title: Connectomic disturbances in attention-deficit/hyperactivity disorder: a whole-brain tractography analysis.
abstract: BACKGROUND
  Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD.
  
  
  METHODS
  Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD.
  
  
  RESULTS
  A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p < .05, family-wise error-corrected). Moreover, fractional anisotropy in some of these fiber bundles correlated with attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p < .05, family-wise error-corrected) predominantly linking frontal, cingulate, and supplementary motor areas. Fractional anisotropy in this network was also correlated with continuous performance test scores.
  
  
  CONCLUSIONS
  Using an unbiased, whole-brain, data-driven approach, we demonstrated abnormal white matter connectivity in ADHD. The correlations observed with measures of attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD.
authors: Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia; Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Soon-Beom
authors: SB
authors: Hong
authors: Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health.
authors: Andrew
authors: A
authors: Zalesky
authors: Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health; Monash Clinical and Imaging Neuroscience, School of Psychology and Psychiatry & Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.
authors: Alex
authors: A
authors: Fornito
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Subin
authors: S
authors: Park
authors: Department of Psychiatry, Pusan National University Yangsan Hospital, Yangsan.
authors: Young-Hui
authors: YH
authors: Yang
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Min-Hyeon
authors: MH
authors: Park
authors: Department of Radiology, Seoul National University Hospital.
authors: In-Chan
authors: IC
authors: Song
authors: Department of Radiology, Seoul National University Hospital.
authors: Chul-Ho
authors: CH
authors: Sohn
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Min-Sup
authors: MS
authors: Shin
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Bung-Nyun
authors: BN
authors: Kim
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors: Soo-Churl
authors: SC
authors: Cho
authors: Department of Psychiatry, Chung Ang University, College of Medicine.
authors: Doug Hyun
authors: DH
authors: Han
authors: Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea.
authors: Jae Hoon
authors: JH
authors: Cheong
authors: Division of Child and Adolescent Psychiatry, Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Republic of Korea. Electronic address: adore412@paran.com.
authors: Jae-Won
authors: JW
authors: Kim
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002648:Child; D063132:Connectome; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000473:pathology*
keywords: ADHD; connectomics; diffusion tensor imaging; network; tractography; white matter