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

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研究与年龄相关的工作记忆(WM)差异背后的神经基础，该假说指出，皮层功能效率的降低是老年人与年轻人处理速度较慢的基础，这反过来又调节了与年龄相关的认知能力下降。这项拟议的研究将结合使用扩散张量成像(DTI)和功能磁共振成像(FMRI)来评估白质完整性对神经效率的贡献，从而推进这一假说。与年龄相关的减慢被认为是认知老化的原因，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得到系统的研究。FMRI研究表明，前额叶(PFC)和顶叶皮质调节WM操作，这些区域的活动受WM操作速度和加工速度的调节。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，这可能是西医年龄组差异的基础。这项拟议的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活动来衡量)是否会在衰老过程中调节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潜在大脑结构上的差异，例如任务相关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，并与老年人的处理速度和WM受损有关。这项拟议的研究将首次检验与任务相关的额顶束完整性的年龄组差异是否与神经效率有关，以及这是否解释了WM成绩的年龄组差异(具体目标2)。这些长距离的直接联系可能更容易受到与年龄相关的完整性下降的影响，这可能会导致对间接联系(即额叶-丘脑-顶叶)的依赖程度增加，以获得最佳的任务绩效。因此，这项研究还将评估间接神经束完整性、神经效率和衰老过程中的WM表现之间的关系(具体目标3)。这项研究的结果将有助于培养成功的衰老。工作记忆是各种日常技能不可或缺的一部分，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化老年认知功能的认知训练和药物治疗计划提供信息。随着我们人口中老年人数量的稳步增加，这一目标变得越来越重要。 公共卫生相关性：这项研究的结果与成功老龄化有关。工作记忆通过使人们能够执行包括推理、语言理解和心算在内的各种日常技能来促进独立生活。因此，确定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物治疗计划是重要的。随着我们人口中老年人数量的稳步增加，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.