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

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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.