Project Summary/Abstract Decades of research and clinical observations have established that successful spatial navigation and memory depend on the hippocampus and associated structures in the medial temporal lobe (MTL), including entorhinal, perirhinal and parahippocampal cortices [1, 2]. It is thought that the supporting neuronal mechanisms rely on key oscillatory patterns of activity within the MTL that change dynamically when navigating through an environment [3-10]. However, traditional human neuroimaging methodologies do now allow for recording of MTL oscillatory activity during spatial navigation let alone physical movement. The proposed project will implement a first-of-its- kind platform for wireless deep brain recording and stimulation of MTL oscillatory activity during freely moving behaviors to investigate the relationship between spatial navigation, memory, and oscillatory activity, using intracranial electroencephalographic (iEEG) recordings in participants who are implanted with the Neuropace Responsive Neurostimulator (RNS®) for clinical evaluation and treatment of epilepsy. The RNS device will allow for the stimulation and recording of MTL iEEG activity during virtual reality (VR), augmented reality (AR), and real world (RW) spatial navigation tasks with simultaneous recording full-body and eye position and movement using wearable technologies. Together these studies will have access to 70 rare participants implanted with the RNS system over the project period through an ongoing multi-institutional collaboration among clinical and basic science leaders at UCLA, Stanford, and UCSF. Since our studies address basic questions about the role of oscillations in memory, the results will allow for the bridging of findings between species and lay the scientific foundation for helping future patients with diseases where memory is impaired such as Alzheimer’s disease and epilepsy.

Project Narrative Clinical circumstances that allow for chronic recordings from and stimulation of deep brain areas provide a rare opportunity to investigate neural mechanisms underlying freely moving behaviors in humans. The results from the proposed studies will bring in line major discoveries in rodent physiology with the human medial temporal lobe system underlying spatial navigation and memory. These translational studies will address questions about the relationship between deep brain stimulation, oscillatory activity, spatial navigation, and memory, and help lay the foundation for future treatments for illnesses marked by memory impairment.