Role of White Matter Integrity in Age-Related Functional Reorganization

描述（由申请人提供）：Kristen Kennedy博士的独立之路奖（K99/R00）的目标是扩展候选人在认知神经科学领域的专业知识，使她能够研究有关白质完整性在支持年龄相关功能重组中的作用的新问题，并成功过渡到研究型大学的终身职位的独立科学家。结合脑完整性的结构和功能测量是认知神经科学衰老领域的一个主要目标，从这项研究中获得的知识应该使我们更接近于理解大脑结构如何影响大脑的功能重组和这种重组的代偿性质。该项目的中心目标是研究白质结构连接在双侧招募中的作用，并检查这种功能重组的补偿性。这些假设将在成年人的一生样本中进行测试，使用弥散张量成像（Diffusion Tensor Imaging）来测量认知表现，并通过语义判断功能MRI任务来测量双侧活动指数。本提案的具体目的是：1)验证白质连接控制与年龄相关的双侧招募的假设；2)结合脑白质完整性和认知表现来确定年龄相关双侧招募的代偿性质；3)通过实验操纵任务需求，验证随着难度的增加，白质连通性在支持双侧招募方面变得更加重要的假设。由于候选人的最终目标是在研究型大学获得终身教职，因此本提案的奖励将有助于获得该职位，为从指导工作过渡到独立工作做好充分准备，并具备管理神经影像学实验室所需的专业技能。最后，该提案的奖励将允许候选人在没有K99/R00机制的情况下，在更早的阶段准备和提交主要研究提案（R01）。

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.