Organization of Cognitive Control Within the Lateral Prefrontal Cortex in Schizophrenia

Context: Cognitive control is highly affected in schizophrenia, but its overall functional architecture remains poorly understood. A recent study demonstrated that, in healthy subjects, cognitive control is functionally organized within the lateral prefrontal cortex (LPFC) as a cascade of representations ranging from premotor to anterior LPFC regions according to stimuli, the present perceptual context, and the temporal episode in which stimuli occur. Objective: To determine the functional hierarchical organization of cognitive control within the LPFC in patients with schizophrenia. Design: Case-control study. Setting: Hospital-based research units. Participants: Fifteen schizophrenic patients and 14 controls. Main Outcome Measures: Behavioral performance and regional brain activity as measured by functional magnetic resonance imaging during a task, varying the amount of information conveyed by episodic and contextual signals. Results: In patients and healthy controls, activity in caudal LPFC regions varied as episodic and contextual signals, whereas rostral LPFC regions only exhibited an episodic effect. However, patients made more errors than controls when information conveyed by contextual and episodic signals increased. These impairments were related to hypoactivation in caudal LPFC regions and hyperactivation in rostral LPFC regions, respectively. Activation in caudal LPFC regions negatively correlated with the disorganization syndrome score of patients. Conclusions: In schizophrenic patients, the architecture of cognitive control follows the cascading organization from rostral LPFC regions to caudal LPFC and premotor regions depending on the temporal framing of action and events. We found, however, that immediate contextual signals insufficiently bias the caudal LPFC activity required to select the appropriate behavioral representation. This specific deficit could thus alter the internal consistency of schizophrenic patients' behavior. To compensate for this weakening of contextual influence, schizophrenic patients may inefficiently use temporal episodic information through higher activation in rostral LPFC regions.