General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance

Alex Fornito, Jong Yoon, Andrew Zalesky, Edward T. Bullmore, Cameron S Carter

Research output: Contribution to journalArticlepeer-review

201 Scopus citations


Background: Cognitive control impairments in schizophrenia are thought to arise from dysfunction of interconnected networks of brain regions, but interrogating the functional dynamics of large-scale brain networks during cognitive task performance has proved difficult. We used functional magnetic resonance imaging to generate event-related whole-brain functional connectivity networks in participants with first-episode schizophrenia and healthy control subjects performing a cognitive control task. Methods: Functional connectivity during cognitive control performance was assessed between each pair of 78 brain regions in 23 patients and 25 control subjects. Network properties examined were region-wise connectivity, edge-wise connectivity, global path length, clustering, small-worldness, global efficiency, and local efficiency. Results: Patients showed widespread functional connectivity deficits in a large-scale network of brain regions, which primarily affected connectivity between frontal cortex and posterior regions and occurred irrespective of task context. A more circumscribed and task-specific connectivity impairment in frontoparietal systems related to cognitive control was also apparent. Global properties of network topology in patients were relatively intact. Conclusions: The first episode of schizophrenia is associated with a generalized connectivity impairment affecting most brain regions but that is particularly pronounced for frontal cortex. Superimposed on this generalized deficit, patients show more specific cognitive-control-related functional connectivity reductions in frontoparietal regions. These connectivity deficits occur in the context of relatively preserved global network organization.

Original languageEnglish (US)
Pages (from-to)64-72
Number of pages9
JournalBiological Psychiatry
Issue number1
StatePublished - Jul 1 2011


  • Complex
  • executive function
  • fMRI
  • graph
  • psychosis
  • small world

ASJC Scopus subject areas

  • Biological Psychiatry


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