Influences of Environmental Geometry and Aging on Cognitive Mapping Mechanisms

环境几何和衰老对认知映射机制的影响

基本信息

批准号：
10441684
负责人：
Thackery Ian Brown
金额：
$ 44.23万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10441684
关键词：
Address Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer’s disease biomarker Biological Markers Brain Cells Code Cognition Cognitive Complex Computer Models Data Dementia Disease Environment Euclidean Space Foundations Functional Magnetic Resonance Imaging Functional disorder Geometry Goals Hippocampus (Brain)Human Hybrids Impaired cognition Impairment Individual Intervention Knowledge Learning Life Link Literature Location Machine Learning Maps Measures Memory Methods Modeling Motion Neurons Nobel Prize Pattern Performance Persons Research Research Personnel Rodent Route Shapes Signal Transduction Space Perception Structure System Techniques Testing Time Update Visual Cortex Work age related aged apolipoprotein E-4 base cohort design entorhinal cortex experience experimental study graph theory healthy aging insight mild cognitive impairment neuroimaging neuromechanism novel pre-clinical preference programs psychologic relating to nervous system spatial memory spatial relationship statistical learning theories virtual virtual reality way finding young adult

Address Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer’s disease biomarker Biological Markers Brain Cells Code Cognition Cognitive Complex Computer Models Data Dementia Disease Environment Euclidean Space Foundations Functional Magnetic Resonance Imaging Functional disorder Geometry Goals Hippocampus (Brain)Human Hybrids Impaired cognition Impairment Individual Intervention Knowledge Learning Life Link Literature Location Machine Learning Maps Measures Memory Methods Modeling Motion Neurons Nobel Prize Pattern Performance Persons Research Research Personnel Rodent Route Shapes Signal Transduction Space Perception Structure System Techniques Testing Time Update Visual Cortex Work age related aged apolipoprotein E-4 base cohort design entorhinal cortex experience experimental study graph theory healthy aging insight mild cognitive impairment neuroimaging neuromechanism novel pre-clinical preference programs psychologic relating to nervous system spatial memory spatial relationship statistical learning theories virtual virtual reality way finding young adult

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项目摘要

PROJECT SUMMARY | Spatial navigation is fundamental to survival, and entorhinal cortex (EC) function may be fundamental to forming and remembering cognitive maps. The Nobel Prize-winning discovery that EC neurons map environments with grid-like signals has given rise to a class of theories that grid-like metrics from EC facilitate spatial orientation, planning, and navigation to goals. Deficits in these same navigational abilities are a hallmark of both healthy aging and Alzheimer’s-related dementia (ADRD), and EC dysfunction is one of the earliest effects of Alzheimer’s disease and is associated with pre-clinical cognitive decline as well. However, at this time, despite convergent evidence that EC is central to memory and cognitive mapping, how human EC contributes to spatial memory mechanisms remains largely theoretical, and how grid-like signal declines (that have been observed in aging and as a pre-clinical biomarker for Alzheimer’s disease in APOE-ε4 carriers) can contribute to declines in spatial ability in aging and ADRD remains remarkably poorly understood. This proposal will leverage several powerful virtual-navigation and fMRI paradigms to address three gaps in the literature: Aim 1 is to understand how the structure of environments is represented in the human brain. Extensive psychological evidence demonstrates that environmental barriers fragment and distort people’s memory and sense of space. Aim 1 will address why - testing strong predictions that EC encodes spatial metrics that humans use to orient and locate themselves in space, and that barriers shape people’s sense of space in part by anchoring and shaping the spatial metrics from EC. Aim 2 is to address how spatial signals in EC interact with the hippocampus, and contribute to hippocampal-dependent memory. It is believed that the hippocampus builds relational maps of different aspects of our life. The proposed studies will test this, and theories that grid- like EC signals inform 1) how different parts of our environment are segregated in hippocampal memory, but also 2) how the hippocampus encodes similarities between navigational experiences. Aim 3 is to test a neural- mechanistic model of how the hippocampal-EC system contributes to well-known age-related deficits in spatial cognition. Aim 3 will use a battery of cutting-edge neuroimaging methods and psychological measures. The researchers will test the hypothesis that navigation deficits can be understood through a functional network-level perspective of how routes become integrated into map-like memory, how people perceive and update spatial knowledge, and how individual, age-related differences in such knowledge influence navigational strategies. Collectively, this body of work will 1) test fundamental predictions about how space and environmental structure are encoded in the human brain, and 2) establish a deep mechanism-level understanding of the marked changes in spatial cognition that occur in aging, mild cognitive impairment, and Alzheimer’s disease. The insights from these tests are necessary if researchers hope to explain, predict, or ultimately develop interventions that could treat the changes in navigation ability that can come with age.

项目摘要|空间导航对于生存至关重要，内嗅皮层（EC）功能可能对于形成和记住认知图是至关重要的。诺贝尔奖获奖的发现具有网格信号的神经元图环境已引起一类理论，这些理论类似于网格的指标 EC促进目标的空间取向，计划和导航。这些相同的航行能力的缺陷是健康衰老和阿尔茨海默氏症相关痴呆（ADRD）的标志，EC功能障碍是之一阿尔茨海默氏病的最早影响，也与临床前认知下降有关。然而，目前，目的地收敛证明EC对记忆和认知映射至关重要，人类EC如何有助于空间记忆机制的原因很大程度上仍然是理论上的，以及网格样信号的下降（那个已经在衰老中观察到，作为ApoE-ε4载体中阿尔茨海默氏病的临床前生物标志物可以导致衰老和ADRD空间能力下降的贡献仍然非常了解。该提案将利用几种强大的虚拟游动和fMRI范式来解决三个空白在文献中：目标1是了解环境结构如何在人脑中代表。广泛的心理证据表明，环境障碍碎片和扭曲了人们的记忆和空间感。 AIM 1将解决原因 - 测试EC编码空间指标的强有力预测人类用来定义和定位自己在太空中，而障碍会影响人们的空间感通过锚定和塑造EC的空间指标的一部分。 AIM 2是解决EC中的空间信号如何互动与海马，并有助于海马依赖性记忆。据信海马建立生活中各个方面的关系图。拟议的研究将测试这一点，以及网格的理论像EC信号一样，请告知1）我们环境的不同部分如何在海马记忆中隔离，但是还有2）海马如何编码导航经验之间的相似性。目标3是测试神经 - 海马-EC系统如何促进众所周知的年龄相关定义的机械模型认识。 AIM 3将使用一系列尖端的神经影像学方法和心理措施。这研究人员将测试可以通过功能网络级别理解导航定义的假设路线如何整合到类似地图的内存中，人们如何感知和更新空间的观点知识以及这种知识中与年龄相关的差异如何影响导航策略。总体而言，这项工作将1）测试有关空间和环境如何的基本预测结构是在人脑中编码的，2）建立对标记的深度机理水平的理解衰老，轻度认知障碍和阿尔茨海默氏病的空间认知变化。见解如果研究人员希望解释，预测或最终制定干预措施，则必须从这些测试中进行这些测试可以治疗随着年龄的增长的导航能力变化。