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General and Specific Functional Connectivity Disturbances in First-Episode Schizophrenia During Cognitive Control Performance

  • Alex Fornito
    Correspondence
    Address correspondence to Alex Fornito, Ph.D., Melbourne Neuropsychiatry Centre, University of Melbourne; Levels 1 and 2, 161 Barry Street, Carlton South, Victoria 3053, Australia
    Affiliations
    Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom

    Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Australia
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  • Jong Yoon
    Affiliations
    Translational Cognitive and Affective Neuroscience Laboratory, University of California, Davis, California
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  • Andrew Zalesky
    Affiliations
    Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, Australia
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  • Edward T. Bullmore
    Affiliations
    Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom

    GlaxoSmithKline Clinical Unit Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
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  • Cameron S. Carter
    Affiliations
    Translational Cognitive and Affective Neuroscience Laboratory, University of California, Davis, California
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      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.

      Key Words

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