DESCRIPTION (provided by applicant): Spatial navigation and learning is a critical part of life for humans and animals. Our experiments examine how spatial knowledge is represented by individual cells in the human medial temporal lobe. We test the hypothesis that human navigation is supported by networks of place and grid cells, each of which help encode a person's location in a spatial environment by activating at individual locations and groups of locations, respectively. We probe the functional roles of grid and place cells in human spatial navigation and memory by directly recording the activity of these cells from epilepsy patients performing a computer virtual-navigation task. Specific Aims one and four of our work test whether theories of grid and place cells from animal models are relevant for humans. First, we probe the properties of these cells, and their interactions with neuronal oscillations, by conducting a new experiment that is optimized to reveal the human neural representation of space. We will test whether human place and grid cells are most prominent to the right hemisphere, consistent with the classic finding that human spatial processing is right lateralized. Our second and third Specific Aims probe grid and place cells in more complex navigation tasks. Here we test for new neural coding patterns beyond those found in animals. We will test whether place and grid cells are involved in transferring spatial knowledge between related environments and in representing spatial information in outside of active navigation. Our research studies are likely to yield insights into the neural signals that allow humans to navigate and they also have implications for revealing a broader understanding of human memory.

PUBLIC HEALTH RELEVANCE: The proposed research will elucidate the patterns of single-neuron activity in humans that underlie spatial navigation and learning. By expanding our understanding of how the brain supports spatial navigation and memory, our proposed work will lead to new treatments for patients that become disoriented or forget the layout of spatial environments. This work may also produce new insights into the neural basis of other types of memory beyond spatial cognition, as the same neural systems that underlie navigating and remembering spatial environments are also thought to be involved in non-spatial memory processes.