Influences of Environmental Geometry and Aging on Cognitive Mapping Mechanisms

项目摘要|空间导航是生存的基础，内嗅皮质（EC）功能可能 是形成和记忆认知地图的基础。获得诺贝尔奖的发现是， 神经元用网格状信号映射环境已经产生了一类理论， 电子商务促进空间定位，规划和导航的目标。这些导航能力的缺陷 是健康老龄化和阿尔茨海默病相关痴呆（ADRD）的标志，EC功能障碍是其中之一。 阿尔茨海默病的早期影响，并与临床前认知能力下降有关。然而，在这方面， 在这个时候，尽管有一致的证据表明EC是记忆和认知映射的中心，但人类的EC是如何形成的？ 对空间记忆机制的贡献在很大程度上仍然是理论上的，以及网格状信号如何下降（ 已在衰老中观察到，并作为APOE-ε4携带者中阿尔茨海默病的临床前生物标志物）， 导致衰老中空间能力的下降，ADRD仍然知之甚少。 这项提案将利用几个强大的虚拟导航和功能磁共振成像范例来解决三个差距 目的1是了解环境的结构是如何在人脑中表示的。 大量的心理学证据表明，环境障碍会破坏和扭曲人们的 记忆和空间感。目标1将解决为什么-测试EC编码空间度量的强预测 人类用来在空间中定位和定位自己，而障碍物塑造了人们的空间感， 部分通过锚定和塑造来自EC的空间度量。目的2是解决EC中的空间信号如何相互作用 与海马体相连，并有助于海马体依赖性记忆。据信海马体 构建我们生活不同方面的关系图。拟议中的研究将测试这一点，以及网格理论- 就像EC信号告知1）我们环境的不同部分如何在海马记忆中被隔离， 2）海马体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系统如何导致众所周知的与年龄相关的空间缺陷的机制模型 认知.目标3将使用一系列尖端的神经成像方法和心理测量。的 研究人员将测试导航缺陷可以通过功能网络水平来理解的假设。 路线如何整合到地图般的记忆中，人们如何感知和更新空间 知识，以及如何个人，年龄相关的差异，这些知识的影响导航策略。 总的来说，这一系列工作将1）测试关于空间和环境如何变化的基本预测。 结构在人脑中编码，2）建立对标记的深层机制水平的理解 在空间认知的变化，发生在老化，轻度认知障碍，和阿尔茨海默氏病。的见解 如果研究人员希望解释、预测或最终开发出 可以治疗随着年龄增长而出现的导航能力的变化。

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.