title: Multimodal magnetic resonance imaging study of treatment-naïve adults with attention-deficit/hyperactivity disorder.
abstract: BACKGROUND
  Attention-Deficit/Hiperactivity Disorder (ADHD) is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication.
  
  
  METHODS
  A newly validated method named optimally-discriminative voxel-based analysis (ODVBA) was applied to multimodal (structural and DTI) MRI data acquired from 22 treatment-naïve ADHD adults and 19 age- and gender-matched healthy controls (HC).
  
  
  RESULTS
  Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM) of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity) in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM) in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus.
  
  
  CONCLUSIONS
  Our results suggest that adult ADHD is associated with neuroanatomical abnormalities mainly affecting the WM microstructure in fronto-parieto-temporal circuits that have been implicated in cognitive, emotional and visuomotor processes.
authors.affiliation: Laboratory of Psychiatric Neuroimaging, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, Sao Paulo, São Paulo, Brazil; Program for Attention Deficit Hyperactivity Disorder, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Chaim
authors.affiliation: Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, Unites States of America.
authors.forename: Tianhao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Laboratory of Psychiatric Neuroimaging, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, Sao Paulo, São Paulo, Brazil.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Zanetti
authors.affiliation: Program for Attention Deficit Hyperactivity Disorder, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: da Silva
authors.affiliation: Program for Attention Deficit Hyperactivity Disorder, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil.
authors.forename: Mário R
authors.initials: MR
authors.lastname: Louzã
authors.affiliation: Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, Unites States of America.
authors.forename: Jimit
authors.initials: J
authors.lastname: Doshi
authors.affiliation: Laboratory of Psychiatric Neuroimaging, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, Sao Paulo, São Paulo, Brazil.
authors.forename: Mauricio H
authors.initials: MH
authors.lastname: Serpa
authors.affiliation: Laboratory of Psychiatric Neuroimaging, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, Sao Paulo, São Paulo, Brazil.
authors.forename: Fabio L S
authors.initials: FL
authors.lastname: Duran
authors.affiliation: Laboratory of Psychiatric Neuroimaging, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, Sao Paulo, São Paulo, Brazil.
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Caetano
authors.affiliation: Section of Biomedical Image Analysis, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, Unites States of America.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Laboratory of Psychiatric Neuroimaging, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo, Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences, University of São Paulo, Sao Paulo, São Paulo, Brazil.
authors.forename: Geraldo F
authors.initials: GF
authors.lastname: Busatto
mesh_terms: D000328:Adult; D016880:Anisotropy; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D016022:Case-Control Studies; D015897:Comorbidity; D003710:Demography; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging