Joseph Biederman

YNICL Journal 2020 Journal Article

Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study

• Yuwen Hung
• Mai Uchida
• Schuyler L. Gaillard
• Hilary Woodworth
• Caroline Kelberman
• James Capella
• Kelly Kadlec
• Mathias Goncalves

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.

YNICL Journal 2016 Journal Article

Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain

• Aaron T. Mattfeld
• Susan Whitfield-Gabrieli
• Joseph Biederman
• Thomas Spencer
• Ariel Brown
• Ronna Fried
• John D.E. Gabrieli

Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

YNICL Journal 2015 Journal Article

Functional and structural brain correlates of risk for major depression in children with familial depression

• Xiaoqian J. Chai
• Dina Hirshfeld-Becker
• Joseph Biederman
• Mai Uchida
• Oliver Doehrmann
• Julia A. Leonard
• John Salvatore
• Tara Kenworthy

Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression.

YNICL Journal 2015 Journal Article

Postural sway and regional cerebellar volume in adults with attention-deficit/hyperactivity disorder

• Michael J. Hove
• Thomas A. Zeffiro
• Joseph Biederman
• Zhi Li
• Jeremy Schmahmann
• Eve M. Valera

OBJECTIVE: Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD. METHOD: In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board. RESULTS: Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX). CONCLUSION: These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate.

YNIMG Journal 2006 Journal Article

Human cerebral cortex: A system for the integration of volume- and surface-based representations

• Nikos Makris
• Jonathan Kaiser
• Christian Haselgrove
• Larry J. Seidman
• Joseph Biederman
• Denise Boriel
• Eve M. Valera
• George M. Papadimitriou

We describe an MRI-based system for topological analysis followed by measurements of topographic features for the human cerebral cortex that takes as its starting point volumetric segmentation data. This permits interoperation between volume-based and surface-based topographic analysis and extends the functionality of many existing segmentation schemes. We demonstrate the utility of these operations in individual as well as to group analysis. The methodology integrates analyses of cortical segmentation data generated by manual and semi-automated volumetric morphometry routines (such as the program cardviews) with the procedures of the FreeSurfer program to generate a cortical ribbon of the cerebrum and perform cortical topographic measurements (including thickness, surface area and curvature) in individual subjects as well as in subject populations. This system allows the computation of topographical cortical measurements for segmentation data generated from manual and semi-automated volumetric sources other than FreeSurfer. These measurements can be regionally specific and integrated with systems of cortical parcellation that subdivides the neocortex into gyral-based parcellation units (PUs). This system of topographical analysis of the cerebral cortex is consistent with current views of cortical development and neural systems organization of the human and non-human primate brain.

YNIMG Journal 2005 Journal Article

MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability

• Nikos Makris
• John E. Schlerf
• Steven M. Hodge
• Christian Haselgrove
• Matthew D. Albaugh
• Larry J. Seidman
• Scott L. Rauch
• Gordon Harris

We revisit here a surface assisted parcellation (SAP) system of the human cerebellar cortex originally described in Makris, N. , Hodge, S. M. , Haselgrove, C. , Kennedy, D. N. , Dale, A. , Fischl, B. , Rosen, B. R. , Harris, G. , Caviness, V. S. , Jr. , Schmahmann, J. D. , 2003. Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging. J Cogn Neurosci 15, 584–599. This system preserves the topographic and morphologic uniqueness of the individual cerebellum and allows for volumetric analysis and representation of multimodal structural and functional data on the cerebellar cortex. This methodology integrates features of automated routines of the program FreeSurfer as well as semi-automated and manual procedures of the program Cardviews to create 64 cerebellar parcellation units based on fissure information and anatomical landmarks of the cerebellar surface. Using this technique, we undertook the parcellation of ten cerebella by two independent raters. The reliability of the resulting parcellation units (64 total) was high, with an average Intraclass Correlation Coefficient (ICC) of 0. 724 in the vermis and 0. 853 in the hemispheres. Clusters of parcellation units were then created, based on lobar and connectivity data and functional hypotheses. These 36 clusters, when treated as anatomical units, had an average ICC of 0. 933. Whereas the individual units provide a high level of detail and anatomical specificity, the clusters add flexibility to the analysis by providing higher reliability.

YNIMG Journal 1998 Journal Article

Anterior Cingulate (Cognitive Division) Fails to Show fMRI Activation in Adults with Attention Deficit Disorder During the Counting Stroop Task

• George Bush
• Jean A. Frazier
• Paul J. Whalen
• Larry J. Seidman
• Joseph Biederman
• Bruce R. Rosen
• Scott L. Rauch