CA2/3-dependent stability of frontal mnemonic representations predict episodic deficits in human amnesia.

The hippocampus reconstructs past experiences by integrating sensory, perceptual, and conceptual information across a cortico-hippocampal autobiographical memory network. Here, in 18 human participants with amnesia, we decode the effects of bilateral focal hippocampal damage on distinct autobiographical representations using representational dissimilarity matrices (RDMs). Hippocampal pathology results in impaired generalized episodic memory retrieval RDM model fit in the left angular gyrus and in reduced distinct episodic memory RDM model fit in the right inferior frontal gyrus (rIFG), while right angular gyrus (rANG) and right orbitofrontal cortex (rOFC) fall below multiple correction thresholds. Trial-by-trial voxel-representational stability is reduced in the rANG, rIFG, and rOFC. The RDM model fits and mnemonic stability are predicted by total CA2/3 volumes. Trial-by-trial retrieval stability within the rOFC and rIFG predicts episodic memory performance, providing a direct neural correlation between hippocampal dysfunction, altered mnemonic representations, and amnesia.

• Publication year

  2025

• Venue

  Cell Reports

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2025.116527PMID 41217932
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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