Age Related Changes in the Top-Down Modulation of Working Memory

描述（由申请人提供）：该项目的目标是阐明参与自顶向下调制的神经网络组件的时空特性，并评估这些网络如何因正常老化而变化。自上而下调节指的是我们将注意力集中在相关的感官信息上，而忽略无关的刺激，从而提高我们在工作记忆等认知任务中的表现。人们已经假设，自上而下调节的神经网络是感觉皮层和远端皮层之间的远程连接。此外，前额叶皮层（PFC）和视觉关联皮层（VAC）已被确定为参与视觉工作记忆的分布式网络的组成部分，并被认为在正常衰老过程中功能发生变化。因此，本项目将重点关注PFC-VAC网络内部的相互作用，因为注意控制影响记忆，并评估正常衰老后可能发生的变化。具体目标1：表征PFC-VAC网络在工作记忆任务中的时空特性。通过使用fMRI引导的TMS/EEG记录方法，可以定位、记录和干扰网络活动，以研究内在连通性和功能的因果效应。事件相关电位，频谱和双变量分析将有助于表征额叶和视觉皮层之间的远程互反神经影响的性质。我假设PFC通过抑制和增强神经活动对VAC产生可分离的调节活动。具体目标2：评估PFC-VAC网络因正常老化而发生的变化。第二个实验将使用与实验1相同的范式并解决与实验1相同的问题；然而，受试者群体将由老年人（60-75岁）组成，而不是实验1中的年轻人（18-35岁）。因此，PFC在调节视觉工作记忆中的作用可以通过观察年龄相关的变化来确定。我推测，由于抑制机制较少，代偿机制较多，老年人将表现出更广泛分布的加工网络。公共卫生相关性：服务于自上而下调节的网络的连通性和功能的差异可能是与衰老相关的广泛认知缺陷的基础。对这些基本神经机制的探索是开发可能减轻这种负担的干预措施的关键一步。

DESCRIPTION (provided by applicant): The goal of this project is to elucidate the spatio-temporal properties of neural network components involved in top-down modulation and evaluate how these networks may change due to normal aging. Topdown modulation refers to our ability to focus attention on pertinent sensory information and ignore irrelevant stimuli thereby improving our performance on cognitive tasks such as working memory. It has seen hypothesized that the neural networks underlying top-down modulation are long-range connections between sensory and distal cortices. Moreover, the prefrontal cortex (PFC) and the visual association cortex (VAC) have been identified as components of a distributed network involved in visual working memory and have been suggested to change in functionality during normal aging. Therefore, this project will focus on the interactions within the PFC-VAC network as attentional control influences memory and evaluate what changes may occur after normal aging. Specific Aim 1: Characterize the spatio-temporal properties of the PFC-VAC network during a working memory task. Through the use of an fMRI guided TMS/EEG recording approach, network activity may be localized, recorded and perturbed to study the causal effects of the intrinsic connectivity and functionality. Event-related potential, spectral and bivariate analysis will help characterize the nature of the long-range reciprocal neural influences between the frontal and visual cortices. I hypothesize the PFC yields separable modulatory activity on the VAC through suppression and enhancement of neural activity. Specific Aim 2: Evaluate changes in the PFC-VAC network due to normal aging. The second experiment will utilize the same paradigm and address the same questions as Experiment 1; however, the subject population will consist of older (60-75 years of age) adults as opposed to the younger (18-35 years of age) population in Experiment 1. Thus, generizability of a PFC role in modulating visual working memory may be determined through the observation of age related changes. I hypothesize that older adults will display a more widely distributed processing network due to fewer suppression and more compensatory mechanisms. PUBLIC HEALTH RELEVANCE: Differences in the connectivity and functionality of networks subserving top-down modulation may underlie a wide range of cognitive deficits associated with aging. The exploration of these basic neuralmechanisms is a critical step towards developing interventions that may alleviate this burden.