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bioRxiv · 10.64898/2026.10.20.760541

Forward reactivation in human hippocampal CA1 supports repetition learning and is preserved in the aging brain

Gao, Z.·Zheng, L.·Menon, V.·Cai, W.
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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.

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Gao, Z., Zheng, L., Menon, V., Cai, W.. 2026-10-24. Forward reactivation in human hippocampal CA1 supports repetition learning and is preserved in the aging brain. https://doi.org/10.64898/2026.10.20.760541

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