Abstracts

Rationale: Temporal lobe epilepsy affects the hippocampus which performs both memory and navigation functions. How these two are linked, particularly during real-world navigation, remains unclear, and understanding this intersection is critical for developing treatments targeting these functions. Here, we explored whether neural signals arising during ambulation in the world (e.g., theta oscillations in hippocampus) could also be elicited via associations in memory, or are instead circumscribed specifically to online navigation. Epilepsy patients with implanted Responsive Neurostimulation (RNS) devices with contacts in hippocampus and medial temporal lobe navigated in the real-world while we recorded from their devices. We paired sensory cues with the periods of navigation and tested whether later cue presentation elicited navigation signals.

Methods: The task consisted of three phases, during which hippocampal local field potentials were recorded continuously using RNS: a music pre-exposure phase, navigation phase, and music post-exposure phase. During the music pre-exposure phase, patients listened to two music samples (A & B). They then completed the navigation phase, in which they physically ambulated when one music clip (A) played and stood still when the other clip (B) played. Hippocampal theta oscillations, a stereotyped neural signature of navigation, should thus become associated specifically and uniquely with clip A. Lastly, during the music post-exposure phase, participants were again exposed to the two clips, without navigation.

To replicate previous findings of navigation-based activity, we first conducted a time-frequency decomposition and a cluster-based permutation analysis to detect the frequencies of significant activity during the periods of real-world navigation, as compared to the periods of immobility. To explore associative reactivation of navigation-related signals, we then analyzed changes in hippocampal activity between pre- and post-music exposure phases via frequency decomposition during song presentation.

Results: As predicted, we found elevated theta activity as patients walked, as compared to when they were standing still, particularly in the right hippocampus. Further in line with our predictions, we found increased theta activity in the hippocampus during subsequent presentation of the navigation-paired song, as compared to the song paired with periods of standing still.

Conclusions: This study provides critical insights into the neural mechanisms supporting real-world navigation in humans. Via this rare data collection opportunity, we found support for emerging evidence of theta oscillations in human navigators. We additionally showed that these neural signals are flexible and can be bound to arbitrary stimuli. These findings represent a significant translation between the decades of animal navigation literature and what little is known of naturalistic navigation in humans, with implications for understanding neuropsychiatric comorbidities in epilepsy and other neurologic disorders.

Funding: Please list any funding that was received in support of this abstract.: National Institutes of Health (NIH) Grant R01MH069456 (to N. B. Turk-Browne); Swebilius Foundation Grant (to I. H. Quraishi); NIH Grant 1F99NS125835-01 (to K. N. Graves).