Mapping the MTL Memory System in Schizophrenia

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DESCRIPTION (provided by applicant): This career development plan will support the candidate's goals of mastering new imaging methodologies to investigate multiple aspects of a specific brain system in schizophrenia. This systems approach will allow a deeper understanding of the mechanisms associated with declarative memory (DM) impairments that are mediated by the medial temporal lobe (MTL) memory system (hippocampus, parahippocampal region and cerebral cortex). Guidance from accomplished investigators, state-of-the-art imaging facilities, and didactic training provide the infrastructure needed to achieve these goals. The rich institutional environment at UCLA further supports the candidate's long-term plan to develop a productive and independent program of research using imaging methods to better understand the pathophysiological underpinnings of brain disturbances in neuropsychiatric disorders. DM impairments and hippocampal volume reductions are shown particularly vulnerable to disease processes in schizophrenia and to indicate a genetic predisposition towards the illness. However, it is uncertain whether abnormalities of declarative memory (DM) reflect disturbances in regional brain activity and/or in functional connectivity and whether such impairments relate to structural abnormalities within this neural network. To address these questions, the candidate will combine structural, functional and diffusion tensor imaging to map structural and functional abnormalities of the MTL memory system in schizophrenia patients, first-degree relatives of patients and healthy comparison subjects recruited through a larger NIMH study, "Transmission of Vulnerability Factors for Schizophrenia." The research plan includes advanced structural image analysis techniques and functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) strategies that will be employed to dissociate the structural and functional correlates of MTL disturbances including declarative memory deficits in schizophrenia and to establish the presence of genetic liability effects.