016/j.pnpbp.2013.09.010

    View details for Web of Science ID 000328074200018

    View details for PubMedID 24075822

  • Neuroanatomical Correlates of Dysglycemia in Young Children With Type 1 Diabetes DIABETES Marzelli, M. J., Mazaika, P. K., Barnea-Goraly, N., Hershey, T., Tsalikian, E., Tamborlane, W., Mauras, N., White, N. H., Buckingham, B., Beck, R. W., Ruedy, K. J., Kollman, C., Cheng, P., Reiss, A. L. 2014; 63 (1): 343-353


    Studies of brain structure in type 1 diabetes (T1D) describe widespread neuroanatomical differences related to exposure to glycemic dysregulation in adults and adolescents. In this study, we investigate the neuroanatomical correlates of dysglycemia in very young children with early-onset T1D. Structural magnetic resonance images of the brain were acquired in 142 children with T1D and 68 age-matched control subjects (mean age 7.0 ± 1.7 years) on six identical scanners. Whole-brain volumetric analyses were conducted using voxel-based morphometry to detect regional differences between groups and to investigate correlations between regional brain volumes and measures of glycemic exposure (including data from continuous glucose monitoring). Relative to control subjects, the T1D group displayed decreased gray matter volume (GMV) in bilateral occipital and cerebellar regions (P < 0.001) and increased GMV in the left inferior prefrontal, insula, and temporal pole regions (P = 0.002). Within the T1D group, hyperglycemic exposure was associated with decreased GMV in medial frontal and temporal-occipital regions and increased GMV in lateral prefrontal regions. Cognitive correlations of intelligence quotient to GMV were found in cerebellar-occipital regions and medial prefrontal cortex for control subjects, as expected, but not for the T1D group. Thus, early-onset T1D affects regions of the brain that are associated with typical cognitive development.

    View details for DOI 10.2337/db13-0179

    View details for Web of Science ID 000328680400040

  • Identification of neonatal white matter on DTI: influence of more inclusive thresholds for atlas segmentation. PloS one Vassar, R. L., Barnea-Goraly, N., Rose, J. 2014; 9 (12)


    Semi-automated diffusion tensor imaging (DTI) analysis of white matter (WM) microstructure offers a clinically feasible technique to assess neonatal brain development and provide early prognosis, but is limited by variable methods and insufficient evidence regarding optimal parameters. The purpose of this research was to investigate the influence of threshold values on semi-automated, atlas-based brain segmentation in very-low-birth-weight (VLBW) preterm infants at near-term age.DTI scans were analyzed from 45 VLBW preterm neonates at near-term-age with no brain abnormalities evident on MRI. Brain regions were selected with a neonatal brain atlas and threshold values: trace <0.006 mm2/s, fractional anisotropy (FA)>0.15, FA>0.20, and FA>0.25. Relative regional volumes, FA, axial diffusivity (AD), and radial diffusivity (RD) were compared for twelve WM regions.Near-term brain regions demonstrated differential effects from segmentation with the three FA thresholds. Regional DTI values and volumes selected in the PLIC, CereP, and RLC varied the least with the application of different FA thresholds. Overall, application of higher FA thresholds significantly reduced brain region volume selected, increased variability, and resulted in higher FA and lower RD values. The lower threshold FA>0.15 selected 78±21% of original volumes segmented by the atlas, compared to 38±12% using threshold FA>0.25.Results indicate substantial and differential effects of atlas-based DTI threshold parameters on regional volume and diffusion scalars. A lower, more inclusive FA threshold than typically applied for adults is suggested for consistent analysis of WM regions in neonates.

