Neurocognitive Aging of Memory and Executive Processes

工作记忆包括在短时间内在线保存信息的存储机制和操作存储内容以满足更高认知需求的执行过程。工作记忆随着年龄的增长而急剧下降，然而这种下降背后的认知和神经机制尚未被确定。我们提出了一项结合行为、功能和结构神经成像分析的研究计划，以调查工作记忆存储和执行功能的年龄差异。每个年龄组的优秀者和劣秀者的比较将被用来区分神经认知过程的连续性，这种连续性贯穿整个生命周期，与衰老特有的定性变化。工作记忆回路包括几个顶叶和额叶区域，其中左半球主要负责语言工作记忆，右半球主要负责空间工作记忆。来自正电子发射断层扫描研究的证据表明，衰老(1)改变了语言和空间工作记忆任务所招募的区域的偏侧性，(2)导致前额叶区域的招募，而这些区域在年轻的大脑中并不一定参与。拟议的研究有两个主要目标。首先，我们想要确定年轻人和老年人的侧性和前额叶激活差异的功能意义。我们将使用事件相关的功能磁共振成像来识别与这些年龄差异相关的认知操作，比较语言和空间工作记忆任务，强调存储。这些研究构成了目标1，并为目标2-3中的执行过程调查提供了基础。相当多的证据表明，执行过程和调节它们的额叶区域特别容易受到衰老的影响。因此，我们的第二个主要目标是研究年龄对工作记忆中两个执行过程的影响：(1)时间背景的编码和(2)竞争事件干扰的解决。对于每个过程，我们的目标是确定潜在的神经机制，确定执行机制是否有助于编码、维持和检索过程，确定这些机制在语言和空间材料上的差异程度，并确定衰老是否对这些机制施加选择性影响，这些机制本质上是代偿性的，还是导致认知表现受损。通过获得与工作记忆有关的大脑区域的结构测量，我们打算通过功能磁共振成像（fMRI）确定与年龄相关的萎缩对认知表现和神经基质改变的贡献。

Working memory consists of storage mechanisms that hold information on-line for brief intervals and executive processes that can manipulate the stored contents in service of higher cognitive demands. Working memory declines dramatically with age, however the cognitive and neural mechanisms underlying this decline have yet to be identified. We propose a program of research that combines behavioral, functional, and structural neuroimaging analyses to investigate age differences in working memory storage and executive functions. Comparisons of good and poor performers in each age group will be used to distinguish between a continuum of neurocognitive processes, with continuity across the lifespan, versus qualitative changes unique to aging. The working memory circuitry includes several parietal and frontal regions, with left hemisphere prominence for verbal working memory and right hemisphere prominence for spatial working memory. Evidence from positron emission tomography studies indicates that aging (1) alters the laterality of regions recruited by verbal and spatial working memory tasks, and (2) leads to the recruitment of prefrontal sites under conditions that do not necessarily engage these regions in the younger brain. The proposed research has 2 major goals. First, we want to identify the functional significance of the laterality and prefrontal activation differences between younger and older adults. We will use event-related fMRI to identify the cognitive operations associated with these age differences comparing verbal and spatial working memory tasks that emphasize storage. These studies constitute Aim 1 and provide the foundation for investigating executive processes in Aims 2-3. Considerable evidence indicates that executive processes and the frontal regions that mediate them are particularly vulnerable to aging. Therefore, our second major goal is to examine age effects on two executive processes in working memory: (1) the coding of temporal context and (2) the resolution of interference from competing events. For each process our goals are to identify the underlying neural mechanisms, to determine whether the executive mechanisms contribute to encoding, maintenance, and retrieval processes, to determine the extent to which these mechanisms differ for verbal and spatial materials, and to identify whether aging exerts selective effects on these mechanisms that are compensatory in nature or lead to impaired cognitive performance. By obtaining structural measurements of brain regions implicated in working memory, we intend to determine the contribution of age-related atrophy to cognitive performance and to alterations in the neural substrates as revealed through fMRI.