Prefrontal cortical dysfunction during visual perspective-taking in schizophrenia.

Schizophrenia is characterized by marked impairments in a broad and diverse array of social-cognitive domains. Fundamental deficits in the ability to visualize and shift to the perspectives of others and the neural networks that support this ability may contribute to many of these impairments. This study sought to investigate deficits in prefrontal brain function and connectivity in patients with schizophrenia during visual perspective-taking, and the degree to which such deficits contribute to higher-order impairments in social cognition. A total of 20 outpatients with schizophrenia and 20 age- and gender-matched healthy volunteers completed a basic, visual perspective-taking task during functional magnetic resonance imaging, along with a behavioral assessment of theory of mind after neuroimaging. Results revealed hypoactivity in the medial prefrontal (anterior cingulate) and orbitofrontal cortices during perspective-taking trials compared to control trials in schizophrenia patients relative to healthy controls. In addition, patients demonstrated significant deficits in negative connectivity between medial prefrontal and medial-temporal regions during perspective-taking, which fully mediated behavioral impairments observed in theory of mind. These findings suggest that disruptions are present in the most fundamental aspects of perspective-taking in schizophrenia, and that these disruptions impact higher-order social information processing.