    View details for DOI 10.1371/journal.pone.0115426

    View details for PubMedID 25506943

  • Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants NEUROIMAGE-CLINICAL Rose, J., Vassar, R., Cahill-Rowley, K., Guzman, X. S., Hintz, S. R., Stevenson, D. K., Barnea-Goraly, N. 2014; 5: 169-177


    Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

    View details for DOI 10.1016/j.nicl.2014.05.013

    View details for Web of Science ID 000349667800020

    View details for PubMedID 25068107

  • White Matter Aberrations in Prepubertal Estrogen-Naive Girls with Monosomic Turner Syndrome CEREBRAL CORTEX Yamagata, B., Barnea-Goraly, N., Marzelli, M. J., Park, Y., Hong, D. S., Mimura, M., Reiss, A. L. 2012; 22 (12): 2761-2768


    Turner syndrome (TS) offers a unique opportunity to investigate associations among genes, the brain, and cognitive phenotypes. In this study, we used 3 complementary analyses of diffusion tensor imaging (DTI) data (whole brain, region of interest, and fiber tractography) and a whole brain volumetric imaging technique to investigate white matter (WM) structure in prepubertal, nonmosaic, estrogen-naive girls with TS compared with age and sex matched typically developing controls. The TS group demonstrated significant WM aberrations in brain regions implicated in visuospatial abilities, face processing, and sensorimotor and social abilities compared with controls. Extensive spatial overlap between regions of aberrant WM structure (from DTI) and regions of aberrant WM volume were observed in TS. Our findings indicate that complete absence of an X chromosome in young females (prior to receiving exogenous estrogen) is associated with WM aberrations in specific regions implicated in characteristic cognitive features of TS.

    View details for DOI 10.1093/cercor/bhr355

    View details for Web of Science ID 000310965200005

    View details for PubMedID 22172580

  • White Matter Structural Differences in Young Children With Type 1 Diabetes: A Diffusion Tensor Imaging Study DIABETES CARE Aye, T., Barnea-Goraly, N., Ambler, C., Hoang, S., Schleifer, K., Park, Y., Drobny, J., Wilson, D. M., Reiss, A. L., Buckingham, B. A. 2012; 35 (11): 2167-2173


    To detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes.Children, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans.Compared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher, time-weighted HbA(1c) value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).Children with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA(1c) values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.

    View details for DOI 10.2337/dc12-0017

    View details for Web of Science ID 000311424100015

    View details for PubMedID 22966090

  • Diffusion tensor imaging reveals white matter abnormalities in Attention-Deficit/Hyperactivity Disorder PSYCHIATRY RESEARCH-NEUROIMAGING Tamm, L., Barnea-Goraly, N., Reiss, A. L. 2012; 202 (2): 150-154


    The specific brain structures or neural mechanisms underlying dysfunction in individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) are not well established, particularly in regard to white matter (WM). Diffusion tensor imaging (DTI) was used to investigate WM in 12 adolescent males diagnosed with ADHD only and 12 typically developing controls (group matched; mean age=15.64 years, SD=1.15). In addition to fractional anisotropy (FA), we also examined axial and radial diffusivity (AD and RD) in an effort to help elucidate conflicting findings suggesting that both lower and higher FA values are characteristic of ADHD. Tract-based spatial statistics and voxel-wide analyses were conducted on the data utilizing a pre-frontal mask to enable focus on fronto-striatal and prefrontal pathways. Adolescents with ADHD had significantly higher FA and AD values in fronto-striatal pathways compared with controls. No differences were observed for RD. These results contribute to the growing literature implicating prefrontal WM variations in neuropsychiatric disorders, and are consistent with findings suggesting a role for fronto-striatal pathways in ADHD pathophysiology.

