Role of White Matter Integrity in Age-Related Functional Reorganization

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DESCRIPTION (provided by applicant): The objectives of this Pathway to Independence Award (K99/R00) for Kristen Kennedy, Ph.D., are to expand the candidate's expertise in the field of cognitive neuroscience, to enable her to investigate novel questions regarding the role of white matter integrity in supporting age-related functional reorganization, and to transition successfully to an independent scientist in a tenure-track position at a research university. Combining structural and functional measures of brain integrity is a major goal in the field of the cognitive neuroscience of aging, and knowledge gained from this study should bring us closer to understanding how brain structure affects the brain's functional reorganization and the compensatory nature of that reorganization. The central aim of this project is to investigate the role of white matter structural connectivity in bilateral recruitment and to examine the compensatory nature of this functional reorganization. The hypotheses will be tested in a lifespan sample of adults using Diffusion Tensor Imaging, measures of cognitive performance, and a semantic judgment functional MRI task from which we can measure a bilateral activity index. The specific aims of this proposal are: 1) To test the hypothesis that white matter connectivity governs age-related bilateral recruitment; 2) To combine white matter integrity and cognitive performance to determine the compensatory nature of age-related bilateral recruitment; and 3) To experimentally manipulate task demands to test the hypothesis that white matter connectivity becomes more important in supporting bilateral recruitment as difficulty increases. Because the candidate's ultimate goal is to secure a tenure-track faculty position in a research-oriented university, award of this proposal will facilitate acquiring that position well-prepared for the transition from mentored to independent work and with the professional skills necessary to manage a neuroimaging lab. Lastly, award of this proposal will allow the candidate to prepare and submit a major research proposal (R01) at an earlier stage than would be possible without this K99/R00 mechanism. PUBLIC HEALTH RELEVANCE: The present proposal seeks to provide new knowledge to the field of cognitive neuroscience of aging by examining brain structure and function in the same individuals to allow the study of one to inform understanding of the other. Combining these measures of brain integrity is a major goal in this field and knowledge gained from this study should bring us closer to understanding how brain structure affects the brain's function. Importantly, we are beginning to realize that the aging brain is more plastic and malleable to functional reorganization than previously believed and there is building evidence that this reorganization in older adults is invoked to support better cognitive performance. The goal of the present proposal is to further understand this promising process, and ultimately the functional reorganization patterns seen in older adults, once deemed beneficial, can be studied as a potential cognitive intervention for older adults to maintain good cognitive performance to develop training tasks that produce this pattern in lower-functioning older adults. Extending the cognitively healthy years toward the end of the lifespan would have significant public health implications.