Although an impressive amount of evidence has emerged supporting a fundamental role for the hippocampus in declarative memory, the manner in which individual structures within the hippocampus contribute to memory remains a current topic of debate. The central objective of this proposal is to evaluate how differences in circuitry among hippocampal subfields translate to functional differences in support of episodic memory formation. In forming new memories, the hippocampus is thought to separate related input patterns into distinct representations, thereby minimizing interference between similar memory traces. However, findings from neural-network models and animal studies suggest that tension exists within the hippocampus such that some subfields readily contribute to pattern separation, whereas others tend to generalize across similar input patterns. Using high-resolution functional magnetic resonance imaging (fMRI), the proposed research aims to evaluate the degree to which human hippocampal subfields support the formation of non-overlapping vs. shared memory representations in response to similarity manipulations at both the item and inter-item level. Furthermore, to complement this high spatial resolution fMRI approach, local field potentials will be directly recorded from the human hippocampus to better characterize the temporal profile of pattern separation and generalization. Delineating the manner in which hippocampal subfields mediate memory will advance mechanistic accounts of hippocampal function, as well as provide insights into brain regions affected in populations exhibiting pattern separation deficits, such as older adults and individuals with schizophrenia.

Public Health Relevance

Delineating the manner in which hippocampal subfields mediate memory will advance mechanistic accounts of hippocampal function and increase understanding of how distinct memory representations are formed in the human brain. In turn, such findings may serve as a foundation from which researchers can examine anatomical and functional changes in the hippocampus in populations exhibiting deficits in forming distinct memories, such as older adults and individuals with schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F12A-E (20))
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Vogel, Michael W
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Stanford University
Schools of Arts and Sciences
United States
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Carr, Valerie A; Bernstein, Jeffrey D; Favila, Serra E et al. (2017) Individual differences in associative memory among older adults explained by hippocampal subfield structure and function. Proc Natl Acad Sci U S A 114:12075-12080
Yushkevich, Paul A; Amaral, Robert S C; Augustinack, Jean C et al. (2015) Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol. Neuroimage 111:526-41
LaRocque, Karen F; Smith, Mary E; Carr, Valerie A et al. (2013) Global similarity and pattern separation in the human medial temporal lobe predict subsequent memory. J Neurosci 33:5466-74