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Acquiring and Inhibiting Prepotent Responses in Schizophrenia
Event-Related Brain Potentials and Functional Magnetic Resonance Imaging
Judith M. Ford, PhD;
Max Gray, BA;
Susan L. Whitfield, MA;
And U. Turken, PhD;
Gary Glover, PhD;
William O. Faustman, PhD;
Daniel H. Mathalon, PhD, MD
Arch Gen Psychiatry. 2004;61:119-129.
Background Schizophrenia is associated with deficits in using context to establish prepotent responses in complex paradigms and failures to inhibit prepotent responses once established.
Objective To assess prepotent response establishment and inhibition in patients with schizophrenia using event-related brain potential (ERP) and functional magnetic resonance imaging (fMRI) in a simple NoGo task. To combine fMRI and ERP data to focus on fMRI activations associated with the brief (approximately 200 ms) moment of context updating reflected in the NoGo P300 ERP component.
Design and Setting We collected ERP and fMRI data while subjects performed a NoGo task requiring a speedy button press to X stimuli (P = .88) but not to K stimuli (P = .12). The ERPs were collected at the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif; fMRIs were collected at Stanford University, Stanford, Calif.
Participants We recruited patients with DSM-IV schizophrenia (n = 11) from the community and the VA hospital and sex- and age-matched healthy control subjects (n = 11) from the community.
Main Outcome Measures Behavioral accuracy, P300 amplitudes and latencies, and fMRI activations suggested that patients with schizophrenia did not establish as strong a prepotent tendency to respond to the Go stimulus as healthy subjects. In healthy subjects, NoGo P300 was related to activations in the anterior cingulate cortex, dorsal lateral prefrontal cortex, and right inferior parietal lobule and caudate nucleus, perhaps reflecting conflict experienced when withholding a response, control needed to inhibit a response, and stopping a response in action, respectively. In patients with schizophrenia, NoGo P300 was modestly related to activations in the anterior cingulate cortex, which is consistent with experiencing conflict.
Conclusions The difference in ERP and fMRI responses to Go and NoGo stimuli suggested that inhibiting a response was easier for patients with schizophrenia than for healthy subjects. Correlations of P300 and fMRI data suggested that patients with schizophrenia and healthy subjects used different neural structures to inhibit responses, with healthy subjects using a more complex system.
From the Departments of Psychiatry and Behavioral Sciences (Drs Ford, Turken and Faustman and Mr Gray and Ms Whitfield) and Radiology (Dr Glover), Stanford University School of Medicine, Stanford, Calif; Psychiatry Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif (Drs Ford, Turken and Faustman and Mr Gray and Ms Whitfield); the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn (Dr Mathalon); and Psychiatry Service, Veterans Affairs West Haven Health Care System, West Haven, Conn (Dr Mathalon).
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