Elucidating the representational geometries underlying deductive reasoning, generalization, and flexible response generation.

Cognitive flexibility refers to our capacity to adjust our behavior in response to changes in the environment or in our own internal states. Psychiatric disorders often disrupt these cognitive functions, but little is known about the patterns of activity in the brain that underlie these capacities, impeding the development of effective treatments to target them. The overarching goal of this project is to more clearly elucidate the specific neural activity patterns supporting three examples of cognitive flexibility: switching between sets of rules that guide our behavior in a given situation, making correct decisions in new situations by drawing on past experiences, and learning to rapidly adjust a previously learned rule. In this project, I have developed a behavioral task which can engage each of these behaviors. I will use high- channel count electrophysiological methods to record activity from a brain circuit spanning the hippocampus, prefrontal cortex, and motor output regions while non-human primates perform this task. I will test the hypothesis that specific features of the patterns of activity in these brain regions support each type of cognitive flexibility described above. The results of this project will contribute an important step towards developing more effective treatments for cognitive dysfunction by identifying the specific patterns of activity that support specific cognitive functions and behaviors. This project will provide the additional training I require to position myself to perform cutting-edge research on cognition as an independent investigator. Specifically, through this project I will learn to perform precisely anatomically-targeted, high-channel count electrophysiological recordings from multiple brain regions simultaneously in order to probe brain activity patterns relevant to behavior as they occur in real time, distributed across the brain. I will also develop the necessary expertise to analyze the activity of large populations of neurons in relation to complex behavior. This award is thus critical to attaining my long-term goal of running an independent research lab at an academic medical center, where I will operate a non-human primate electrophysiology lab studying the neural mechanisms of adaptive, flexible behaviors that are disrupted in psychiatric disorders. Project Number: 1K08MH143093-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: George Denfield | Institution: COLUMBIA UNIVERSITY HEALTH SCIENCES, NEW YORK, NY | Award Amount: $194,400 | Activity Code: K08 | Study Section: Special Emphasis Panel[ZRG1 ICN-N (92)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11283055