Biology subjects

Miller, T. D.

Publications and source records attributed to Miller, T. D..

3 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2025

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↗

bioRxiv2017

Mind-wandering in people with hippocampal amnesia

Subjective inner experiences, such as mind-wandering, represent the fundaments of human cognition. While the precise function of mind-wandering is still debated, it is increasingly acknowledged to have influence across cognition on processes such as future planning, creative thinking and problem-solving, and even on depressive rumination and other mental health disorders. Recently, there has been important progress in characterizing mind-wandering and identifying the neural networks associated with it. Two prominent features of mind-wandering are mental time travel and visuo-spatial imagery, which are often associated with the hippocampus. People with amnesia arising from selective bilateral hippocampal damage ( hippocampal amnesia) cannot vividly recall events from their past, envision their future or imagine fictitious scenes. This raises the question of whether the hippocampus plays a causal role in mind-wandering and if so, in what way. Leveraging a unique opportunity to shadow people with hippocampal amnesia for several days, we examined, for the first time, what they thought about spontaneously, without direct task demands. We found that they engaged in as much mind-wandering as control participants. However, whereas controls thought flexibly and creatively about the past, present and future, imagining vivid visual scenes, hippocampal amnesia resulted in thoughts primarily about the present comprising verbally-mediated semantic knowledge. These findings expose the hippocampus as a key pillar in the neural architecture of mind-wandering and also reveal its impact beyond memory, placing it at the heart of human mental life.\n\nSignificance statementHumans tend to mind-wander about 30-50% of their waking time. Two prominent features of this pervasive form of thought are mental time travel and visuo-spatial imagery, which are often associated with the hippocampus. To examine whether the hippocampus plays a causal role in mind-wandering, we examined the frequency and phenomenology of mind-wandering in patients with selective bilateral hippocampal damage. We found that they engaged in as much mind-wandering as controls. However, hippocampal damage changed the form and content of mind-wandering from flexible, episodic, and scene-based to abstract, semanticized, and verbal. These findings expose the hippocampus as a key pillar in the neural architecture of mind-wandering and reveal its impact beyond memory, placing it at the heart of our mental life.

neuroscience↗