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Biology subjects

Zandi, M. S.

Publications and source records attributed to Zandi, M. S..

2 recordsLinked to original sources

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

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.

neuroscience↗

Decoding memory dysfunction in hippocampal amnesia

The hippocampus reconstructs past experiences by integrating sensory, perceptual, and conceptual information across a cortico-hippocampal autobiographical memory network (AMN). Here, in 18 human participants with amnesia, we decoded the effects of bilateral focal hippocampal damage on distinct autobiographical representations using representational dissimilarity matrices (RDMs). Hippocampal pathology resulted in: (1) impaired generalised episodic memory retrieval RDM model fit in the left angular gyrus; and, (2) reduced distinct episodic memory RDM model fit and trial-by-trial voxel-representational stability in the right angular gyrus, right orbitofrontal cortex, and right inferior frontal gyrus. RDM model fits and mnemonic stability were predicted by total CA23 volumes. Trial-by-trial retrieval stability within the right orbitofrontal cortex and right inferior frontal gyrus predicted autobiographical memory performance, providing the first direct neural correlate between hippocampal dysfunction, altered mnemonic representations, and amnesia. The results demonstrate that hippocampal-mediated amnesia results from impaired mnemonic representational distinctiveness and stability within the AMN.

neuroscience↗