title: Disruption of anterior insula modulation of large-scale brain networks in schizophrenia.
abstract: BACKGROUND
  Systems level modeling of functional magnetic resonance imaging data has demonstrated dysfunction of several large-scale brain networks in schizophrenia. Anomalies across multiple functional networks associated with schizophrenia could be due to diffuse pathology across multiple networks or, alternatively, dysfunction at converging control(s) common to these networks. The right anterior insula has been shown to modulate activity in the central executive and default mode networks in healthy individuals. We tested the hypothesis that right anterior insula modulation of central executive and default mode networks is disrupted in schizophrenia and associated with cognitive deficits.
  
  
  METHODS
  In 44 patients with schizophrenia and 44 healthy control subjects, we used seed-based resting state functional connectivity functional magnetic resonance imaging analysis to examine connectivity between right insular subregions and central executive/default mode network regions. We also performed two directed connectivity analyses of resting state data: Granger analysis and confirmatory structural equation modeling. Between-group differences in path coefficients were used to evaluate anterior insula modulation of central executive and default mode networks. Cognitive performance was assessed with the rapid visual information processing task, a test of sustained attention.
  
  
  RESULTS
  With multiple connectivity techniques, we found compelling, corroborative evidence of disruption of right anterior insula modulation of central executive and default mode networks in patients with schizophrenia. The strength of right anterior insula modulation of these networks predicted cognitive performance.
  
  
  CONCLUSIONS
  Individuals with schizophrenia have impaired right anterior insula modulation of large-scale brain networks. The right anterior insula might be an emergent pathophysiological gateway in schizophrenia.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA. lmoran@mprc.umaryland.edu
authors.forename: Lauren V
authors.initials: LV
authors.lastname: Moran
authors.forename: Malle A
authors.initials: MA
authors.lastname: Tagamets
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Sampath
authors.forename: Alan
authors.initials: A
authors.lastname: O'Donnell
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D012559:Schizophrenia / Q000503:physiopathology*
keywords: Anterior insula; central executive network; default mode network; imaging; salience network; schizophrenia