title: Disrupted prefrontal interhemispheric structural coupling in schizophrenia related to working memory performance.
abstract: BACKGROUND
  Prominent regional cortical thickness reductions have been shown in schizophrenia. In contrast, little is known regarding alterations of structural coupling between regions in schizophrenia and how these alterations may be related to cognitive impairments in this disorder.
  
  
  METHODS
  T1-weighted magnetic resonance images were acquired in 54 patients with schizophrenia and 68 healthy control subjects aged 18-55 years. Cortical thickness was compared between groups using a vertex-wise approach. To assess structural coupling, seeds were selected within regions of reduced thickness, and brain-wide cortical thickness correlations were compared between groups. The relationships between identified patterns of circuit structure disruption and cognitive task performance were then explored.
  
  
  RESULTS
  Prominent cortical thickness reductions were found in patients compared with controls at a 5% false discovery rate in a predominantly frontal and temporal pattern. Correlations of the left dorsolateral prefrontal cortex (DLPFC) with right prefrontal regions were significantly different in patients and controls. The difference remained significant in a subset of 20 first-episode patients. Participants with stronger frontal interhemispheric thickness correlations had poorer working memory performance.
  
  
  CONCLUSIONS
  We identified structural impairment in a left-right DLPFC circuit in patients with schizophrenia independent of illness stage or medication exposure. The relationship between left-right DLPFC thickness correlations and working memory performance implicates prefrontal interhemispheric circuit impairment as a vulnerability pathway for poor working memory performance. Our findings could guide the development of novel therapeutic interventions aimed at improving working memory performance in patients with schizophrenia.
authors.affiliation: Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada;
authors.forename: Anne L
authors.initials: AL
authors.lastname: Wheeler
authors.affiliation: Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada;
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Program in Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada;
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada;
authors.forename: Jon
authors.initials: J
authors.lastname: Pipitone
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, ON, Canada;
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada;
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada;
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Kimel Family Translational Imaging Genetics Laboratory, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; aristotle.voineskos@camh.ca.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009929:Organ Size; D017397:Prefrontal Cortex / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000473:pathology*; D055815:Young Adult
keywords: MRI; cortical thickness; dorsolateral prefrontal cortex; structural coupling