This is a request for an K-23 NIA Mentored Patient Oriented Research Career Award for Darren R Gitelman, MD under the mentorship of M-Marsel Mesulam, MD, Professor of Neurology and Psychiatry at Northwestern University. An important goal of behavioral aging research has been the investigation of age-related changes in Cognitive abilities. However, not all cognitive functions are equally affected by the aging process. """"""""Fluid"""""""" cognitive functions which represent the acquisition of new concepts and adaptation to new situations show the most decline with aging. In contrast, """"""""crystallized"""""""" intellectual abilities reflect the usage of previously learned information and skills, and are least affected by aging. This dichotomy has been upheld in numerous studies of cognitive aging, yet the brain changes underlying these deficits have remained largely elusive. Current theories of functional-anatomic brain organization suggest that many, if not all, higher cortical functions are subserved by interconnected networks of brain regions. The goal of the current proposal is to examine age-related alterations in neural network organization using functional magnetic resonance imaging, and to assess the stability in the Organization of these networks when """"""""fluid"""""""" cognitive domains are compared to """"""""crystallized"""""""" domains. By using a neural network framework to interpret the functional imaging activations this project will look beyond mere increases or decreases in cerebral activations reported in previous studies. Use of newer statistical models (random effects and structural equation modeling) for analyzing the functional imaging data will allow improved assessment of subject by task and interregional interactions respectively. Dr. Gitelman will receive training in imaging statistics and functional imaging experimental design by spending 1 month each year working with Dr. Karl Friston in London. MRI training will be supervised by Dr. Alice Wyrwicz, and will also include Dr. Todd Parrish, both located at Northwestern University. Dr. Kevin LaBar will provide supervision regarding the design of cognitive tasks. Dr. Sandra Weintraub will instruct Dr. Gitelman regarding neuropsychological testing of patient populations. The skills and experience acquired during this project should allow Dr. Gitelman to become an independent investigator in cognitive neuroscience specializing in applications related to functional neuroimaging.
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