---
title: "Forward reactivation in hippocampal CA1 drives repetition learning and persists with age"
id: "biorxiv-23-forward-reactivation-in-human-hippocampal-ca1-supports-repetition-learning-and"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-23-forward-reactivation-in-human-hippocampal-ca1-supports-repetition-learning-and"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Forward reactivation in hippocampal CA1 drives repetition learning and persists with age
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-23-forward-reactivation-in-human-hippocampal-ca1-supports-repetition-learning-and
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators used high-resolution functional MRI and representational similarity analysis to track hippocampal representations during repeated encoding of two fixed sequences of face–name pairs. - The cohort included 418 participants across a lifespan range (ages 36–100); the source reported that each sequence was encoded twice but did not report additional task timing or trial counts. - Data indicated that during repeated encoding, hippocampal subfields **CA1** and **CA2/3/DG** spontaneously reactivated representations that anticipated the immediate next state in the sequence, without explicit prompting. - Reactivation had a directional component: forward (prospective) reactivation was observed, while backward reactivation was not linked to learning gains. - Forward reactivation in these subfields predicted repetition-related memory improvements; the source reported that only **CA1** forward reactivation remained predictive after accounting for reactivation in other medial temporal lobe regions. - The study team observed no detectable age dependence in forward reactivation effects, suggesting preservation of this mechanism across midlife and older adults. - The authors presented these findings as evidence that repetition learning reflects an active, temporally local prospective computation in the hippocampus, with a distinctive contribution from **hippocampal CA1**. - The manuscript is a preprint and has not undergone peer review; the source did not report detailed methods for fMRI acquisition parameters, exact representational similarity metrics, or behavioral effect sizes in the abstract. - Authors declared no competing interests; supplementary material and full methods are available in the source but were not summarized in the abstract.
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Zhiyao Gao 1 Stanford University School of Medicine; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Zhiyao%2BGao%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Gao%20Z&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AZhiyao%2BGao%2B) * [ORCID record for Zhiyao Gao](http://orcid.org/0000-0002-8909-8096 "Open in new tab") * For correspondence: zhiyao.gao@gmail.com Li Zheng 2 The University of Arizona; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Li%2BZheng%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Zheng%20L&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ALi%2BZheng%2B) Vinod Menon 3 Stanford University * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Vinod%2BMenon%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Menon%20V&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AVinod%2BMenon%2B) Weidong Cai 3 Stanford University * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Weidong%2BCai%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Cai%20W&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AWeidong%2BCai%2B) * [ORCID record for Weidong Cai](http://orcid.org/0000-0001-9581-7774 "Open in new tab") * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5899272/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5899272/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5899272/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5899272/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5899272/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Repetition is a fundamental mechanism for strengthening episodic memory, yet the neural computations engaged during re-exposure remain disputed. Competing accounts attribute repetition-related gains either to retrospective reinstatement of prior events or to the prospective use of learned structure to anticipate what comes next. Using high-resolution functional MRI and representational similarity analysis in a lifespan cohort (N = 418, ages 36 -100), we tracked hippocampal representations as participants twice encoded two fixed sequences of face-name pairs, resolving reactivation by direction, distance and sequence. During repeated encoding, CA1 and CA2/3/DG representations spontaneously anticipated immediate next states, unprompted by explicit task demands. Forward, but not backward, reactivation predicted repetition-related gains, and showed no detectable age dependence. Only CA1 forward reactivation predicted memory gains after accounting for reactivation in other medial temporal lobe regions. Repetition learning is thus an active, temporally local prospective computation with a distinctive CA1 contribution that appears preserved well into old age. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC 4.0 International license](http://creativecommons.org/licenses/by-nc/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/24/2026.10.20.760541.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.20.760541v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Forward reactivation in human hippocampal CA1 supports repetition learning and is preserved in the aging brain Zhiyao Gao, Li Zheng, Vinod Menon, Weidong Cai bioRxiv 2026.10.20.760541; doi: https://doi.org/10.64898/2026.10.20.760541 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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