The goal of this project is to determine the neural basis of human episodic memory using an innovative combination of high-resolution functional magnetic resonance imaging (fMRI) and intracranial EEG (iEEG). Episodic memory involves knowing where and when an event occurred relative to other events, both of which depend critically on the hippocampus. Yet exactly how and in what manner the hippocampus codes spatial and temporal aspects of episodic memory remains unclear and understudied, particularly in humans where the primary focus of research has been on verbal episodic memory. Using a newly developed experimental paradigm from our lab, we will study the spatial and temporal components of episodic memory, focusing on two critical processes underlying these components: representation and binding. To map these onto the hippocampal circuit, we employ high-resolution fMRI. In contrast to some previous models developed in the rodent, we hypothesize that spatio-temporal representation is a function shared across hippocampal subregions but that subregion CA3/DG plays a distinct role in parsing elements of context to represent an episode. We further hypothesize a central role for hippocampal subregion CA1 in spatio-temporal binding based on its unique connectivity, in contrast to previous models that have focused on CA3/DG. Collaborating with a team of neurologists and neurosurgeons at two different hospitals, we will also employ iEEG in patients undergoing seizure monitoring. This complementary approach will allow us to determine a separate yet critical component of episodic memory: how does coordinated neural activity in the hippocampus, long linked with spatial navigation in the rodent but understudied in humans, underlie representation and binding of spatio-temporal memory? Overall, our proposed experiments will provide novel insight into the neural basis of episodic memory as they take a new approach to this issue paradigmatically and methodologically and allow us to test several different models of hippocampal function, including our model. Neurodegenerative diseases such as stroke, epilepsy, and schizophrenia impact hippocampal subregion function and coordinated neural activity there, often resulting in symptoms of spatial disorientation and temporal confusion in patients afflicted with these conditions. Our approach thus will also have significant implications for neural diseases that affect the hippocampus.

Public Health Relevance

The hippocampus is critical for episodic memory, particularly in coding where and when events occurred. Neurodegenerative diseases such as stroke, epilepsy, and schizophrenia often impact hippocampal function and result in impairments to spatio-temporal episodic memory. Determining how and in what manner the human hippocampus represents space and time will advance our understanding of how damage to this area affects episodic memory.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1 (02))
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Babcock, Debra J
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University of California Davis
Schools of Medicine
United States
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Ekstrom, Arne D; Ranganath, Charan (2018) Space, time, and episodic memory: The hippocampus is all over the cognitive map. Hippocampus 28:680-687
Bouffard, Nichole; Stokes, Jared; Kramer, Hannah J et al. (2018) Temporal encoding strategies result in boosts to final free recall performance comparable to spatial ones. Mem Cognit 46:17-31
Peacock, Candace E; Ekstrom, Arne D (2018) Verbal cues flexibly transform spatial representations in human memory. Memory :1-15
Kolarik, Branden S; Baer, Trevor; Shahlaie, Kiarash et al. (2018) Close but no cigar: Spatial precision deficits following medial temporal lobe lesions provide novel insight into theoretical models of navigation and memory. Hippocampus 28:31-41
Isham, Eve A; Le, Cong-Huy; Ekstrom, Arne D (2018) Rightward and leftward biases in temporal reproduction of objects represented in central and peripheral spaces. Neurobiol Learn Mem 153:71-78
Kyle, Colin T; Stokes, Jared; Bennett, Jeffrey et al. (2017) Cytoarchitectonically-driven MRI atlas of nonhuman primate hippocampus: Preservation of subfield volumes in aging. Hippocampus :
Ekstrom, Arne D; Isham, Eve A (2017) Human spatial navigation: Representations across dimensions and scales. Curr Opin Behav Sci 17:84-89
Wisse, Laura E M; Daugherty, Ana M; Olsen, Rosanna K et al. (2017) A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals? Hippocampus 27:3-11
Bohbot, VĂ©ronique D; Copara, Milagros S; Gotman, Jean et al. (2017) Low-frequency theta oscillations in the human hippocampus during real-world and virtual navigation. Nat Commun 8:14415
Arnold, Aiden E G F; Iaria, Giuseppe; Ekstrom, Arne D (2016) Mental simulation of routes during navigation involves adaptive temporal compression. Cognition 157:14-23

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