Human hippocampal oscillations during visuomotor exploration - PROJECT SUMMARY Hippocampal theta is one of the most prominent and well-studied neural oscillations in rodent exploration and memory. In rodents, sustained hippocampal theta (4–7 Hz) and coupled gamma (30–100 Hz) rhythms dominate the exploratory state and spatial memory, organizing and sequencing place information for later use. Yet whether mechanisms supporting rodent navigation apply to human episodic memory has been debated for decades. Unlike in rodents, human “theta” occurs in bouts, ranging between 1–13 Hz. The discrepancy between rodent and human theta may result from differences in recording practices, interspecies differences in hippocampal organization, and exclusion of exploratory visuomotor behavior in previous human experiments. Our goal is to define and test the relationship between human exploratory eye and body movements and hippocampal activity along the long axis, at the single unit and population level. We will examine three possible scenarios: (1) hippocampal theta oscillations occur independently of saccades and saccades reset the phase of ongoing theta, potentially to a different degree in the anterior and posterior segments; (2) hippocampal LFP and associated spiking activity is mainly evoked by saccades; and (3) bouts of internally generated theta waves are induced by saccades under cognitive demands. To test these competing models, we will leverage: 1) high- resolution hippocampal intracranial EEG (iEEG) in surgical patients as they participate in visual exploration while measuring single unit and population-level activity; and 2) chronic hippocampal iEEG recordings (Responsive Neurostimulation System, RNS, NeuroPace Inc) in ambulatory epilepsy patients. Chronic iEEG will be integrated with high-density scalp EEG (hd-EEG), and peripheral accessories that track eye and body movements. We propose the following: Aim 1. Define the neurophysiological mechanisms along the hippocampal long axis during visual exploration in surgical patients with high-resolution iEEG. Aim 2. Define the neurophysiological mechanisms along the long axis during ambulatory exploration in patients with chronic iEEG (RNS, NeuroPace). Our experiments will determine if and how hippocampal “theta” or other mechanisms are influenced by exploratory visuomotor behavior, thus referencing decades of rodent literature. Our proposal is innovative in concept and method because we: 1) measure spontaneous eye and body movements during naturalistic exploration, to resemble rodent navigation; 2) use micro/macro contacts to track hippocampal activity at the single unit and population level along the long axis; and 3) integrate chronic iEEG with scalp hd-EEG, eye- tracking, and peripheral accessories in a mobile setting. Our interdisciplinary team of clinicians, neuroscientists, and engineers in the fields of epilepsy, neuroscience, and vision rehabilitation medicine will advance a mechanistic explanation of human hippocampal neurophysiology relevant to a future U01 proposal investigating the hippocampal-neocortical mechanisms of naturalistic memory behaviors.
