Influences of Environmental Geometry and Aging on Cognitive Mapping Mechanisms

项目摘要|空间导航是生存的基础，内嗅皮层(EC)功能可能 是形成和记忆认知地图的基础。诺贝尔奖获得者欧共体发现 神经元用网格状信号映射环境产生了一类理论，网格状度量来自 EC促进空间定位、规划和导航到目标。在这些相同的航行能力上的缺陷 是健康老龄化和阿尔茨海默氏症相关痴呆(ADRD)的标志，EC功能障碍是 阿尔茨海默病的最早影响，也与临床前认知能力下降有关。然而， 此时，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EC是如何 对空间记忆机制的贡献在很大程度上仍然是理论上的，以及网格状信号是如何衰减的(即 在APOE-ε4携带者中观察到的衰老和作为阿尔茨海默病的临床前生物标记物)可以 导致衰老时空间能力下降，对ADRD仍知之甚少。 该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 文献：目标1是了解环境的结构是如何在人脑中表现出来的。 广泛的心理学证据表明，环境障碍分割和扭曲了人们的 记忆和空间感。目标1将解决原因--测试EC编码空间指标的强预测 人类用来在太空中定位和定位自己，这些障碍塑造了人们在太空中的空间感 部分是通过锚定和塑造来自EC的空间指标。目标2是解决EC中的空间信号如何相互作用 与海马体结合，促进海马体依赖记忆。据信，海马体 构建我们生活中不同方面的关系地图。拟议的研究将测试这一点，以及网格- 就像EC信号告诉我们，我们环境的不同部分在海马体记忆中是如何分离的，但是 2)海马体如何编码导航体验之间的相似性。目标3是测试一种神经- 海马-EC系统如何导致众所周知的年龄相关性空间缺陷的机制模型 认知力。AIM 3将使用一系列尖端的神经成像方法和心理测量方法。这个 研究人员将测试这一假设，即导航缺陷可以通过功能网络层面来理解 透视路线如何融入地图般的记忆，人们如何感知和更新空间 知识，以及这些知识中与年龄相关的个体差异如何影响导航策略。 总而言之，这一系列工作将检验有关空间和环境 结构是在人脑中编码的，2)建立了对标记的深层机制层面的理解 在衰老、轻度认知障碍和阿尔茨海默病中发生的空间认知变化。洞察力 如果研究人员希望解释、预测或最终开发干预措施，这些测试是必要的 可以治疗随着年龄增长而出现的导航能力变化。

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.