2014 — 2016 |
Berry, Anne Shively |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Dopaminergic Modulation of Networks Mediating Cognitive Flexibility in Older Adul @ University of Calif-Lawrenc Berkeley Lab
DESCRIPTION (provided by applicant): The long-range goal of the proposed research is to develop effective, evidenced-based interventions for remediating cognitive decline associated with normal aging. Cognitive flexibility, a component of executive function that allows dynamic switching between tasks, is differentially impaired in older adults. The brain's dopamine system has been linked to cognitive flexibility, and function of this system declines with age. The curren proposal aims to define a possible mechanism by which altered dopamine function influences cognitive flexibility: disrupted communication between prefrontal cortex and striatum. I will employ a within-subjects multimodal imaging approach in young and older adults that will include endogenous measures of dopamine function in striatum (using positron emission tomography (PET) radiotracer 6-[18F]fluoro-L-m-tyrosine (FMT)), structural measures of atrophy within striatum (using structural magnetic resonance imaging (MRI)), and functional network measures between prefrontal cortex and striatum (using functional MRI connectivity analyses at rest and during task-switching). Our preliminary research indicates FMT measures of synthesis capacity increase with age. Increased dopamine synthesis in older adults may reflect compensation to counteract atrophy and other functional declines in the system (e.g. dopamine receptor and transporter downregulation). However, increased synthesis capacity is associated with disrupted cognition, suggesting compensation is either not sufficient or indicates detrimental overcompensation. The current experiments are a necessary first step in prescribing future therapeutic interventions, as they will define the functional significance of age-related increases in dopamine synthesis. My proposed research will test the following hypotheses: (1) Greater cognitive flexibility will be related to greater striatal volume, but this effect will be mediated by dopamine function as measured by FMT-PET, (2) Older adults will have decreased prefrontal cortex-striatal functional connectivity strength measured at rest, but that dopamine function will account for these age differences, and (3) Older adults will show less prefrontal cortex-striatal functional connectivity during task switching relative to young adults, and that connectivity differences mediate the effect of dopamine on cognitive flexibility. Together, the proposed experiments will contribute to a model establishing how age-related structural atrophy leads to dopaminergic dysregulation, which, in turn, disrupts functional network activity to cause cognitive deficits. This research area holds great promise for impacting public health, through eventual clinical applications for age-related cognitive decline as well as disorders associated with dopaminergic dysfunction such as schizophrenia. My proposed research will provide me with training integral to my development as a translationally-focused, multidisciplinary researcher. I will gain valuable experience in PET imaging and in cognitive aging research during my training with Dr. William Jagust, and will take advantage of the rich academic resources available through Lawrence Berkeley National Laboratory and UC Berkeley.
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0.973 |
2018 — 2021 |
Berry, Anne Shively |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Age Effects On Memory and Reward Systems in Decision Making @ University of Calif-Lawrenc Berkeley Lab
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.
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0.973 |