    View details for DOI 10.1016/j.pscychresns.2012.04.001

    View details for Web of Science ID 000307424600009

    View details for PubMedID 22703620

  • Preliminary evidence of abnormal white matter related to the fusiform gyrus in Williams syndrome: a diffusion tensor imaging tractography study GENES BRAIN AND BEHAVIOR Haas, B. W., Hoeft, F., Barnea-Goraly, N., Golarai, G., Bellugi, U., Reiss, A. L. 2012; 11 (1): 62-68


    Williams syndrome (WS) is a genetic condition caused by a hemizygous microdeletion on chromosome 7q11.23. WS is characterized by a distinctive social phenotype composed of increased drive toward social engagement and attention toward faces. In addition, individuals with WS exhibit abnormal structure and function of brain regions important for the processing of faces such as the fusiform gyrus. This study was designed to investigate if white matter tracts related to the fusiform gyrus in WS exhibit abnormal structural integrity as compared to typically developing (TD; age matched) and developmentally delayed (DD; intelligence quotient matched) controls. Using diffusion tensor imaging data collected from 40 (20 WS, 10 TD and 10 DD) participants, white matter fibers were reconstructed that project through the fusiform gyrus and two control regions (caudate and the genu of the corpus callosum). Macro-structural integrity was assessed by calculating the total volume of reconstructed fibers and micro-structural integrity was assessed by calculating fractional anisotropy (FA) and fiber density index (FDi) of reconstructed fibers. WS participants, as compared to controls, exhibited an increase in the volume of reconstructed fibers and an increase in FA and FDi for fibers projecting through the fusiform gyrus. No between-group differences were observed in the fibers that project through the control regions. Although preliminary, these results provide further evidence that the brain anatomy important for processing faces is abnormal in WS.

    View details for DOI 10.1111/j.1601-183X.2011.00733.x

    View details for Web of Science ID 000298989400006

    View details for PubMedID 21939500

  • Biological Evidence for a Neurodevelopmental Model of Pediatric Bipolar Disorder ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES Roybal, D. J., Singh, M. K., Cosgrove, V. E., Howe, M., Kelley, R., Barnea-Goraly, N., Chang, K. D. 2012; 49 (1): 28-43
  • Advances in clinical neuroimaging: implications for autism spectrum disorders. Expert opinion on medical diagnostics Barnea-Goraly, N., Hardan, A. 2011; 5 (6): 475-482


    Introduction: Neuroimaging research has been labeled 'modern phrenology', suggesting that this line of research does not advance our knowledge of neuropsychiatric disorders beyond spatial localization of brain abnormalities. In this paper, we argue against this claim and discuss the application of neuroimaging techniques in neuropsychiatric disorders in general and in autism spectrum disorders (ASDs) in particular. Areas covered: Recent neuroimaging literature, and its role in increasing our understanding of the neurobiologic underpinnings of several disorders, is reviewed. Neuroimaging is discussed, with respect to the identification of at-risk individuals, prediction of treatment response and development of new treatment approaches. Furthermore, the authors discuss the clinical relevance of such methodologies in the context of autism. Specifically, the article shows how recent advances in the understanding of psychiatric and neurologic disorders, through the use of neuroimaging techniques, can be beneficially applied to the unique needs of ASD diagnosis and treatment. Expert opinion: This is an exciting time for neuroimaging research. Studies have already shown the potential of neuroimaging to better inform clinicians about disorders such as depression, anxiety and psychosis. The application of neuroimaging to ASD may provide new insight into the disorder and help deliver better care for affected individuals.

    View details for DOI 10.1517/17530059.2011.595785

    View details for PubMedID 23484746

  • Similar White Matter Aberrations in Children With Autism and Their Unaffected Siblings A Diffusion Tensor Imaging Study Using Tract-Based Spatial Statistics ARCHIVES OF GENERAL PSYCHIATRY Barnea-Goraly, N., Lotspeich, L. J., Reiss, A. L. 2010; 67 (10): 1052-1060


