Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia

Background: Previously we proposed that dorsolateral prefrontal cortex (PFC ) supports a specific working memory (WM) subcomponent: the ability to repr esent and maintain context information necessary to guide appropriate task behavior. By context, we mean prior task-relevant information represented i n such a form that it supports selection of the appropriate behavioral resp onse. Furthermore, we hypothesized that WM deficits in schizophrenia reflec t impaired context processing due to a disturbance in dorsolateral PFC. We use functional magnetic resonance imaging to examine PFC activation in medi cation-naive, first-episode patients with schizophrenia during a WM, task-i solating context processing. Methods: Fourteen first-episode, medication-naive patients with schizophren ia and 12 controls similar in age, sex, and parental education underwent fu nctional magnetic resonance imaging during performance of an A-X version of the Continuous Performance Test. Results: Patients with schizophrenia demonstrated deficits in dorsolateral PFC activation in task conditions requiring context processing but showed i ntact activation of posterior and inferior PFC. In addition, patients demon strated intact activation of the primary motor and somatosensory cortex in response to stimulus processing demands. Conclusions: These results demonstrate selectivity in dorsolateral PFC dysf unction among medication-naive first-episode patients with schizophrenia, s uggesting that a specific deficit in PFC function is present at illness ons et, prior to the administration of medication or the most confounding effec ts of illness duration. Furthermore, these results are consistent with the hypothesis that WM deficits in patients with schizophrenia reflect an impai rment in context processing due to a disturbance in dorsolateral PFC functi on.