Prefrontal function in schizophrenia: confounds and controversies

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
D R Weinberger, K F Berman

Abstract

A wealth of clinical data indirectly implicate dysfunction of frontal cortex in schizophrenia, including negative symptoms, the pattern of neuropsychological deficits, and abnormal eye movements. Neuroimaging studies have provided direct evidence of frontal, particularly prefrontal, malfunction, but the results have been inconsistent and controversial. The burning question is whether prefrontal hypofunction is a pathophysiological characteristic of schizophrenia per se or an artifact of the imaging protocol. In studies of patients at rest, 'hypofrontality' has been an inconsistent finding, probably because resting is physiologically and psychologically variable. Cognitive activation paradigms, especially during working memory tasks, have been reliable in showing prefrontal hypofunction in patients, but these results have been challenged as artifacts of poor performance. Performance differences have been addressed by studying patients and controls matched either for poor performance or for normal performance. The former approach, which has the potential of elucidating the specificity of physiological mechanisms associated with poor performance, has shown that prefrontal activity in patients with schizophrenia differs quantitativ...Continue Reading

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