CRCNS: Age-related changes to cortical dynamics underlying working memory

灵长类动物的正常衰老通常会导致认知功能受损，特别是工作记忆(WM)。 这一比例在中年开始下降。认知变化与结构和功能变化相关 前额叶皮质(PFC)中的神经元和白质通路，这是大脑中的一个关键区域，在WM中发挥着关键作用。 然而，我们目前对单细胞和通路的变化缺乏机械性的理解 级别会影响网络功能，从而影响WM性能。此外，前额叶皮质只是 导致WM的大脑区域的分布式网络，以及衰老也改变了这些其他区域--特别是 额顶区和视觉区以及远距离区域间连接。这个项目的中心目标是 促进我们对WM背后的计算和神经机制以及年龄的理解- 正常衰老恒河猴模型中这一执行功能的相关变化。具体来说，我们将 测试WM是通过视觉和额顶脑区的协调交互作用而产生的假设， 而与衰老相关的WM下降是由于局部电路动态和区域间的变化造成的 沟通。我们的跨学科方法将结合心理物理学、解剖学和生理学。 理论和计算模型的实验，利用 合作实验室。拟议的研究有以下具体目标：目标1：识别衰老 额顶叶单个神经元、白质通路和静息状态fMRI活动的影响 视觉皮质。目标2：建立一个具有WM功能的多区域计算神经网络模型 从相互作用的分布式电路中出现。目标3：基于模型的解释和实验验证 与年龄相关的WM下降背后的神经机制。

Normal aging in primates often leads to impaired cognitive function, particularly in working memory (WM), which begins to decline in middle-age. Cognitive changes correlate with structural and functional changes to neurons and white matter pathways in the prefrontal cortex (PFC), a brain area that is a key player in WM. However, we currently lack a mechanistic understanding of how the changes at the single-cell and pathway level impact network function and thus WM performance. Moreover, the prefrontal cortex is only one node in a distributed network of brain regions that contributes to WM, and aging also alters these other –particularly fronto-parietal and visual– areas and long-range inter-areal connections. The central goal of this project is to advance our understanding of the computational and neural mechanisms underlying WM as well as the age- related changes to this executive function in the rhesus monkey model of normal aging. Specifically, we will test the hypothesis that WM arises through coordinated interaction of visual and fronto-parietal brain regions, and that aging-related decline in WM results from changes to both local circuit dynamics and inter-area communication. Our interdisciplinary approach will combine psychophysical, anatomical and physiological experiments with theory and computational modeling, taking advantage of the complementary expertise of the collaborating laboratories. The proposed research has the following specific aims: Aim 1: Identify aging effects on individual neurons, white matter pathways and resting state fMRI activity in fronto-parietal and visual cortices. Aim 2: Develop a multi-area computational neural network model in which WM function emerges from interacting distributed circuits. Aim 3: Model-based interpretation and experimental validation of the neuronal mechanisms underlying age-related WM decline.