    Autism is a neurobiological condition with a strong genetic component. Recent diffusion tensor imaging (DTI) studies have indicated that white matter structure is aberrant in autism. To date, white matter structure has not been assessed in family members of children with autism.To determine whether white matter structure is aberrant in children with autism and their unaffected siblings compared with controls, and to test the hypothesis that white matter structure in autism is correlated with autism spectrum symptomatology.Cross-sectional, case-control, voxel-based, whole-brain DTI analysis using Tract-Based Spatial Statistics.University research center. Patients  A sample of 37 children: 13 subjects with autism, 13 of their unaffected siblings, and 11 controls. Controls were age- and intelligence quotient-matched to the unaffected siblings; all groups were age matched. Main Outcome Measure  Fractional anisotropy (FA) and axial and radial diffusivities. In addition, behavioral correlation analyses were conducted using the Autism Diagnostic Interview and Autism Diagnostic Observation Schedule subscales and FA values, as well as axial diffusivity values in the autism group.Compared with the control group, both the autism and sibling groups had widespread, significantly reduced white matter FA values (P ? .05, corrected) in the frontal parietal and temporal lobes and included, but were not restricted to, regions known to be important for social cognition. Within regions of reduced FA, significant reductions in axial diffusivity, but not radial diffusivity, were observed. There were no significant differences in white matter structure between the autism and sibling groups. There were no significant correlations between autism symptomatology and white matter FA or axial diffusivity.Our findings suggest that white matter structure may represent a marker of genetic risk for autism or vulnerability to development of this disorder.

    View details for Web of Science ID 000282917400009

    View details for PubMedID 20921121

  • Limbic and Corpus Callosum Aberrations in Adolescents with Bipolar Disorder: A Tract-Based Spatial Statistics Analysis BIOLOGICAL PSYCHIATRY Barnea-Goraly, N., Chang, K. D., Karchemskiy, A., Howe, M. E., Reiss, A. L. 2009; 66 (3): 238-244


    Bipolar disorder (BD) is a common and debilitating condition, often beginning in adolescence. Converging evidence from genetic and neuroimaging studies indicates that white matter abnormalities may be involved in BD. In this study, we investigated white matter structure in adolescents with familial bipolar disorder using diffusion tensor imaging (DTI) and a whole brain analysis.We analyzed DTI images using tract-based spatial statistics (TBSS), a whole-brain voxel-by-voxel analysis, to investigate white matter structure in 21 adolescents with BD, who also were offspring of at least one parent with BD, and 18 age- and IQ-matched control subjects. Fractional anisotropy (FA; a measure of diffusion anisotropy), trace values (average diffusivity), and apparent diffusion coefficient (ADC; a measure of overall diffusivity) were used as variables in this analysis. In a post hoc analysis, we correlated between FA values, behavioral measures, and medication exposure.Adolescents with BD had lower FA values than control subjects in the fornix, the left mid-posterior cingulate gyrus, throughout the corpus callosum, in fibers extending from the fornix to the thalamus, and in parietal and occipital corona radiata bilaterally. There were no significant between-group differences in trace or ADC values and no significant correlation between behavioral measures, medication exposure, and FA values.Significant white matter tract alterations in adolescents with BD were observed in regions involved in emotional, behavioral, and cognitive regulation. These results suggest that alterations in white matter are present early in the course of disease in familial BD.

    View details for DOI 10.1016/j.biopsych.2009.02.025

    View details for Web of Science ID 000267961600007

    View details for PubMedID 19389661

  • Early white-matter abnormalities of the ventral frontostriatal pathway in fragile X syndrome DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Haas, B. W., Barnea-Goraly, N., Lightbody, A. A., Patnaik, S. S., Hoeft, F., Hazlett, H., Piven, J., Reiss, A. L. 2009; 51 (8): 593-599


    Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development.In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n=17; mean age 2y 9mo, SD 7mo, range 1y 7mo-3y 10mo), and two age-matched comparison groups: (1) typically developing (n=13; mean age 2y 3mo, SD 7mo, range 1y 7mo-3y 6mo) and (2) developmentally delayed (n=8; mean age 3y, SD 4mo, range 2y 9mo-3y 8mo).We observed that young males with fragile X syndrome exhibited increased density of DTI reconstructed fibers than those in the typically developing (p=0.001) and developmentally delayed (p=0.001) groups. Aberrant white-matter structure was localized in the left ventral frontostriatal pathway. Greater relative fiber density was found to be associated with lower IQ (Mullen composite scores) in the typically developing group (p=0.008).These data suggest that diminished or absent fragile X mental retardation 1 protein expression can selectively alter white-matter anatomy during early brain development and, in particular, neural pathways. The results also point to an early neurobiological marker for an important component of cognitive dysfunction associated with fragile X syndrome.

