title: Failure to mobilize cognitive control for challenging tasks correlates with symptom severity in schizophrenia.
abstract: Deficits in the adaptive, flexible control of behavior contribute to the clinical manifestations of schizophrenia. We used functional MRI and an antisaccade paradigm to examine the neural correlates of cognitive control deficits and their relations to symptom severity. Thirty-three chronic medicated outpatients with schizophrenia and 31 healthy controls performed an antisaccade paradigm. We examined differences in recruitment of the cognitive control network and task performance for Hard (high control) versus Easy (low control) antisaccade trials within and between groups. We focused on the key regions involved in 'top-down' control of ocular motor structures - dorsal anterior cingulate cortex, dorsolateral and ventrolateral prefrontal cortex. In patients, we examined whether difficulty implementing cognitive control correlated with symptom severity. Patients made more errors overall, and had shorter saccadic latencies than controls on correct Hard vs. Easy trials. Unlike controls, patients failed to increase activation in the cognitive control network for Hard vs. Easy trials. Reduced activation for Hard vs. Easy trials predicted higher error rates in both groups and increased symptom severity in schizophrenia. These findings suggest that patients with schizophrenia are impaired in mobilizing cognitive control when presented with challenges and that this contributes to deficits suppressing prepotent but contextually inappropriate responses, to behavior that is stimulus-bound and error-prone rather than flexibly guided by context, and to symptom expression. Therapies aimed at increasing cognitive control may improve both cognitive flexibility and reduce the impact of symptoms.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.
authors.forename: Bengi
authors.initials: B
authors.lastname: Baran
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.
authors.forename: F Işık
authors.initials: FI
authors.lastname: Karahanoğlu
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.
authors.forename: Yigal
authors.initials: Y
authors.lastname: Agam
authors.affiliation: Psychiatry Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Mantonakis
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States.
authors.forename: Dara S
authors.initials: DS
authors.lastname: Manoach
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology*; D012438:Saccades / Q000502:physiology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000503:physiopathology*
keywords: Anterior cingulate cortex; Antisaccade; Cognitive control; Functional MRI; Prefrontal cortex; Schizophrenia