This is an application for competing continuation of the Independent Scientist Award (K02), The Natural History of Dementia. The goals of the original award period included learning the theories, skills and methodologies necessary to analyze the results of longitudinal studies of progressive dementia. However, functional neuroimaging has played an increasingly important role in the applicant's developing research career. One strength of functional imaging lies in the ability to examine the breakdowns in the functional connectivity of cognitive brain systems, and how these breakdowns relate to cognitive function. The statistical techniques needed to accomplish these goals are new, and difficult to implement. Therefore, the purpose of this ISA is to free the applicant from administrative and clinical responsibilities to focus his attention on acquiring the theories and methodologies of higher- level statistical analysis of functional neuroimaging data. The research plan concerns the changes in cognition associated with advancing HIV infection and AIDS. Using HIV plus subjects recruited through a community-based sentinel network of primary care providers, we will track the neuropsychological, neurological, and psychosocial characteristics of subjects over a three year follow-up period. At study entry, and then at specific times during follow-up, subjects will complete structural and functional magnetic resonance imaging (MRI) scans; these data are the basis of the career development plan. The applicant will learn the techniques of measuring brain structure and function, and how to relate these to behavioral outcomes. Collaboration and structured laboratory visits with scientists at three research facilities will permit the applicant to learn and develop procedures such as structural equation modeling. The applicant will learn the skills needed to dissect the functional connectivity of brain systems in HIV/AIDS patients. These studies will provide critical information with regard to the breakdown in the integrity of cognitive processes in HIV- infected individuals. The ISA will permit the applicant to acquire state-of-the-art analytical strategies that will significantly enhance his continued career development.
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