The goal of this project is to determine the neural basis of the spatial and temporal components that comprise human episodic memory and navigation. Damage to the human hippocampus results in significant impairments to both episodic memory and navigation yet the commonalities behaviorally and neurally remain unclear. We hypothesize that spatial and temporal contextual representations, which in turn include temporal order and interval, underlie episodic memory and navigation in both partially overlapping and unique manners. To understand how the hippocampus codes spatial and temporal context, Aim 1 focuses on employing high-resolution hippocampal functional magnetic resonance imaging (fMRI) and intracranial encephalography (iEEG) to better understand the specific contributions of the microcircuitry of the human hippocampus. Building on experiments and a model we have developed in the past funding period, we hypothesize that hippocampal subfields CA3/DG play a role in differentiation of spatial vs. temporal context while CA1 plays a role in integrating commonalities across these two different forms of context. High-resolution hippocampal fMRI experiments directly test these ideas by employing a combination of experimental designs to tease apart spatial and temporal processing coupled with multivariate pattern analyses (MVPA) to map hippocampal distributed codes for these behavioral components. Hippocampal iEEG experiments focus on understanding how low- frequencies oscillations code both spatial distance and temporal contexts, particularly temporal intervals, which we hypothesize relates primarily to differences in the frequencies of oscillations.
Aim 2 provides a more ?macro? perspective on human episodic memory and navigation, with a focus on the unique cortical-hippocampal and cortical-cortical networks that comprise spatial vs. temporal (order and interval) contextual processing. Building on experiments and a model we have developed over the past funding period, we will employ both whole brain fMRI and multilobular iEEG recordings in patients undergoing seizure monitoring to determine the unique cortical contributions to spatial vs. temporal context. We hypothesize that unique configurations of networks and frequencies of interactions, such as prefrontal-hippocampal interactions for temporal context and parietal-retrosplenial-hippocampal interactions for spatial context, are critical to these representations. Proposed experiments directly test these ideas by again employing both episodic memory and navigation related paradigms. The expected outcomes from this proposal are a better understanding, at both the micro and macro level scale, of how spatial vs. temporal context contribute to human episodic memory and navigation. Specifically, by better understanding the contributions of the hippocampal circuitry to episodic memory and navigation, we can better understand how diseases like stroke and ischemia impact function there. In addition, by delineating the extra-hippocampal cortical contributions, we can better understand and predict compensation following insults to the hippocampus.

Public Health Relevance

The human hippocampus is critical for both episodic memory and navigation, as indicated by the devastating consequences of neural diseases such as stroke and ischemia. Yet, while both episodic memory and navigation rely critically on spatial and temporal processing, we lack an understanding of how the hippocampus and cortical networks contribute to these important dimensions. This proposal seeks to leverage functional magnetic resonance imaging and intracranial electrode recordings in patients to address these gaps in knowledge, with potential outcomes providing 1) a more complete framework for understanding how the hippocampal circuitry underlies memory and navigation 2) how cortical circuits might partially compensate for lost function following hippocampal damage.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Cognition and Perception Study Section (CP)
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Babcock, Debra J
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University of Arizona
Schools of Arts and Sciences
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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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