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-IFCN-H (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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Stokes, Jared; Kyle, Colin; Ekstrom, Arne D (2015) Complementary roles of human hippocampal subfields in differentiation and integration of spatial context. J Cogn Neurosci 27:546-59
Watrous, Andrew J; Fell, Juergen; Ekstrom, Arne D et al. (2015) More than spikes: common oscillatory mechanisms for content specific neural representations during perception and memory. Curr Opin Neurobiol 31:33-9
Kyle, Colin T; Smuda, Dana N; Hassan, Abdul S et al. (2015) Roles of human hippocampal subfields in retrieval of spatial and temporal context. Behav Brain Res 278:549-58
Schedlbauer, Amber M; Copara, Milagros S; Watrous, Andrew J et al. (2014) Multiple interacting brain areas underlie successful spatiotemporal memory retrieval in humans. Sci Rep 4:6431
Copara, Milagros S; Hassan, Abdul S; Kyle, Colin T et al. (2014) Complementary roles of human hippocampal subregions during retrieval of spatiotemporal context. J Neurosci 34:6834-42
Watrous, Andrew J; Ekstrom, Arne D (2014) The spectro-contextual encoding and retrieval theory of episodic memory. Front Hum Neurosci 8:75
Ekstrom, Arne D (2014) Cognitive neuroscience: navigating human verbal memory. Curr Biol 24:R167-8
Ekstrom, Arne D; Watrous, Andrew J (2014) Multifaceted roles for low-frequency oscillations in bottom-up and top-down processing during navigation and memory. Neuroimage 85 Pt 2:667-77
Zhang, Hui; Zherdeva, Ksenia; Ekstrom, Arne D (2014) Different "routes" to a cognitive map: dissociable forms of spatial knowledge derived from route and cartographic map learning. Mem Cognit 42:1106-17
Watrous, Andrew J; Lee, Darrin J; Izadi, Ali et al. (2013) A comparative study of human and rat hippocampal low-frequency oscillations during spatial navigation. Hippocampus 23:656-61

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