CRCNS Research Proposal: US-German Collaboration: Roles of place and grid cells and phase precession in human spatial and episodic memory

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A fundamental issue that affects everyone's life is how the brain represents memories and how this process sometimes experiences dysfunction. To examine this topic, our research project uses direct human brain recordings to characterize the brain signals that represent aspects of individual memories. A key question is understanding how the brain supports tasks such as answering "Where did I leave my keys this morning"? In this project, we will test how memory-related spatial information is represented by the activity of individual cells in the human brain. We perform this work by examining direct human brain recordings, working with patients who are undergoing neurosurgery to map their epilepsy. While the brain signals are recorded, patients play a video game that involves spatial navigation and memory. We measure patterns of electrical activity that show how the brain stores memories for individual spatial locations and well as for events in time. In particular, we focus on measuring the role in memory of a particular cell type, the "grid cell", that is known to play a role in spatial navigation, to test whether the brain's navigation network also supports memory storage. By revealing the neural basis of memory, this work has implications for developing treatments for memory and navigation disorders such as Alzheimer's Disease. In addition to these scientific objectives, there is a direct educational component to our work. Through performing our research, we will train students at various levels, including graduate, undergraduate, and post-doctoral fellows, on the methods used for studying the human brain and its involvement in memory. We also will develop curriculum material for K-12 and undergraduate students to learn about how the brain supports memory and spatial cognition.Scientifically, the goal of this work is characterize the neural basis of episodic memory by identifying how the rate and timing of the activations of human grid and place cells support the storage of spatial memories. By examining these cells' activations as patients perform our hybrid spatial-episodic memory task, we test the broad hypothesis that there is a fundamental link between how the brain represents the location and timing of when events occur. Our main hypothesis is that the activity of grid cells during memory retrieval represents the spatial location where an event occurred. We also test the role of grid cells in memory retrieval based on cues (Aim 1) as well as self-initiated recalls from memory search (Aim 2). Finally, will also evaluate whether temporal ordering of memories is stored via a rhythmic process in the brain, called theta-band phase precession. Our findings are likely to expand our understanding of how the human entorhinal cortex and hippocampus support a range of cognitive and behavioral processes. A companion project is being funded by the Federal Ministry of Education and Research, Germany (BMBF).