    View details for DOI 10.1111/j.1469-8749.2009.03295.x

    View details for Web of Science ID 000268029100006

    View details for PubMedID 19416325

  • More is not always better: Increased fractional Anisotropy of superior longitudinal fasciculus associated with poor Visuospatial abilities in Williams syndrome JOURNAL OF NEUROSCIENCE Hoeft, F., Barnea-Goraly, N., Haas, B. W., Golarai, G., Ng, D., Mills, D., Korenberg, J., Bellugi, U., Galaburda, A., Reiss, A. L. 2007; 27 (44): 11960-11965


    We used diffusion tensor imaging to examine white matter integrity in the dorsal and ventral streams among individuals with Williams syndrome (WS) compared with two control groups (typically developing and developmentally delayed) and using three separate analysis methods (whole brain, region of interest, and fiber tractography). All analysis methods consistently showed that fractional anisotropy (FA; a measure of microstructural integrity) was higher in the right superior longitudinal fasciculus (SLF) in WS compared with both control groups. There was a significant association with deficits in visuospatial construction and higher FA in WS individuals. Comparable increases in FA across analytic methods were not observed in the left SLF or the bilateral inferior longitudinal fasciculus in WS subjects. Together, these findings suggest a specific role of right SLF abnormality in visuospatial construction deficits in WS.

    View details for DOI 10.1523/JNEUROSCI.3591-07.2007

    View details for Web of Science ID 000250577600025

    View details for PubMedID 17978036

  • Will neuroimaging ever be used to diagnose pediatric bipolar disorder? DEVELOPMENT AND PSYCHOPATHOLOGY Chang, K., Adleman, N., Wagner, C., Barnea-Goraly, N., Garrett, A. 2006; 18 (4): 1133-1146


    There is a great need for discovery of biological markers that could be used diagnostically for pediatric onset disorders, particularly those with potentially confusing phenomenology such as pediatric-onset bipolar disorder (BD). Obtaining these markers would help overcome current subjective diagnostic techniques of relying on parent and child interview and symptomatic history. Brain imaging may be the most logical choice for a diagnostic tool, and certain neurobiological abnormalities have already been found in pediatric BD. However, much work remains to be done before neuroimaging can be used reliably to diagnose this disorder, and because of the nature of BD and the limitations of imaging technology and technique, neuroimaging will likely at most be only a diagnostic aide in the near future. In this paper we discuss the characteristics of pediatric BD that complicate the use of biological markers as diagnostic tools, how neuroimaging techniques have been used to study pediatric BD so far, and the limitations and potential of such techniques for future diagnostic use.

    View details for DOI 10.1017/S0954579406060548

    View details for Web of Science ID 000241933300009

    View details for PubMedID 17064431

  • 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

  • White matter development during childhood and adolescence: A cross-sectional diffusion tensor imaging study CEREBRAL CORTEX Barnea-Goraly, N., Menon, V., Eckert, M., Tamm, L., Bammer, R., Karchemskiy, A., Dant, C. C., Reiss, A. L. 2005; 15 (12): 1848-1854


