PREFRONTAL FUNCTION IN SCHIZOPHRENIA - CONFOUNDS AND CONTROVERSIES

A wealth of clinical data indirectly implicate dysfunction of frontal cortex in schizophrenia, including negative symptoms, the pattern of n europsychological deficits, and abnormal eye movements. Neuroimaging s tudies have provided direct evidence of frontal, particularly prefront al, malfunction, but the results have been inconsistent and controvers ial. The burning question is whether prefrontal hypofunction is a path ophysiological characteristic of schizophrenia per se or an artifact o f the imaging protocol. In studies of patients at rest, 'hypofrontalit y' has been an inconsistent finding, probably because resting is physi ologically and psychologically variable. Cognitive activation paradigm s, especially during working memory tasks, have been reliable in showi ng prefrontal hypofunction in patients, but these results have been ch allenged as artifacts of poor performance. Performance differences hav e 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 mec hanisms associated with poor performance, has shown that prefrontal ac tivity in patients with schizophrenia differs quantitatively and quali tatively from that of normals and of other patient populations who per form at a comparable level. The latter approach, which tends not to fi nd prefrontal differences between patients and controls, may be select ing out important aspects of the disease by focusing on unaffected neu ral functions. While there are pitfalls to each approach and no single study can address all the potential phenomenological confounds, overa ll, the functional neuroimaging database in patients with schizophreni a suggests that prefrontal cognitive deficits are because of prefronta l pathophysiology and not the inverse.