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Paul C. Fletcher, MRCPsych; Peter J. McKenna, MRCPsych; Christopher D. Frith, PhD; Paul M. Grasby, MRCPsych; Karl J. Friston, MRCPsych; Raymond J. Dolan, MRCPsych

Arch Gen Psychiatry. 1998;55:1001-1008.

Background  Functional neuroimaging experiments have implicated prefrontal cortex (PFC) in memory processes. Several studies of schizophrenic patients have shown failure of activation in the dorsolateral region of PFC (DLPFC). We used a graded memory challenge to characterize functional neuroanatomical differences between schizophrenic and control subjects. The graded manipulation of task demands enabled us to assess group differences in the context of normal and abnormal psychological task performance.

Methods  Memory-related activity was assessed using positron emission tomography in schizophrenic patients and age-matched controls during performance of a graded memory task. Subjects underwent scanning while learning and recalling word lists of variable length.

Results  We used a model that assessed linear and nonlinear effects of memory load. Nonlinear group differences in DLPFC activation were observed. Controls showed a steepening slope of DLPFC increase as task demands increased. By contrast, schizophrenic subjects showed initial DLPFC increases that fell away with increasing memory load. The DLPFC response in schizophrenic subjects was closely related to measured task performance. In addition, schizophrenic subjects failed to show task-related decreases in activity in the left superior temporal and inferior parietal gyrus.

Conclusions  Patients with schizophrenia showed a failure in DLPFC activation only in the face of diminished performance measures, suggesting that a full characterization of task-related changes in DLPFC activation must consider performance levels. However, striking failures of deactivation in superior temporal and inferior parietal regions were independent of task performance, possibly reflecting a core abnormality of the condition.

From the Wellcome Department of Cognitive Neurology, Institute of Neurology, London (Drs Fletcher, Frith, and Friston), the Department of Psychological Medicine, Fulboum Hospital, Cambridge (Dr McKenna), the Medical Research Council Cyclotron Unit, Hammersmith Hospital, London (Dr Grasby), and the Department of Psychological Medicine, Royal Free Hospital Medical School, London (Dr Dolan), England.

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