    Maturation of brain white matter pathways is an important factor in cognitive, behavioral, emotional and motor development during childhood and adolescence. In this study, we investigate white matter maturation as reflected by changes in anisotropy and white matter density with age. Thirty-four children and adolescents aged 6-19 years received diffusion-weighted magnetic resonance imaging scans. Among these, 30 children and adolescents also received high-resolution T1-weighed anatomical scans. A linear regression model was used to correlate fractional anisotropy (FA) values with age on a voxel-by-voxel basis. Within the regions that showed significant FA changes with age, a post hoc analysis was performed to investigate white matter density changes. With increasing age, FA values increased in prefrontal regions, in the internal capsule as well as in basal ganglia and thalamic pathways, the ventral visual pathways, and the corpus callosum. The posterior limb of the internal capsule, intrathalamic connections, and the corpus callosum showed the most significant overlaps between white matter density and FA changes with age. This study demonstrates that during childhood and adolescence, white matter anisotropy changes in brain regions that are important for attention, motor skills, cognitive ability, and memory. This typical developmental trajectory may be altered in individuals with disorders of development, cognition and behavior.

    View details for DOI 10.1093/cercor/bhi062

    View details for Web of Science ID 000233217300002

    View details for PubMedID 15758200

  • Arithmetic ability and parietal alterations: A diffusion tensor imaging study in Velocardiofacial syndrome COGNITIVE BRAIN RESEARCH Barnea-Goraly, N., Eliez, S., Menon, V., Bammer, R., Reiss, A. L. 2005; 25 (3): 735-740


    Velocardiofacial syndrome (VCFS) is a congenital anomaly that causes somatic as well as cognitive and psychiatric impairments. Previous studies have found specific deficits in arithmetic abilities in subjects with VCFS. In this study, we investigated whether abnormalities in white matter pathways are correlated with reduced arithmetic ability. Nineteen individuals with VCFS aged 7-19 years received diffusion-weighted magnetic resonance imaging (MRI) scans. A linear regression model was used to correlate fractional anisotropy (FA) values with scores of the arithmetic subscale on the WISC/WAIS on a voxel-by-voxel basis, after covarying for any IQ- and age-related effects. There was a statistically significant positive correlation between the arithmetic score on the WISC/WAIS and FA values in white matter tracts adjacent to the left supramarginal and angular gyri, as well as along the left intraparietal sulcus. Inferior parietal lobe white matter structural aberrations may contribute to reduced arithmetic ability in VCFS.

    View details for DOI 10.1016/j.cogbrainres.2005.09.013

    View details for Web of Science ID 000234236500014

    View details for PubMedID 16260124

  • Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder BIOLOGICAL PSYCHIATRY Chang, K., Barnea-Goraly, N., Karchemskiy, A., Simeonova, D. I., Barnes, P., Ketter, T., Reiss, A. L. 2005; 58 (3): 197-203


    Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects.Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH.After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects.Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.

    View details for DOI 10.1016/j.biopsych.2005.03.039

    View details for Web of Science ID 000231057100003

    View details for PubMedID 16084840

  • Reduced amygdalar gray matter volume in familial pediatric bipolar disorder JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY Chang, K., Karchemskiy, A., Barnea-Goraly, N., Garrett, A., Simeonova, D. I., Reiss, A. 2005; 44 (6): 565-573


    Subcortical limbic structures have been proposed to be involved in the pathophysiology of adult and pediatric bipolar disorder (BD). We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls.Twenty children and adolescents with BD I (mean age = 14.6 years, four females) and 20 healthy age, gender, and IQ-matched controls underwent high-resolution magnetic resonance imaging at 3 T. Patients were mostly euthymic and most were taking medications. Amygdala, hippocampus, thalamus, and caudate volumes were determined by manual tracings from researchers blinded to diagnosis. Analyses of covariance were performed, with total brain volume, age, and gender as covariates.No differences were found in the volumes of hippocampus, caudate, and thalamus between subjects with BD and controls. Subjects with BD had smaller volumes in the left and right amygdala, driven by reductions in gray matter volume. Exploratory analyses revealed that subjects with BD with past lithium or valproate exposure tended to have greater amygdalar gray matter volume than subjects with BD without such exposure.Children and adolescents with early-onset BD may have reduced amygdalar volumes, consistent with other studies in this population. Prolonged medication exposure to lithium or valproate may account for findings in adults with BD of increased amygdalar volume relative to controls.

