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Record W4414095492 · doi:10.1101/2025.09.09.674568

Distinct contributions of hippocampal pathways in learning regularities and exceptions revealed by functional footprints

2025· preprint· en· W4414095492 on OpenAlexafffund
Melisa Gumus, Michael L. Mack

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicMemory and Neural Mechanisms
Canadian institutionsUniversity of Toronto
FundersCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaFondation Brain Canada
KeywordsHippocampal formationFunctional magnetic resonance imagingEntorhinal cortexEncoding (memory)CognitionFootprintHippocampusNeuroimaging

Abstract

fetched live from OpenAlex

Abstract Fundamental aspects of learning are theorized to be supported by hippocampal pathways: monosynaptic pathway (MSP) extracts regularities whereas trisynaptic pathway (TSP) rapidly encodes exceptional items. Yet, the empirical evidence for the dynamic involvement of MSP and TSP in learning remains elusive. We leveraged diffusion-weighted imaging to estimate the end points of MSP- and TSP-related white matter structures (i.e., footprints) within hippocampal subfields and entorhinal cortex. We then measured the activation of pathway-specific footprints with functional magnetic resonance imaging while participants learned novel concepts defined by regularities and exceptions. The functional footprint method revealed links between MSP-related footprint activation and regularity encoding early in learning, and TSP-related footprint activation and exception encoding late in learning. These findings provide novel evidence that learning concept regularities and exceptions is distinctly supported by hippocampal pathways. Pathway footprint approach provides insights into the functional dynamics of the human hippocampus, translating theoretical and computational work into empirically testable questions in humans. Significance Statement Theories suggest that learning involves two main functions of the hippocampus: integrating commonly encountered information and distinctly encoding exceptional items. Yet, the theorized contributions of hippocampal pathways are yet to be empirically validated. We provide the first evidence of this in humans by introducing a multimodal technique (pathway footprints) that targets learning-related activations at the endpoints of hippocampal pathways. The more a pathway is engaged for a given learning experience, the more the pathway endpoints will be activated. This innovation reveals the dynamic involvement of hippocampal pathways in learning: one unites common information early in learning while another encodes exceptional items late in learning. The pathway footprint method offers precise estimates of neural signatures of cognition as refined by anatomy.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.001
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.038
GPT teacher head0.251
Teacher spread0.213 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes2
Has abstractyes

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