Role of Prefrontal Cortex in Real World Navigation in Young and Old Primates

前额叶皮层在年轻和年老灵长类动物现实世界导航中的作用

• 批准号: 10288027
• 负责人: MICHAEL L PLATT
• 金额: $ 24.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10288027
• 关键词: Address; Age; Aging; Alzheimer' s Disease; Area; Auditory; Behavior; Brain; Cells; Clinical; Cognition; Color; Computers; Coupled; Development; Dimensions; Discrimination; Elderly; Environment; Exhibits; Experimental Designs; FDA approved; Failure; Goals; Hippocampus (Brain); Human; Impairment; Intervention; Learning; Life; Location; Macaca; Macaca mulatta; Major Depressive Disorder; Maps; Maze Learning; Memory; Mental Depression; Modeling; Monkeys; Mus; Nature; Neurobiology; Neurons; Noise; Paper; Pathology; Pattern; Population; Prefrontal Cortex; Primates; Probability; Process; Rattus; Research; Reversal Learning; Rewards; Rodent; Role; Route; Running; Sampling; Scourge; Shapes; Short-Term Memory; Signal Transduction; Smell Perception; Source; Stress; Techniques; Testing; Therapeutic Intervention; Vision; Wireless Technology; age related; aging brain; analog; behavioral response; clinical development; design; expectation; healthy aging; improved; innovation; neuroimaging; neuroregulation; nonhuman primate; noninvasive brain stimulation; normal aging; novel; pathological aging; relating to nervous system; repetitive transcranial magnetic stimulation; response; senescence; skills; therapy development; tool; virtual; virtual reality

Project Summary This project focuses on the development of noninvasive therapeutic interventions in humans to improve spatial cognition due to declines seen during healthy and pathological aging. Both normal and pathophysiological processes that occur in aging result in difficulties navigating. These challenges can be profoundly debilitating. A central capacity in navigation is the ability to plan routes to goals. While the brain circuits for navigation are increasingly well-characterized, the nature of neural representations of goals for goal-directed navigation remain less so. We aim to describe neural representations for goal locations for navigation. In order to fully describe these representations and how they change in aging, both young and old nonhuman primates will run mazes in virtual reality while wireless neural recordings are performed in the prefrontal cortex. An important tool to explore computations for goal-directed navigation in humans is the use of virtual reality. But there are important differences between virtual reality and real life navigation, and the generalization of findings in virtual reality to the real world must be explored. To aid in understanding how such findings can be extended to the real world, we aim to directly compare neural activity in both contexts by building real world mazes that match virtual ones. Monkeys will learn to navigate a maze for rewards in virtual reality and then assessed in real world analogues. This novel experimental design will allow the direct comparison of neuronal activity and learning in virtual mazes to activity and behavior in real world mazes. Finally, in order to spur the development of therapies to address the scourge of age-related declines in spatial cognition, we will utilize noninvasive repetitive transcranial magnetic stimulation, already approved to treat major depression disorder, to stimulate activity in the prefrontal cortex in both young and old monkeys. We will examine how this intervention changes the neural activity and the behavior as monkeys run mazes. We anticipate that we will be able to rescue observed deficits in navigation in older monkeys using such intervention and hence potentially advance a new path of treatment for declines in spatial cognition in the elderly.

项目摘要 该项目的重点是开发人类的非侵入性治疗干预措施，以改善 由于健康和病理性衰老期间出现的空间认知能力下降。正常和 在衰老中发生的病理生理过程导致导航困难。这些挑战可以 会让人极度虚弱导航的核心能力是规划目标路线的能力。而 导航的大脑回路越来越多地被描述，神经表征的本质 目标导向导航的目标仍然不那么多。我们的目标是描述目标的神经表征 定位导航。为了充分描述这些表征以及它们在衰老过程中的变化， 年轻和年老的非人类灵长类动物都将在虚拟现实中走迷宫， 都是在前额叶皮层进行的探索目标导向计算的重要工具 人类的导航是使用虚拟现实。但是，虚拟和虚拟之间存在着重要的区别， 现实和真实的生活导航，以及将虚拟现实中的发现推广到真实的世界， 被探索。为了帮助理解这些发现如何扩展到真实的世界，我们的目标是 通过建立与虚拟世界相匹配的真实的世界迷宫，直接比较两种情况下的神经活动。 猴子将学习在虚拟现实中通过迷宫获得奖励，然后在真实的世界中进行评估 类似物这种新的实验设计将允许直接比较神经元活动， 从虚拟迷宫中的学习到真实的迷宫中的活动和行为。最后，为了刺激 开发治疗方法，以解决与年龄相关的空间认知下降的祸害，我们将 利用非侵入性重复经颅磁刺激，已被批准用于治疗重大 抑郁症，以刺激年轻和老年猴子的前额叶皮层的活动。我们 将研究这种干预如何改变神经活动和猴子跑迷宫的行为。 我们预计，我们将能够挽救观察到的缺陷，在导航老年猴子使用这样的 因此，有可能为空间认知能力下降的治疗开辟一条新的途径， 老人