Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI

Background: Neuroimaging studies of schizophrenic subjects performing worki ng memory (WM) tasks have demonstrated a relative hypoactivity of prefronta l cortex compared,with normal subjects. Methods: Using functional magnetic resonance imaging (fMRI), we compared do rsolateral prefrontal cortex (DLPFC) activation in 12 schizophrenic and 10 normal subjects during rewarded performance of a WM task. Subjects performe d a modified version of the Sternberg Item Recognition Paradigm (SIRP), a c ontinuous performance, choice reaction time (RT) task that requires WM. We compared a high WM load condition with a nonWM choice RT condition and with a low WM load condition. Results: Schizophrenic subjects performed the tasks better than chance but worse than normal subjects. They showed greater activation than normal subj ects in the left DLPFC but did not differ in the right DLPFC or in the cont rol region. In the schizophrenic group, left DLPFC activation was inversely correlated with task performance, as measured by errors. Conclusions: These findings contrast with previous studies that demonstrate d task-related hypofrontality in schizophrenia. Task parameters that may co ntribute to this difference are discussed. We hypothesize that the performa nce and activation differences we observed are also manifestations of prefr ontal dysfunction in schizophrenia. They reflect inefficient functioning of the neural circuitry involved in WM. (C) 1999 Society of Biological Psychi atry.