Role of White Matter Integrity in Age-Related Functional Reorganization

白质完整性在年龄相关功能重组中的作用

• 批准号: 8073151
• 负责人: Kristen M. Kennedy
• 金额: $ 8.95万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2012-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8073151
• 关键词: Adult; Affect; Age; Aging; Aging-Related Process; Area; Award; Bilateral; Brain; Brain region; Cerebrum; Cognition; Cognitive; Cognitive aging; Communication; Complex; Contralateral; Corpus Callosum; Diffusion Magnetic Resonance Imaging; Distant; Doctor of Philosophy; Elderly; Faculty; Fiber; Functional Magnetic Resonance Imaging; Goals; Individual; Individual Differences; Intervention; Judgment; Knowledge; Longevity; Measures; Mediating; Mentors; Modeling; Nature; Parietal; Parietal Lobe; Participant; Pathway interactions; Pattern; Performance; Phase; Plastics; Positioning Attribute; Process; Psyche structure; Public Health; Recruitment Activity; Relative (related person); Research; Research Design; Research Proposals; Role; Sample Size; Sampling; Scientist; Secure; Semantics; Staging; Structure; Synaptic Transmission; Testing; Training; Universities; Work; age effect; age group; age related; aged; aging brain; association cortex; cognitive neuroscience; gray matter; indexing; middle age; neural recruitment; neuroimaging; normal aging; novel; phase change; public health relevance; relating to nervous system; response; skills; white matter; young adult

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.

描述（由申请人提供）：克里斯汀·肯尼迪博士获得独立之路奖 (K99/R00) 的目的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与年龄相关的功能重组中的作用的新问题，并成功过渡为研究型大学终身教授职位的独立科学家。将大脑完整性的结构和功能测量结合起来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深入地了解大脑结构如何影响大脑的功能重组以及该重组的补偿性质。该项目的中心目标是研究白质结构连接在双边招募中的作用，并检查这种功能重组的补偿性质。这些假设将在成年人的生命周期样本中进行测试，使用弥散张量成像、认知表现测量和语义判断功能 MRI 任务，从中我们可以测量双边活动指数。该提案的具体目标是：1）检验白质连接控制与年龄相关的双边招募的假设； 2）结合白质完整性和认知表现来确定与年龄相关的双侧募集的补偿性质； 3）通过实验操纵任务要求来检验这样的假设：随着难度的增加，白质连接在支持双边招募方面变得更加重要。由于候选人的最终目标是在研究型大学获得终身教授职位，因此获得该提案将有助于获得该职位，为从指导工作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，与没有 K99/R00 机制的情况相比，该提案的授予将使候选人能够更早地准备和提交重大研究提案 (R01)。 公共健康相关性：本提案旨在通过检查同一个体的大脑结构和功能，为衰老认知神经科学领域提供新知识，以便通过研究一个人来了解另一个人。将这些大脑完整性的测量方法结合起来是该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，更容易进行功能重组，并且有越来越多的证据表明，老年人的这种重组可以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，就可以作为老年人的潜在认知干预进行研究，以保持良好的认知表现，以开发在功能较低的老年人中产生这种模式的训练任务。将认知健康年限延长至生命终结将对公共健康产生重大影响。

项目成果

Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

• DOI: 10.1093/cercor/bhaa243
• 发表时间: 2021-01-01
• 期刊: Cerebral cortex (New York, N.Y. : 1991)
• 作者: Boylan MA;Foster CM;Pongpipat EE;Webb CE;Rodrigue KM;Kennedy KM
• 通讯作者: Kennedy KM

Frontostriatal white matter connectivity: age differences and associations with cognition and BOLD modulation.

额纹状体白质连接：年龄差异以及与认知和 BOLD 调节的关联。

• DOI: 10.1016/j.neurobiolaging.2020.05.014
• 发表时间: 2020
• 期刊: Neurobiology of aging
• 影响因子: 4.2
• 作者: Webb,ChristinaE;Hoagey,DavidA;Rodrigue,KarenM;Kennedy,KristenM
• 通讯作者: Kennedy,KristenM

Increasing beta-amyloid deposition in cognitively healthy aging predicts nonlinear change in BOLD modulation to difficulty.

• DOI: 10.1016/j.neuroimage.2018.08.017
• 发表时间: 2018-12
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Kennedy KM;Foster CM;Rodrigue KM
• 通讯作者: Rodrigue KM

Functional magnetic resonance imaging data of incremental increases in visuo-spatial difficulty in an adult lifespan sample.

成人寿命样本中视觉空间难度增量增加的功能磁共振成像数据。

• DOI: 10.1016/j.dib.2017.01.004
• 发表时间: 2017
• 期刊: Data in brief
• 影响因子: 1.2
• 作者: Kennedy,KristenM;Rieck,JennyR;Boylan,MariaA;Rodrigue,KarenM
• 通讯作者: Rodrigue,KarenM

Cortical thickness mediates the relationship between DRD2 C957T polymorphism and executive function across the adult lifespan.

皮质厚度介导 DRD2 C957T 多态性与成人寿命执行功能之间的关系。

• DOI: 10.1007/s00429-020-02169-5
• 发表时间: 2021-01
• 期刊: Brain structure & function
• 影响因子: 3.1
• 作者: Miranda GG;Rodrigue KM;Kennedy KM
• 通讯作者: Kennedy KM