title: Impaired insight into illness and cognitive insight in schizophrenia spectrum disorders: resting state functional connectivity.
abstract: BACKGROUND
  Impaired insight into illness (clinical insight) in schizophrenia has negative effects on treatment adherence and clinical outcomes. Schizophrenia is described as a disorder of disrupted brain connectivity. In line with this concept, resting state networks (RSNs) appear differentially affected in persons with schizophrenia. Therefore, impaired clinical, or the related construct of cognitive insight (which posits that impaired clinical insight is a function of metacognitive deficits), may reflect alterations in RSN functional connectivity (fc). Based on our previous research, which showed that impaired insight into illness was associated with increased left hemisphere volume relative to right, we hypothesized that impaired clinical insight would be associated with increased connectivity in the DMN with specific left hemisphere brain regions.
  
  
  METHODS
  Resting state MRI scans were acquired for participants with schizophrenia or schizoaffective disorder (n=20). Seed-to-voxel and ROI-to-ROI fc analyses were performed using the CONN-fMRI fc toolbox v13 for established RSNs. Clinical and cognitive insight were measured with the Schedule for the Assessment of Insight-Expanded Version and Beck Cognitive Insight Scale, respectively, and included as the regressors in fc analyses.
  
  
  RESULTS
  As hypothesized, impaired clinical insight was associated with increased connectivity in the default mode network (DMN) with the left angular gyrus, and also in the self-referential network (SRN) with the left insula. Cognitive insight was associated with increased connectivity in the dorsal attention network (DAN) with the right inferior frontal cortex (IFC) and left anterior cingulate cortex (ACC).
  
  
  CONCLUSIONS
  Increased connectivity in DMN and SRN with the left angular gyrus and insula, respectively, may represent neural correlates of impaired clinical insight in schizophrenia spectrum disorders, and is consistent with the literature attributing impaired insight to left hemisphere dominance. Increased connectivity in the DAN with the IFC and ACC in relation to cognitive insight may facilitate enhanced mental flexibility in this sample.
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada; Geriatric Mental Health Program, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of British Columbia, Canada.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Menon
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of Toronto, Canada; Department of Psychiatry, Faculties of Medicine and Health Science, University of Malta, Msida, Malta.
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.affiliation: Schizophrenia Program, Centre for Addiction & Mental Health, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: Schizophrenia Program, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction & Mental Health, Canada; Geriatric Mental Health Program, Centre for Addiction & Mental Health, Canada; Department of Psychiatry, University of Toronto, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction & Mental Health, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: Ariel.Graff@camh.ca.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000377:Agnosia / Q000503:physiopathology; D001364:Awareness / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D011618:Psychotic Disorders / Q000503:physiopathology* / Q000523:psychology*; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D055815:Young Adult
keywords: Anosognosia; Cognitive insight; Default mode network; Functional MRI; Illness awareness; Insight; Resting state networks