Age effects on memory and reward systems in decision making

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Project Summary Aging is accompanied by profound changes in neurochemical systems as well as accumulation of aggregated proteins. To date, the influence of these processes on cognition has been studied in isolation. The proposed research takes novel steps to bridge these fields to develop an integrative model of how changes across multiple neural systems interact to affect high-level decision making in aging. Candidate and career goals: This project will support the candidate’s essential training and development in the field of cognitive aging, with a particular focus on how decline in reward and memory systems interact to contribute to decision making ability. The candidate has a strong track record of research defining the functional mechanisms by which neuromodulators shape cognition. To support the candidate in launching a sustainable, cross-disciplinary independent research program, two expert mentors will provide individualized training. First, the candidate will train in the field of the neuroeconomics and financial decision making, which she will apply to the field of cognitive aging. Second, the candidate will train in PET methods for assessing Alzheimer’s disease pathology and accompanying medial temporal lobe (MTL) memory function in older adults. This novel research program will capitalize on the candidate’s established expertise while developing critical skills to connect two important lines of cognitive aging research. Environment: The exceptional resources and scientific community at Lawrence Berkeley National Laboratory and UC Berkeley Haas School of Business provide and ideal environment to foster the candidate’s development into an innovative and successful independent investigator. The candidate will have access to state-of-the-art human neuroimaging technology and will be supported by a rich institutional culture promoting creative, cross-disciplinary collaborations. Research activity: Aging is accompanied by 1) dysfunction of the dopamine system, which affects the response to rewards in ventral striatum, and 2) aggregation of hyperphosphorylated tau, associated with MTL degeneration and memory disruption. The proposed K99 studies will delineate the independent and interactive roles of these processes in modulating central components of financial decision making: reward learning and memory. These studies will combine PET imaging in healthy older adults, a novel laboratory task designed specifically to probe striatal-MTL interactions, and a validated measure of real-world financial capacity. The proposed R00 studies will pair the laboratory task with functional MRI to define the patterns of activation and network activity between striatum and MTL that underlie age-related disruption in performance and best predict individual differences in real-world financial capacity. Together, these studies will contribute to new models of how cross-system interactions influence high-level cognition in aging while identifying potential targets for remediating decline.