FUNCTIONAL HYPOFRONTALITY AND WORKING-MEMORY DYSFUNCTION IN SCHIZOPHRENIA

Objective: Hypofrontality is a common but not invariable finding in sc hizophrenia. Inconsistencies in the literature may reflect, in part, t he fact that abnormal physiological responses in the prefrontal cortex are best identified under conditions that place well-specified functi onal demands on this region. Method: The authors studied eight patient s with schizophrenia and eight matched comparison subjects using [O-15 ]H2O positron emission tomography and the ''N-back'' task, which activ ates the prefrontal cortex as a function of working memory load in nor mal subjects. Results: Under low-working-memory-load conditions, the a ccuracy of both groups in the N-back task was equal, but when the memo ry load increased, the patients' performance deteriorated more than di d that of the comparison subjects. The regional cerebral blood flow re sponse to increased working memory load was significantly reduced in t he patients' right dorsolateral prefrontal cortex. Conclusions: These results confirm the importance of using tasks that tap specific cognit ive functions, linked to specific neural systems, in studies of brain- behavior relationships in schizophrenia. Hypofrontality is reliably de monstrated in schizophrenia during tasks that engage working memory fu nctions of the prefrontal cortex.