The role of white matter integrity in neural efficiency and cognitive aging

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老化的神经生物学基础。将使用神经效率假说的框架来检查与年龄相关的工作记忆（WM）差异的神经基质，该假说指出，皮质功能效率降低是老年人与年轻人相比处理速度较慢的基础，这反过来又介导了与年龄相关的认知下降。拟议的研究将推进这一假设，使用扩散张量成像（DTI）结合功能磁共振成像（fMRI），以评估白色物质的完整性对神经效率的贡献。已经提出了与年龄相关的减缓来解释认知老化，包括与年龄相关的WM下降。然而，这种效应的神经基础尚未得到系统的研究。功能磁共振成像研究表明，前额叶（PFC）和顶叶皮层介导的WM性能，并在这些地区的活动调制WM性能的速度和加工速度。我们认为，加工速度和神经活动的大小之间的关系可能反映了神经功能的效率，这可能是年龄组差异的基础工作记忆。该实验将是第一个直接测试神经效率的个体差异（测量为处理速度相关的PFC活动）是否介导衰老过程中WM的下降（具体目标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年龄组在底层大脑结构上的差异，例如任务相关大脑区域之间的白色连接的完整性。DTI研究表明，额叶白色物质的完整性随着年龄的增长而下降，并且与老年人与年轻人的加工速度和WM受损有关。拟议的研究将是第一个检查是否年龄组的任务相关的额顶叶束的完整性差异与神经效率，这是否解释了年龄组的差异WM性能（具体目标2）。这些长距离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的依赖增加（即，额叶-丘脑-顶叶）以获得最佳任务表现。因此，本研究还将评估间接束完整性、神经效率和衰老中WM性能之间的关系（具体目标3）。这项研究的结果将有助于促进成功的老龄化。工作记忆是各种日常技能的组成部分，包括推理、语言理解和心算。确定最佳表现背后的功能和结构神经机制将为旨在最大限度地提高老年认知功能的认知训练和药理学治疗计划提供信息。随着我国人口中老年人人数的稳步增加，这一目标变得越来越重要。 公共卫生相关性：本研究的结果与成功老化相关。工作记忆通过使人们能够执行各种日常技能，包括推理，语言理解和心算来促进独立生活。因此，识别最佳表现背后的神经机制对于旨在最大化老年认知功能的认知训练和药理学治疗计划非常重要。随着我国人口中老年人人数的稳步增加，这一目标变得越来越重要。

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.