Modulation of human intracranial theta oscillations during freely moving spatial navigation and memory

Abstract

How the human brain supports accurate navigation of a learned environment has been an active topic of research for nearly a century1-5. In rodents, the theta rhythm within the medial temporal lobe (MTL) has been proposed as a neural basis for fragmenting incoming information and temporally organizing experiences and is thus widely implicated in spatial and episodic memory6. In addition, high-frequency theta (~8Hz) is associated with navigation, and loss of theta results in spatial memory deficits in rats 7. Recently, high-frequency theta oscillations during ambulatory movement have been identified in humans8,9, though their relationship to spatial memory remains unexplored. Here, we were able to record MTL activity during spatial memory and navigation in freely moving humans immersed in a room-scale virtual reality (VR) environment. Naturalistic movements were captured using motion tracking combined with wireless VR in participants implanted with an intracranial electroencephalographic (iEEG) recording system for the treatment of epilepsy. We found that prevalence of theta oscillations across brain sites during both learning and recall of spatial locations during ambulatory navigation is critically linked to memory performance. This finding supports the reinstatement hypothesis of episodic memory--thought to underlie our ability to recreate a prior experience10-12--and suggests that theta prevalence within the MTL may act as a potential representational state for memory reinstatement during spatial navigation. Additionally, we found that theta power is hexadirectionally modulated13-15 as a function of the direction of physical movement, most prominently after learning has occurred. This effect bears a resemblance to the rodent grid cell system16 and suggests an analog in human navigation. Taken together, our results provide the first characterization of neural oscillations in the human MTL during ambulatory spatial memory tasks and provide a platform for future investigations of neural mechanisms underlying freely moving navigation in humans.