Candidate and career goals: The project will support the candidate's essential training and development as an independent investigator of the cognitive neuroscience of long-term memory with a particular focus on how age-related decline in memory is associated with changes in brain function. Training in the principles of neuropsychological assessment and neuropathology related to patients with dementia will fill out the candidate's preparation for the proposed research activities. One of the candidate's goals is to learn how to integrate multiple methodologies in a new approach to long-term memory research. Results from multiple methodologies converge on a more complete understanding of how functional brain networks support memory retrieval. Three mentors with distinct areas of expertise will advise the candidate on different aspects of the proposed activities, including essential training in neuropsychological assessment, advanced neuroimaging analysis techniques and translation of experimental work into diagnostic tools for clinical populations. The candidate has established a record of productivity with impactful, original research that examines long-term memory retrieval. The proposed research in behavioral neuroscience, and its translation to diagnostic tools for patients with Mild Cognitive Impairment (MCI), will provide new and important insights about how neural networks support recognition memory. Environment: The exceptional resources and scientific community at UCSF make the university an ideal environment to foster the candidate's development into a successful and creative independent investigator. These institutional resources will give the candidate daily opportunities for interaction with distinguished experimental and clinical researchers from various disciplines. The new Neurosciences Building brings together under one roof many of the key resources needed for the candidate's advanced training (i.e., co- mentors, state-of-the-art neuroimaging equipment and the Memory &Aging Center). Courses and services from the UCSF Clinical and Translational Science Institute are available to the candidate to accelerate his aims to make results from basic memory research more useful for clinical diagnosis of patients with amnestic MCI and different phenotypes of dementia. Research activity: A new psychometric paradigm will be used to acquire objective measures of performance on tests of explicit recognition memory. Results will be interpreted using a neural-computational model of processes (i.e., pattern completion and separation) that underlie generalization and discrimination in recognition memory. Groups of younger and older adults will complete memory tests in the MRI scanner while their functional neural data are collected. Within-group analyses of associations between behavioral and fMRI results will elucidate the functional neural networks that support recognition memory- in particular, high fidelity memory. Between-group comparisons will reveal alterations in the functional networks associated with age- related decline in memory performance. The behavioral paradigm used in the neuroimaging studies will be translated to a clinical tool useful in objective assessment of dementia patients'recognition memory. Finally, additional experiments with younger adults will use repetitive TMS to test the causal role of cortical regions of interest in the functional memory networks.
Decline in vivid, detailed memory is a cardinal sign of the onset of dementia and represents one of the most disruptive alterations in cognitive function suffered by approximately one-half of the population older than 65 years of age. Improved understanding of how memory declines over the course of aging, therefore, has great impact for public health. The proposed research in behavioral neuroscience, and its translation to diagnostic tools, will provide new and important insights about how the decline of memory in aging is associated with changes in brain function.