The role of white matter integrity in the neural efficiency hypothesis of cogniti

白质完整性在认知神经效率假说中的作用

• 批准号: 8060228
• 负责人: Ilana Jacqueline Bennett
• 金额: $ 4.76万
• 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: 2010-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8060228
• 关键词: role; white; matter; integrity; neural

DESCRIPTION (provided by applicant): The primary goal of the proposed research is to further understand the neurobiological basis of cognitive aging. Neural substrates underlying age-related working memory (WM) differences will be examined using the framework of the neural efficiency hypotheses, which states that reduced efficiency of cortical functioning underlies slower speed of processing in older versus younger adults, which in turn mediates age- related cognitive declines. The proposed research will advance this hypothesis using diffusion tensor imaging (DTI) in combination with functional magnetic resonance imaging (fMRI) to assess the contribution of white matter integrity to neural efficiency. Age-related slowing has been proposed to account for cognitive aging, including age-related WM declines. However, the neural basis of this effect has not been systematically examined. FMRI research has shown that prefrontal (PFC) and parietal cortex mediate WM performance, and that activity in these regions is modulated by WM performance speed and processing speed. We propose that the relationship between processing speed and the magnitude of neural activity may reflect efficiency of neural functioning, which may underlie age group differences in WM. The proposed experiment will be the first to directly test whether individual differences in neural efficiency, measured as processing speed-related PFC activity, mediates WM declines in aging (Specific Aim 1). The neural efficiency hypothesis further proposes that age-related neural efficiency declines may be due to age group differences in underlying brain structure, such as integrity of white matter connections between task-relevant brain regions. DTI research has shown that integrity of frontal white matter declines with aging, and is associated with impaired processing speed and WM in older versus younger adults. The proposed study will be the first to examine whether age group differences in integrity of task-relevant frontal-parietal tracts relates to neural efficiency, and whether this explains age group differences in WM performance (Specific Aim 2). These long-range direct connections may be more susceptible to age-related declines in integrity, which may lead to increased dependence on indirect connections (i.e., frontal-thalamus-parietal) for optimal task performance. Therefore, this study will also assess relationships among indirect tract integrity, neural efficiency, and WM performance in aging (Specific Aim 3). Results from this study will contribute to fostering successful aging. WM is integral to a variety of everyday skills including reasoning, language comprehension, and mental calculations. Identifying functional and structural neural mechanisms underlying optimal performance will inform cognitive training and pharmacological treatment programs aimed at maximizing cognitive functioning in old age. This goal is becoming increasingly important as the number of older adults in our population steadily rises. PUBLIC HEALTH RELEVANCE: Results from this study are relevant to successful aging. Working memory promotes independent living by enabling people to perform a variety of everyday skills including reasoning, language comprehension, and mental calculations. Thus, identifying the neural mechanisms underlying optimal performance is important for cognitive training and pharmacological treatment programs aimed at maximizing cognitive functioning in old age. This goal is becoming increasingly important as the number of older adults in our population steadily rises.

描述（由申请人提供）：拟议研究的主要目标是进一步了解认知衰老的神经生物学基础。我们将使用神经效率假说的框架来研究与年龄相关的工作记忆（WM）差异背后的神经基质。该假说认为，与年轻人相比，皮层功能效率的降低是老年人处理速度较慢的基础，而这反过来又介导了与年龄相关的认知能力下降。本研究将利用弥散张量成像（DTI）结合功能性磁共振成像（fMRI）来评估白质完整性对神经效率的贡献，从而推进这一假设。与年龄相关的减速被用来解释认知衰老，包括与年龄相关的WM下降。然而，这种效应的神经基础还没有被系统地研究过。功能磁共振成像（FMRI）研究表明，前额叶（PFC）和顶叶皮层调节WM的表现，这些区域的活动受到WM表现速度和处理速度的调节。我们认为处理速度和神经活动强度之间的关系可能反映了神经功能的效率，这可能是WM年龄组差异的基础。该实验将首次直接测试神经效率的个体差异（以处理速度相关的PFC活动衡量）是否介导WM在衰老过程中的下降（Specific Aim 1）。神经效率假说进一步提出，与年龄相关的神经效率下降可能是由于大脑底层结构的年龄组差异，例如与任务相关的大脑区域之间白质连接的完整性。DTI研究表明，额叶白质的完整性随着年龄的增长而下降，并且与老年人和年轻人的处理速度和WM受损有关。该研究将首次研究任务相关额顶叶束完整性的年龄组差异是否与神经效率相关，以及这是否解释了WM表现的年龄组差异（Specific Aim 2）。这些远程直接连接可能更容易受到与年龄相关的完整性下降的影响，这可能导致对间接连接（即额-丘脑-顶叶）的依赖增加，以获得最佳的任务表现。因此，本研究还将评估间接神经束完整性、神经效率和老龄患者WM表现之间的关系（Specific Aim 3）。这项研究的结果将有助于促进成功的老龄化。WM是各种日常技能的组成部分，包括推理、语言理解和心算。识别最佳表现背后的功能和结构神经机制将为认知训练和旨在最大化老年认知功能的药物治疗方案提供信息。随着我国人口中老年人的数量稳步上升，这一目标正变得越来越重要。