Diverse evidence suggests that deficits in working memory and long-term memory in patients with schizophrenia reflect deficits in at least two putatively distinct cognitive domains. Furthermore, deficits in working memory have typically been linked to an underlying disturbance in prefrontal cortex function, while deficits in long-term memory (i.e., encoding and/or retrieval) have typically been associated with medial temporal/hippocampal deficits. The investigator proposes to test an alternative hypothesis that deficits in both working memory and long-term memory in patients with schizophrenia reflect a single underlying disturbance in prefrontal cortex function. This hypothesis would be tested by a neuroactivation analysis of cognitive tasks using functional magnetic resonance imaging (fMRI) techniques and an event-related neuroimaging design. The investigator proposes to define the distributed patterns of cortical function and dysfunction associated with the performance of both working memory and long-term memory tasks during the same imaging session and the same patients with schizophrenia and in matched normal comparison subjects. This design is novel in that it represents the first functional neuroimaging study in schizophrenia attempting to simultaneously assess multiple cognitive domains and thus could impact strongly the current understanding of the precise nature and mechanisms underlying cognitive impairments associated with schizophrenia. A related specific aim of the proposal would compare the task-related lateralized brain activation for working memory and long-term memory tasks using verbal versus non-verbal (non-nameable faces) stimuli in patients with schizophrenia and healthy comparison subjects. Cognitive impairments are increasingly recognized as core features of schizophrenia. Demonstrating that deficits in both working memory and long-term memory in schizophrenia stem from a single underlying disturbance in prefrontal cortex function would both simplify and clarify the conceptualization of cognitive dysfunction in schizophrenia. These studies could also provide the groundwork for the development of powerful new behavioral, as well as neuroimaging, probes of cognitive and neurobiological function in schizophrenia.
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