This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of the proposed study is to visualize which regions of the brain show different metabolic activity in schizotypal patients and schizophrenic patients compared to normal controls while they are engaged in a carefully defined visual-spatial working memory task. This will help us to better understand the neurobiological mechanisms of cognitive impairment in schizophrenia. Schizotypal patients are a particularly informative group to study to understand the cognitive impairments in schizophrenia since they share genetic and phenomenological features with schizophrenia, yet do not have concurrent psychotic symptoms which might confound interpretation of the regional brain metabolic activity associated with cognitive impairment. SPD patients also typically provide a population that has not been exposed to neuroleptic medications, the chronic effects of which, could introduce an artifact in studies of brain activity. The proposed study will use fMRI to record regional cerebral blood flow (rCBF), a measure of cerebral metabolic activity, in 24 SPD patients 24 schizophrenic patients and 48 normal controls as they carry out a visual-spatial working memory task. Hypothesis: We expect that schizophrenia spectrum patients (SPD and SCZ patents) will have a functional impairment in BA 9/46 and will activate this region less strongly than healthy controls in carrying out a visuospatial working memory task. To compensate, they will recruit other cortical areas, including BA 10, in particular. However, SCZ patients may not be able to activate BA 10 as effectively as SPD patients, likely because of a greater degree of pathology in the frontal lobe.
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