UCLA

Our ability to recall memories of personal experiences is an essential part of daily life. These episodic memories often involve movement through space and thus require continuous encoding of one’s position relative to the surrounding environment. Formation of successful episodic memories (of personal events) requires the integration of contextual information within a spatial environment. Memory decline accompanies numerous neurological and psychiatric diseases. To inform the development of effective therapies, understanding how complex memories are encoded in the medial temporal lobe (MTL) is critical. To examine how MTL neural representations flexibly encode spatial memories, rare recordings in humans were collected from two complementary cohorts: (1) freely moving participants with chronic intracranial electroencephalographic (iEEG) electrodes and (2) stationary participants with single neuron recording electrodes. All participants completed an ecologically meaningful 3D immersive virtual reality (VR) spatial memory task. Our results highlight the utility of an immersive VR behavioral paradigm to interrogate multi-scale neurophysiology of episodic memory and spatial navigation in humans. We found that MTL theta oscillations dynamically represent memory and spatial variables to support momentary cognitive task demands. Theta oscillations were modulated by (i) memory performance during memory retrieval immediately before conscious recall, (ii) proximity to spatial boundaries or (ii) latently accessed memory representations of previously learned positions. We found that the immersive VR spatial memory paradigm elicited hexadirectional modulation of theta bandpower and also grid cell-like population activity. Interestingly, these hexadirectional modulation spatial representations exhibited putative grid axes reorientation during changing environmental contexts, and preliminary findings suggest that grid cells also may exhibit similar reorientation, suggesting that spatial codes may be context-specific. Altogether, these results demonstrate how human MTL oscillations and single neurons can represent both memory and space in a temporally flexible manner during interactive spatial navigation and memory retrieval. These findings advance our understanding of medial temporal lobe representations of spatial navigation, memory, and the effect of contextual changes that will together serve as a scientific foundation for development of neurological therapies for disorders of memory.