Role of White Matter Integrity in Age-Related Functional Reorganization

描述（由申请人提供）：克里斯汀·肯尼迪博士的独立之路奖（K99/R 00）的目标，是为了扩大候选人在认知神经科学领域的专业知识，使她能够调查有关白色物质完整性在支持与年龄相关的功能重组中的作用的新问题，并成功地过渡到研究型大学终身职位的独立科学家。结合大脑完整性的结构和功能措施是衰老认知神经科学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了解大脑结构如何影响大脑的功能重组和重组的补偿性质。这个项目的中心目的是调查的作用，白色物质的结构连接在双边招聘，并检查这种功能重组的补偿性质。将使用扩散张量成像、认知性能测量和语义判断功能MRI任务（我们可以从中测量双侧活动指数）在成年人的寿命样本中对假设进行测试。本研究的具体目的是：1）检验白色物质连通性控制年龄相关的双侧募集的假设; 2）联合收割机白色物质完整性和认知表现来确定年龄相关的双侧募集的补偿性质;和3）通过实验操作任务要求，检验白色物质连接性在支持双侧募集中变得比难度更重要的假设增大因为候选人的最终目标是在一所研究型大学获得终身教职，因此该提案的授予将有助于获得该职位，为从指导到独立工作的过渡做好充分准备，并具备管理神经影像实验室所需的专业技能。最后，授予该提案将允许候选人在没有K99/R 00机制的情况下更早地准备和提交重大研究提案（R 01）。 公共卫生相关性：本提案旨在通过检查同一个体的大脑结构和功能，为衰老的认知神经科学领域提供新的知识，以允许对一个的研究为另一个的理解提供信息。结合这些大脑完整性的测量是这一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了解大脑结构如何影响大脑的功能。重要的是，我们开始意识到，衰老的大脑比以前认为的更具可塑性和可塑性，可以进行功能重组，并且有越来越多的证据表明，老年人的这种重组是为了支持更好的认知表现。本提案的目标是进一步了解这一有希望的过程，最终在老年人中看到的功能重组模式，一旦被认为是有益的，可以作为老年人保持良好认知表现的潜在认知干预进行研究，以开发在低功能老年人中产生这种模式的训练任务。将认知健康的年龄延长到生命的尽头将对公共卫生产生重大影响。

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.