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

CRCNS：工作记忆背后的皮质动力学与年龄相关的变化

基本信息

批准号：
10260597
负责人：
JENNIFER I LUEBKE
金额：
$ 18.66万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-11 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10260597
关键词：
Action Potentials Address Affect Age Aging Anatomy Anisotropy Architecture Area Axon Behavioral Brain Brain region Cells Cognitive Cognitive aging Communication Communities Computer Models Data Data Set Demyelinations Diffusion Diffusion Magnetic Resonance Imaging Electrophysiology (science)Fiber Freedom Functional Magnetic Resonance Imaging Goals Hippocampus (Brain)Impaired cognition Impairment In Vitro Incidence Individual Instruction Internet Interneurons Laboratories Macaca mulatta Magnetic Resonance Imaging Measurement Measures Memory Memory Loss Memory impairment Mission Modeling Monkeys Myelin Neural Network Simulation Neuronal Dysfunction Neurons Neurosciences Nodal Parietal Pathway interactions Performance Physiological Population Prefrontal Cortex Primates Principal Investigator Productivity Property Prosencephalon Psychophysics Quality of life Research Resources Rest Short-Term Memory Slice Structure Synapses Testing Validation Visual Visual Cortex age effect age related aged aging population artificial neural network base biophysical model brain health cognitive change cognitive function cohort executive function experimental study extrastriate visual cortex frontal lobe functional restoration hippocampal pyramidal neuron insight interdisciplinary approach middle age neocortical network models neuromechanism normal aging predictive modeling prevent public health relevance relating to nervous system spectrograph targeted treatment theories validation studies white matter

项目摘要

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.

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），中年时开始衰退认知变化与结构和功能变化相关。前额叶皮层 (PFC) 中的神经元和白质通路，前额叶皮层是 WM 的关键区域。然而，我们目前对单细胞和途径的变化缺乏机制理解。水平影响网络功能，从而影响 WM 性能。此外，前额叶皮层只是其中的一个节点。有助于 WM 的大脑区域的分布式网络，而衰老也会改变其他区域——尤其是该项目的中心目标是额顶叶和视觉区域以及远程区域间连接。增进我们对 WM 以及年龄相关计算和神经机制的理解具体来说，我们将在正常衰老的恒河猴模型中与这种执行功能相关的变化。检验 WM 通过视觉和额顶叶大脑区域的协调相互作用产生的假设，与老化相关的 WM 下降是由于本地电路动态和区域间的变化造成的我们的跨学科方法将结合心理物理学、解剖学和生理学。利用理论和计算模型的互补专业知识进行实验合作实验室提出的研究有以下具体目标：目标 1：识别衰老。对个体神经元、白质通路和额顶叶和静息态功能磁共振成像活动的影响目标 2：开发一个多区域计算神经网络模型，其中 WM 函数目标 3：基于模型的解释和实验验证来自交互的分布式电路。与年龄相关的 WM 下降的神经机制。