Recent utilization of variable performance tasks have contributed to a solution here.69 rCBF studies in schizophrenia have been used to identify CNS regions of abnormal function in the illness. While no single region #BEZ235 randurls[1|1|,|CHEM1|]# has

been identified in all laboratories, several distinct abnormalities are prominent and suggest, above all, the possibility that an abnormality of several systems in the brain underlies the illness. Initially, the middle frontal cortex (dorsolateral prefrontal region) was identified as abnormal in schizophrenia66 and has subsequently been tied to manifestations of primary negative symptoms in the illness.8,64,71 More recently, laboratories have focused on the anterior cingulate Inhibitors,research,lifescience,medical cortex (ACQ8,73,74 and the hippocampus75 as being potentially primarily involved in the psychotic process. A role of the basal ganglia cannot

be ruled out.76 Functional magnetic resonance imaging (fMRI) studies of rCBF have produced a variety Inhibitors,research,lifescience,medical of results, often with conflicting data, possibly because of the augmented Inhibitors,research,lifescience,medical spatial resolution of this methodology. For example, during studies involving performance of a motor task in three different laboratories, subjects with schizophrenia were found to show no differences from normal subjects in rCBF,77,78 or increased rCBF,79 or decreased rCBF80 in the sensorimotor cortex. Each of these studies suggested the potential of an interactive effect with previous or current antipsychotic medication. Tasks demanding higher-order cognitive Inhibitors,research,lifescience,medical functions, such as attention or working memory, have also resulted in conflicting data. For example, one study found an increase in frontal cortical rCBF in schizophrenia compared with healthy persons with a working memory task, whereas two other laboratories reported decreases in this area with a similar task. Additional studies in this area will hopefully define the subject variables, performance demands, or the illness phase contribution(s) that are important for an explanation of these discrepancies. Inhibitors,research,lifescience,medical Use of fMRI is rapidly increasing in all academic centers, and so progress

will not lag in this area. The functional imaging studies from our laboratory have compared persons with schizophrenia with matched healthy individuals while performing an auditory recognition Non-specific serine/threonine protein kinase task in an overlearncd, practiced condition, with normals with a similar task performance. The two groups of volunteers performed similarly on accuracy and tone interval. In this situation, the volunteers with schizophrenia showed rCBF differences from the normals only in the ACC/medial frontal cortex. Those schizophrenic volunteers who had a similar performance to normal subjects on the basis of accuracy, but required wide tone disparities to do so, had not only rCBF reductions in the ACC, but. also flow reductions in the middle frontal and inferior frontal cortex (Figure 2).