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

项目摘要 该项目的重点是开发非侵入性治疗干预措施，以改善人类 由于健康和病理性衰老过程中出现的空间认知能力下降。正常和正常 衰老过程中发生的病理生理过程导致导航困难。这些挑战可能 会让人极度虚弱。导航的核心能力是规划通往目标的路线的能力。而当 用于导航的大脑回路越来越有特点，这是神经表征的本质 目标导向导航的目标比例仍然较低。我们的目标是描述目标的神经表示 导航位置。为了完整地描述这些表示以及它们在老化过程中如何变化， 无论是年轻的还是年长的非人类灵长类动物都会在虚拟现实中运行迷宫，而无线神经记录 是在前额叶皮质进行的。探索目标导向计算的重要工具 人类的导航就是使用虚拟现实。但虚拟和虚拟之间有重要的区别 现实和现实生活导航，以及将虚拟现实中的研究成果推广到现实世界必须 被探索。为了帮助理解如何将这些发现推广到现实世界，我们的目标是 通过构建与虚拟迷宫匹配的现实世界迷宫，直接比较两种情况下的神经活动。 猴子将学会在虚拟现实中迷宫中寻找奖励，然后在现实世界中进行评估 类似物。这一新颖的实验设计将允许直接比较神经元的活动和 在虚拟迷宫中学习，在现实世界迷宫中活动和行为。最后，为了刺激 开发治疗方法来解决与年龄相关的空间认知能力下降的祸害，我们将 利用非侵入性重复经颅磁刺激，已经被批准用于治疗重症 抑郁障碍，以刺激幼年和老年猴子前额叶皮质的活动。我们 将研究这种干预如何改变猴子跑迷宫时的神经活动和行为。 我们预计，我们将能够利用这种方法来挽救观察到的老年猴子的导航缺陷。 干预，从而潜在地推进了一条治疗空间认知能力下降的新途径 老年人。

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.