fMRI Studies of Age-related Changes in Executive Processing

描述（由申请人提供）：正常的衰老伴随着认知功能的下降，这可能对老年人的生活产生广泛的影响，包括工作、社会交往和管理日常事务，如财务。也许最常见的主观抱怨之一是工作记忆和长期记忆的问题。造成这种与年龄相关的衰退的一个主要因素是执行过程的功能受损，执行过程是在理解、记忆、决策和解决问题等高级认知活动中维持和操纵信息的过程。越来越多的证据表明，前额叶皮层（PFC）在这些认知活动的执行过程中起着至关重要的作用，而且越来越多的证据表明，PFC在参与的过程中显示出功能性组织。也有证据表明，PFC的主要作用是调节大脑其他区域的活动，包括那些参与初始感知和对经历事件的持久表征进行编码的区域。与其他大脑区域相比，衰老对PFC的影响不成比例，结构、功能和代谢变化与认知功能障碍有关。越来越多的报告显示，老年人的认知表现与执行功能敏感的认知任务得分呈正相关，fMRI研究显示，在认知任务（包括评估执行功能的任务）中，PFC和后脑区活动的年龄相关差异。研究执行功能的研究者的一个共同目标是描述PFC的功能组织，包括个体过程、相关功能组和/或在需要控制的任务中某个区域在调节其他区域中的作用。然而，尽管人们对这些话题的兴趣越来越大，对于执行功能的单一可行分类，额叶皮层的特定区域如何映射到特定的执行过程，或者支持它们的动态网络，仍然没有达成一致意见。一个可能的原因是，传统上用于挖掘执行功能的许多实验室任务都很复杂——涉及多个执行过程，并受到不同团队之间潜在战略差异的影响。因此，拟议的项目将使用简单的任务来推进四个广泛的目标：(1)进一步明确执行功能中涉及的组成认知过程；(2)识别其神经基础，包括脑区之间的功能网络；(3)评估衰老对脑区组成过程和潜在神经活动的影响；(4)研究执行功能测量的个体差异如何与与执行过程组成部分相关的大脑活动（和连通性）模式的差异相关联。

DESCRIPTION (provided by applicant): Normal aging is accompanied by reduced cognitive functioning that can have a broad impact on older adults' lives, including work, social interactions, and managing daily tasks such as finances. Perhaps one of the most common subjective complaints is problems with working memory and long term memory. A major factor contributing to such age-related decline is impaired functioning of the executive processes by which information is maintained and manipulated during higher-order cognitive activities such as comprehension, memory, decision-making and problem-solving. There is accumulating evidence converging on the critical role of prefrontal cortex (PFC) in the executive processes involved in such cognitive activities, and there is increasing evidence that PFC shows functional organization with respect to the processes engaged. There is also evidence that a primary role of PFC is to modulate activity in other brain regions, including those involved in initial perception and the encoding of enduring representations of experienced events. Aging disproportionately affects the PFC, compared to other brain regions, and structural, functional, and metabolic changes have been associated with cognitive dysfunction. There are a growing number of reports of positive correlations between older adults' cognitive performance and scores on cognitive tasks sensitive to executive function, and fMRI studies showing age-related differences in PFC and posterior area activity during cognitive tasks, including tasks assessing executive function. A common goal of investigators working on executive function is to characterize the functional organization of PFC with respect to individual processes, groups of related functions, and/or an area's role in modulating other areas during tasks requiring control. Yet, in spite of increasing interest in these topics, there is still little agreement on a single workable taxonomy of executive functions, how specific regions of frontal cortex map onto specific executive processes, or the dynamic networks that support them. One possible reason is that many of the laboratory tasks traditionally used to tap executive functions are complex---involving multiple component executive processes and subject to potential strategy differences across groups. The proposed project will thus use simple tasks to advance four broad aims: (1) To further specify the component cognitive processes involved in executive function; (2) To identify their neural bases, including functional networks between brain regions; (3) To assess how component processes and underlying neural activity are affected by aging; (4) To examine how individual differences in performance on measures of executive function relate to differences in patterns of brain activity (and connectivity) related to component executive processes. PUBLIC HEALTH RELEVANCE: Impaired executive functioning associated with normal aging can have a broad impact on older adults' productivity, physical health and general sense of well-being. With the expected increase in the aging population, normal age-related cognitive decline is a major public health issue. The aim of this project is to further characterize specific executive processes, their neural mechanisms, and the impact of aging on them; such information should aid the development of interventions and biomarkers to evaluate the efficacy of interventions.