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

ABSTRACT: 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.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.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.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.

SUBMITTER: Fornito A

PROVIDER: S-EPMC4015465 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Fornito Alex A Yoon Jong J Zalesky Andrew A Bullmore Edward T ET Carter Cameron S CS

Biological psychiatry 20110422 1

<h4>Background</h4>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 contr ...[more]

PMID: 21514570

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Project description:Previous evidence has implicated corticostriatal abnormalities in the pathophysiology of psychosis. Although the striatum is the primary target of all efficacious antipsychotics, the relationship between its functional connectivity and symptomatic reduction remains unknown.To explore the longitudinal effect of treatment with second-generation antipsychotics on functional connectivity of the striatum during the resting state in patients experiencing a first episode of psychosis.This prospective controlled study took place at a clinical research center and included 24 patients with first-episode psychosis and 24 healthy participants matched for age, sex, education, and handedness. Medications were administered in a double-blind randomized manner.Patients were scanned at baseline and after 12 weeks of treatment with either risperidone or aripiprazole. Their symptoms were evaluated with the Brief Psychiatric Rating Scale at baseline and follow-up. Healthy participants were scanned twice within a 12-week interval.Functional connectivity of striatal regions was examined via functional magnetic resonance imaging using a seed-based approach. Changes in functional connectivity of these seeds were compared with reductions in ratings of psychotic symptoms.Patients had a median exposure of 1 day to antipsychotic medication prior to being scanned (mean [SD]?= 4.5 [6.1]). Eleven patients were treated with aripiprazole and 13 patients were treated with risperidone. As psychosis improved, we observed an increase in functional connectivity between striatal seed regions and the anterior cingulate, dorsolateral prefrontal cortex, and limbic regions such as the hippocampus and anterior insula (P <?.05, corrected for multiple comparisons). Conversely, a negative relationship was observed between reduction in psychosis and functional connectivity of striatal regions with structures within the parietal lobe (P <?.05, corrected for multiple comparisons).Our results indicated that corticostriatal functional dysconnectivity in psychosis is a state-dependent phenomenon. Increased functional connectivity of the striatum with prefrontal and limbic regions may be a biomarker for improvement in symptoms associated with antipsychotic treatment.

Dataset Information

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

Publications

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

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