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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目概要该项目的重点是开发人类非侵入性治疗干预措施，以改善由于健康和病理衰老过程中出现的下降而导致的空间认知能力。正常和衰老过程中发生的病理生理过程会导致导航困难。这些挑战可以使人极度虚弱。导航的核心能力是规划到达目标的路线的能力。尽管用于导航的大脑回路的特征越来越明确，神经表征的本质目标导向导航的目标仍然较少。我们的目标是描述目标的神经表征导航位置。为了充分描述这些表征以及它们在衰老过程中如何变化，年轻和年老的非人类灵长类动物都会在虚拟现实中运行迷宫，同时进行无线神经记录是在前额皮质进行的。探索目标导向计算的重要工具人类的导航是虚拟现实的使用。但虚拟之间存在重要差异现实和现实生活导航，以及将虚拟现实中的发现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扩展到现实世界，我们的目标是通过构建与虚拟迷宫相匹配的现实世界迷宫，直接比较两种环境中的神经活动。猴子将学习在虚拟现实中穿越迷宫以获得奖励，然后在现实世界中进行评估类似物。这种新颖的实验设计将允许直接比较神经元活动和在虚拟迷宫中学习现实世界迷宫中的活动和行为。最后，为了激励开发治疗方法来解决与年龄相关的空间认知下降的祸害，我们将利用无创重复经颅磁刺激，已被批准用于治疗重大疾病抑郁症，刺激年轻和年老猴子的前额皮质活动。我们将研究这种干预如何改变猴子走迷宫时的神经活动和行为。我们预计，我们将能够使用这种方法来挽救老年猴子中观察到的导航缺陷。干预，从而可能为空间认知下降开辟一条新的治疗途径老年人。