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

描述(申请人提供)：本项目的目标是阐明涉及自上而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改变。自上而下调制是指我们能够将注意力集中在相关的感觉信息上，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。它认为，自上而下调制背后的神经网络是感觉和远端皮质之间的远程连接。此外，前额叶皮质(PFC)和视觉联想皮质(VAC)被认为是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了变化。因此，本项目将重点研究注意控制影响记忆时PFC-VAC网络内的相互作用，并评估正常衰老后可能发生的变化。具体目标1：描述工作记忆任务中PFC-VAC网络的时空特性。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质之间的远程相互神经影响的性质。我假设PFC通过抑制和增强神经活动而对VAC产生可分离的调制活动。具体目标2：评估正常老化引起的PFC-VAC网络的变化。第二个实验将使用与实验1相同的范式和解决相同的问题；然而，与实验1中的较年轻(18-35岁)人群相比，被试群体将由年龄较大(60-75岁)的成年人组成。因此，可以通过观察年龄相关变化来确定PFC在调节视觉工作记忆中的作用的概括性。我假设，由于较少的抑制和更多的补偿机制，老年人将表现出更广泛的分布处理网络。与公共健康相关：为自上而下的调制服务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朝着开发可能减轻这一负担的干预措施迈出的关键一步。

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.