The goal of the proposed research is to use functional magnetic resonance imaging (fMRI) to test two primary hypotheses about the nature of memory impairments in schizophrenia. The first is that impaired episodic memory in schizophrenia is related to dysfunctional semantic processing, reflected in failure to activate left inferior frontal gyrus (LIFG) during word encoding and recognition. The second hypothesis is that this LIFG dysfunction is primarily due to patients' impaired controlled processing of semantic information, rather than degradation of their semantic memory knowledge or automatic associative processes. The first hypothesis will be tested in experiments 1 & 2. Experiment one will employ the Penn Word Recognition Test (PWRT) which will allow us to replicate previous Positron Emission Tomography findings that impaired episodic memory is related to LIFG dysfunction during word encoding and retrieval. Experiment 2 will employ a shallow/deep word encoding and recognition paradigm that will permit us to test the role of self-generated organizational strategies in the semantic processing difficulties and related LIFG dysfunction in schizophrenia. The second primary hypothesis will be tested in the final two experiments. Experiment 3 will employ a cued semantic verbal fluency paradigm that will allow us to investigate the effect of reducing controlled processing demands on verbal fluency and LIFG function. The final experiment will use an uncued verbal fluency design that will permit a trial-by-trial examination of the effect of controlled versus automatic processing on LIFG function. This series of studies promises to uncover fundamental mechanisms of impaired semantic processing and related episodic memory and LIFG deficits in schizophrenia. Establishing this mechanism will lay the groundwork for future imaging studies and can help provide a rationale for developing cognitive interventions designed to remediate semantic processing and verbal memory deficits in schizophrenia in order to improve functional outcome.
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