Brain Network Mechanisms of Aging-Related Cognitive Decline

衰老相关认知衰退的脑网络机制

• 批准号: 10115559
• 负责人: Michael William Cole
• 金额: $ 38.72万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115559
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Amyloid beta-Protein; Behavior; Brain; Brain region; Cognition; Cognitive deficits; Elderly; Functional Magnetic Resonance Imaging; Goals; Grain; Impaired cognition; Individual Differences; Knowledge; Learning; Life; Link; Liquid substance; Literature; Measures; Mediating; Memory impairment; Meta-Analysis; Methods; Movement; Network-based; Neurodegenerative Disorders; Outcome; Pathway interactions; Play; Process; Property; Public Health; Research; Rest; Role; Route; Series; System; Task Performances; Testing; Time; Training; base; cognitive ability; cognitive control; cognitive process; cognitive reserve; cognitive task; cognitive training; experience; healthy aging; improved; improved outcome; innovation; long term memory; relating to nervous system; tool

PROJECT SUMMARY/ABSTRACT Aging-related cognitive decline has been independently linked to alterations in resting-state functional connectivity (RSFC) and cognitive task activations using functional MRI (fMRI), yet it is now well established that there is a strong statistical relationship between RSFC and task activations. This is despite these being quite distinct measures: RSFC is calculated as correlations among distributed brain activity time series during rest, while task activations are localized brain activity amplitude changes during active task performance. The network mechanisms underlying the RSFC-activation relationship are unknown, yet understanding this relationship would clarify how aging alters both RSFC and cognitive task activations. For RSFC, linking to cognitive task activations may help explain why RSFC is associated with cognitive processes despite being measured independently of tasks testing those processes. For cognitive task activations, linking to RSFC may bring a unified network-based understanding to the varied aging-related activation changes identified across many brain regions and tasks. Thus, there is a critical need to determine the network mechanisms underlying the relationship between RSFC and cognitive task activations. Without such knowledge, obtaining a unified understanding of the neural basis of aging-related cognitive decline is unlikely. The overall objective of this proposal is to identify network mechanisms that can account for the alterations in both RSFC and cognitive task activations that occur with aging-related decline (from ages 18-28 to 65-75) of cognitive control abilities among healthy older adults. This focus on cognitive control reflects its importance to adaptive, goal-directed behavior in daily life. Further, cognitive control network (CCN) regions have RSFC network “hub” properties well suited to regulate general cognitive ability. Of particular relevance to aging, cognitive control is one of the abilities most affected by both healthy aging and Alzheimer’s disease, and it plays a role in long-term memory deficits (a key feature of Alzheimer’s disease). This proposal’s central hypothesis is that aging-related alterations in RSFC reflect changes in intrinsic network pathways that influence brain activations during task performance, and hence mediate disruption of cognitive control abilities. Three approaches will be utilized across three aims to test our central hypothesis. Briefly, the first will utilize an innovative approach to predict activation abnormalities based on RSFC abnormalities in healthy older adults. The second will utilize individual differences to determine the contribution of CCN hub disruption to aging-related cognitive decline. The third will utilize the established influence of cognitive training on RSFC to investigate the role of functional network plasticity in aging-related cognitive decline. This project is expected to markedly improve understanding of the brain network basis of cognitive decline from healthy aging, in addition to improving general understanding of the large-scale network mechanisms underlying cognition.

项目概要/摘要 与衰老相关的认知能力下降与静息状态功能的改变独立相关 使用功能性 MRI (fMRI) 进行连通性 (RSFC) 和认知任务激活，但现已得到很好的确立 RSFC 和任务激活之间存在很强的统计关系。尽管有这些 相当不同的衡量标准：RSFC 计算为分布式大脑活动时间序列之间的相关性 休息时，任务激活是主动任务执行过程中局部大脑活动幅度的变化。这 RSFC-激活关系背后的网络机制尚不清楚，但了解这一点 这种关系将阐明衰老如何改变 RSFC 和认知任务激活。对于 RSFC，链接到 认知任务激活可能有助于解释为什么 RSFC 与认知过程相关，尽管 独立于测试这些流程的任务进行测量。对于认知任务激活，链接到 RSFC 可能 为跨领域确定的各种与衰老相关的激活变化提供基于网络的统一理解 许多大脑区域和任务。因此，迫切需要确定底层的网络机制 RSFC 和认知任务激活之间的关系。如果没有这些知识，就无法获得统一的 了解与衰老相关的认知能力下降的神经基础是不可能的。本次活动的总体目标 建议是确定可以解释 RSFC 和认知变化的网络机制 随年龄增长（从 18-28 岁到 65-75 岁）认知控制能力下降而发生的任务激活 在健康的老年人中。对认知控制的关注反映了其对适应性、目标导向的重要性 日常生活中的行为。此外，认知控制网络（CCN）区域具有 RSFC 网络“中心”属性 非常适合调节一般认知能力。认知控制与衰老特别相关，是其中之一 受健康衰老和阿尔茨海默病影响最大的能力，它在长期记忆中发挥着作用 缺陷（阿尔茨海默病的一个关键特征）。该提案的中心假设是与衰老相关的 RSFC 的改变反映了影响任务期间大脑激活的内在网络通路的变化 表现，从而介导认知控制能力的破坏。将使用三种方法 跨越三个目标来检验我们的中心假设。简而言之，第一个将利用创新方法来预测 基于健康老年人 RSFC 异常的激活异常。第二个将利用个人 差异以确定 CCN 中枢破坏对衰老相关认知能力下降的影响。第三个会 利用认知训练对 RSFC 的既定影响来研究功能网络的作用 与衰老相关的认知能力下降的可塑性。该项目预计将显着提高对 除了提高对健康衰老的总体理解之外，大脑网络也是健康衰老导致认知能力下降的基础 认知背后的大规模网络机制。