    View details for DOI 10.1097/01.chi.0000159948.75136.0d

    View details for Web of Science ID 000229245600011

    View details for PubMedID 15908839

  • White matter structure in autism: Preliminary evidence from diffusion tensor imaging BIOLOGICAL PSYCHIATRY Barnea-Goraly, N., Kwon, H., Menon, V., Eliez, S., Lotspeich, L., Reiss, A. L. 2004; 55 (3): 323-326


    Individuals with autism have severe difficulties in social communication and relationships. Prior studies have suggested that abnormal connections between brain regions important for social cognition may contribute to the social deficits seen in autism.In this study, we used diffusion tensor imaging to investigate white matter structure in seven male children and adolescents with autism and nine age-, gender-, and IQ-matched control subjects.Reduced fractional anisotropy (FA) values were observed in white matter adjacent to the ventromedial prefrontal cortices and in the anterior cingulate gyri as well as in the temporoparietal junctions. Additional clusters of reduced FA values were seen adjacent to the superior temporal sulcus bilaterally, in the temporal lobes approaching the amygdala bilaterally, in occipitotemporal tracts, and in the corpus callosum.Disruption of white matter tracts between regions implicated in social functioning may contribute to impaired social cognition in autism.

    View details for DOI 10.1016/j.biopsych.2003.10.022

    View details for Web of Science ID 000188434000019

    View details for PubMedID 14744477

  • Review of magnetic resonance imaging and spectroscopy studies in children with bipolar disorder. Expert review of neurotherapeutics Adleman, N. E., Barnea-Goraly, N., Chang, K. D. 2004; 4 (1): 69-77


    Pediatric bipolar disorder is a serious condition that affects a child's ability to function normally during important developmental stages. Pediatric bipolar disorder often presents with a different symptom complex than adult-onset bipolar disorder, including higher rates of irritability and rapid cycling. Due to these differences, it is important to understand the neural substrates of the disease as it presents in children, especially when compared with adults. Understanding the brain abnormalities associated with pediatric bipolar disorder may provide much needed markers useful in diagnosing childhood-onset bipolar disorder, give insight into the neurobiological etiology of the disorder and lead to more effective treatments. Currently, there has been little neuroimaging research into pediatric bipolar disorder, specifically with regards to brain function. This review summarizes the neurobiological research that has been conducted on childhood- and adolescent-onset bipolar disorder using magnetic resonance technology. Future directions of research needed in this area also are discussed in the context of the existing literature.

    View details for PubMedID 15853617

  • Investigation of white matter structure in velocardiofacial syndrome: A diffusion tensor imaging study AMERICAN JOURNAL OF PSYCHIATRY Barnea-Goraly, N., Menon, V., Krasnow, B., Ko, A., Reiss, A., Eliez, S. 2003; 160 (10): 1863-1869


    Velocardiofacial syndrome, caused by a deletion on chromosome 22q11.2, is often accompanied by cognitive, behavioral, and psychiatric impairments. Specifically, velocardiofacial syndrome has been proposed as a disease model for a genetically mediated subtype of schizophrenia. Velocardiofacial syndrome is also known to affect brain structure. The most prominent structural findings in velocardiofacial syndrome are reduced white matter volumes. However, the structure of white matter and extent of specific regional involvement in this syndrome have never been investigated. The current study used diffusion tensor imaging to investigate white matter structure in children and young adults with velocardiofacial syndrome.Nineteen participants with velocardiofacial syndrome and 19 age- and gender-matched comparison subjects underwent diffusion-weighted magnetic resonance imaging scans. Whole brain voxel-by-voxel analyses were conducted to investigate white matter fractional anisotropy differences between the groups.Relative to the comparison group, the velocardiofacial syndrome group had reduced white matter anisotropy in the frontal, parietal, and temporal regions as well as in tracts connecting the frontal and temporal lobes.This study demonstrates that alterations of white matter tract structure occur in velocardiofacial syndrome. Reduced white matter anisotropy was observed in individuals with velocardiofacial syndrome in areas previously implicated in the neurocognitive phenotype of velocardiofacial syndrome. The finding of aberrant parietal white matter tracts as well as aberrant frontotemporal connectivity in velocardiofacial syndrome and in previous schizophrenia studies may be associated with increased vulnerability for development of psychotic symptoms.

