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Sequential narrative binding by hippocampal CA2/3 sustains lifespan episodic detail retrieval

Miller, T. D.; Zhou, J. H.; Handel, A. E.; Pollak, T. A.; Gowland, P. A.; Antoniades, C. A.; Zandi, M. S.; Rosenthal, C. R.

2026-03-19 neuroscience
10.64898/2026.03.17.712337 bioRxiv
Show abstract

Hippocampal subfield contributions to the structure of episodic memories across the lifespan remain incompletely understood, particularly regarding the mechanisms underlying sustained retrieval of detailed events regardless of age. Here, we show that focal hippocampal damage in 32 individuals with amnesia produces time-invariant loss of episodic content details (event specifics, place, perceptual, and emotional content) across six decades, sparing only early childhood memories and semantic details. Temporal context details showed non-monotonic vulnerability, with maximal deficits in recent memories. Volumetric analyses revealed distinct anterior-posterior functional gradients: anterior hippocampal CA3 predicted retrieval across 11-55+ years, posterior CA3 across 18-55+ years, whereas CA1 predicted only recent memories. Computational linguistic analyses using Sentence-BERT semantic embeddings quantified narrative organisation within remembered events via consecutive-sentence semantic relatedness (local narrative coherence) and overall semantic alignment (global narrative coherence). Hippocampal CA2/3 damage impaired local but not global narrative coherence, with reduced local coherence mediating episodic detail loss. This dissociation demonstrates that CA2/3 mediates sequential narrative binding through mechanisms dissociable from broader narrative operations. Concordant time-invariant deficits across quantitative measures of episodic content and computational-linguistic based measures challenge classical systems consolidation predictions, supporting parallel hippocampal-cortical contributions to lifespan episodic memory.

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