Neuronal correlates of avoidance and pursuit during human ambulatory navigation

/ABSTRACT Successfully navigating one’s environment requires simultaneous processing of reward seeking and risk aversion. For example, driving to work or walking through a crowded city center includes reaching spatial targets in a timely manner while avoiding collisions with stationary and/or moving objects. Spatial processing and decisions involving avoidance and pursuit are both linked to medial temporal lobe (MTL) structures including the hippocampus and amygdala, and pathologies within these networks cause altered decision-making patterns. While the physiological aspects of MTL engagement during avoidance and pursuit have been explored in rodents and stationary humans, the parallel neuronal mechanisms in freely-moving humans remain entirely unknown. The proposed study will leverage a unique cross-institutional collaboration, recruiting human participants from a database of epilepsy patients with acute or chronic implants to record single-unit and local field potential activity from key regions such as the hippocampus, amygdala, nucleus accumbens, and prefrontal cortex. The project will also harness cutting-edge wearable technologies, including eye tracking, augmented reality (AR), and motion capture. Participants will engage in a naturalistic navigation task requiring the pursuit of spatial targets to earn monetary rewards, all while maintaining a specified distance from an experimenter who is in constant motion within the environment. The proposed research will identify MTL population oscillatory (Aim 1) and single- neuron (Aim 2) mechanisms supporting avoidance and pursuit in freely-moving humans. This will allow for a comprehensive understanding of naturalistic navigation, including aversion to penalties, pursuit of rewards, tracking the movements of another individual, and the manifestation of behaviors such as freezing. The insights gained from this research have the potential to guide the development of stimulation-based therapeutic interventions targeting emotional regulation disorders and other conditions rooted in MTL-related pathologies. Additionally, the proposed study will pave the way towards understanding the intricacies of human cognitive and neural processes in complex real-world scenarios, fostering a bridge between fundamental neuroscience and practical clinical applications. This project will be conducted under the supervision of Dr. Nanthia Suthana and Dr. Ausaf Bari as part of the UCLA-Caltech Medical Scientist Training Program. Project Number: 1F30MH138086-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Humza Zubair | Institution: UNIVERSITY OF CALIFORNIA LOS ANGELES, LOS ANGELES, CA | Award Amount: $42,228 | Activity Code: F30 | Study Section: Special Emphasis Panel[ZRG1 F01B-K (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11166200