The objective of this proposal is to support the candidate's development of skills necessary to perform patient-oriented research in behavioral neuroscience. The training component includes the mentored development of skills in various methods of quantitative MRI analysis, and includes coursework and mentored training in behavioral neurology, advanced biostatistics, neural network modeling, and the scientifically rigorous and responsible conduct of research. These neurologic/medical skills are intended to complement the applicant's previous training in psychological and neuropsychological assessment and research. The proposed research plan will support the candidate's development of these skills by giving her the opportunity to investigate the neuroanatomical and neuropsychological substrates of social behavior with frontotemporal dementia (FTD) patients. Though this disease causes early and often dramatic changes in social functioning along with diverse patterns of brain atrophy in the frontal lobes, temporal lobes, and amygdala, little has been done to either systematically quantify the social changes or to link social features to specific brain areas. Through this proposal, data on social and interpersonal functioning will be collected on 75 FTD patients and 25 healthy controls using neuropsychological tests of social cognition, questionnaires administered to family members, and clinical behavioral observation. These subjects' MRI scans will be made available to the candidate for quantitative analysis using manual and automated region of interest (ROI) and voxel-based morphometry (VBM) analyses. Data from subjects' general neuropsychological evaluations at the UCSF Memory and Aging Center will also made available for analysis in conjunction with the social data. The specific hypotheses are that 1) decreased right anterior temporal lobe volume will correspond with loss of interpersonal warmth and empathic orientation to others, 2) Decreased right dorsolateral prefrontal cortex volume will correspond to distortion of social reasoning and inaccurate interpretation of social situations. It is also hypothesized that 3) variance in empathy, and 4) variance in assertiveness, will be predicted by scores on neuropsychological tests of cognitive functions corresponding to hypothesized cognitive models, and that these models can be validated via analysis in conjunction with morphometry analyses of brain tissue loss.
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