    View details for Web of Science ID 000185880300024

    View details for PubMedID 14514502

  • Decreased N-acetylaspartate in children with familial bipolar disorder BIOLOGICAL PSYCHIATRY Chang, K., Adleman, N., Dienes, K., Barnea-Goraly, N., Reiss, A., Ketter, T. 2003; 53 (11): 1059-1065


    Relatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder.Subjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3) voxels placed in left and right dorsolateral prefrontal cortex.Bipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline levels were found.Children and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.

    View details for DOI 10.1016/S0006-3223(02)01744-4

    View details for Web of Science ID 000183339900016

    View details for PubMedID 12788251

  • White matter tract alterations in fragile X syndrome: Preliminary evidence from diffusion tensor imaging AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS Barnea-Goraly, N., Eliez, S., Hedeus, M., Menon, V., White, C. D., Moseley, M., Reiss, A. L. 2003; 118B (1): 81-88


    Fragile X syndrome, the most common form of hereditary mental retardation, causes disruption in the development of dendrites and synapses, the targets for axonal growth in the central nervous system. This disruption could potentially affect the development, wiring, and targeting of axons. The current study utilized diffusion tensor imaging (DTI) to investigate whether white matter tract integrity and connectivity are altered in fragile X syndrome. Ten females with a diagnosis of fragile X syndrome and ten, age matched, female control subjects underwent diffusion weighted MRI scans. A whole brain analysis of fractional anisotropy (FA) values was performed using statistical parametric mapping (SPM). A follow-up, regions-of-interest analysis also was conducted. Relative to controls, females with fragile X exhibited lower FA values in white matter in fronto-striatal pathways, as well as in parietal sensory-motor tracts. This preliminary study suggests that regionally specific alterations of white matter integrity occur in females with fragile X. Aberrant white matter connectivity in these regions is consistent with the profile of cognitive and behavioral features of fragile X syndrome, and potentially provide additional insight into the detrimental effects of suboptimal levels of FMRP in the developing brain.

    View details for DOI 10.1002/ajmg.b.10035

    View details for Web of Science ID 000182401800017

    View details for PubMedID 12627472

  • Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2) BIOLOGICAL PSYCHIATRY Eliez, S., Barnea-Goraly, N., Schmitt, J. E., Liu, Y., Reiss, A. L. 2002; 52 (1): 68-70


    This study evaluated differences in caudate volumes in subjects with velo-cardio-facial syndrome due to a 22q11.2 (22qDS) deletion. Because psychosis is observed in 30% of adult subjects with 22qDS, this neurogenetic disorder could represent a putative model for a genetically mediated subtype of schizophrenia.Caudate volumes were measured on high-resolution magnetic resonance images in 30 children and adolescents with 22qDS and 30 gender- and age-matched normal comparison subjects.Caudate head volumes were increased in the 22qDS group independent of neuroleptic medications. Subjects with 22qDS also displayed an abnormal pattern of asymmetry in the anterior caudate, with left side greater than right.Alterations in the basal ganglia circuitry have been implicated in learning, cognitive, and behavioral problems in children and therefore could be involved in the expression of the neurobehavioral phenotype expressed by subjects with 22qDS. Abnormal caudate volume is a neurodevelopmental feature shared with schizophrenia, further establishing 22qDS as a potential neurodevelopmental model for this disorder.

    View details for Web of Science ID 000176340700009

    View details for PubMedID 12079732