Context-based neural representations of space: hippocampal-entorhinal neurophysiology in ambulating humans

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ABSTRACT: Memory decline accompanies numerous neurological and psychiatric diseases. To inform the development of effective therapies, understanding how complex memories are encoded in the hippocampal-entorhinal cortex system (HPC-ERC) is critical. Formation of successful episodic memories (of personal events) requires the integration of information across dimensions including the context of an experience within a spatial environment. The proposed research program will determine how the HPC-ERC system flexibly encodes memories across different spatial environmental contexts using rare invasive neural recordings in humans. Data will be collected from two distinct but complementary groups of participants with implanted electrodes: (1) stationary participants with simultaneous single-unit/local field potential (LFP) recordings from the HPC-ERC and (2) freely moving participants with chronic HPC-ERC iEEG recording electrodes. Participants will perform an ecologically meaningful 3D immersive virtual reality (VR) spatial navigation task, either at the bedside (1) or during free movement (2). Findings will illustrate critical neural mechanisms that underlie representations of space and memory in freely moving humans and how these representations encode contextual changes. Additionally, this proposal will identify the relationship between single-unit and LFP activity in humans in relation to spatial navigation and contextual changes, using 3D VR. Results will advance our understanding of HPC-ERC 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.