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Record W4413434423 · doi:10.1101/2025.08.20.671301

Disrupting selective persistent activity with electrical stimulation impairs human working memory

2025· preprint· en· W4413434423 on OpenAlexaff
Jonathan Daume, Mar Yebra, Chrystal M. Reed, Ivan Skelin, Yousef Salimpour, Jan Kamiński, Andre Cornejo Marin, William S. Anderson, Taufik A. Valiante, Adam N. Mamelak, Ueli Rutishauser

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldNeuroscience
TopicMemory and Neural Mechanisms
Canadian institutionsKrembil FoundationUniversity of TorontoToronto Western Hospital
FundersDeutsche Akademie der Naturforscher Leopoldina - Nationale Akademie der WissenschaftenCedars-Sinai Medical CenterNational Institute of Neurological Disorders and StrokeJohns Hopkins UniversityNational Science Foundation
KeywordsHippocampal formationNeuroscienceStimulationNeural activityPsychologyCognitive psychologyBrain stimulationWorking memoryCognition

Abstract

fetched live from OpenAlex

Working memory (WM) enables the temporary maintenance and manipulation of information, supporting flexible, goal-directed behavior. While converging evidence suggests that the hippocampus contributes to WM storage, its causal role in WM remains unclear. Here, we combined simultaneous intracranial single-neuron recordings in the hippocampus and several cortical areas with focal electrical stimulation in the human hippocampus to test the causal necessity of hippocampal activity for WM. Thirty patients with implanted hybrid depth electrodes performed a WM task with images as memoranda. Electrical stimulation (2 s, 50 Hz, 1 mA) was delivered to the hippocampus during the maintenance period on a subset of trials. Behaviorally, stimulation impaired WM performance, reducing accuracy and increasing response times. Neuronally, stimulation reduced memoranda-selective persistent activity in hippocampus and ventral temporal cortex (VTC), thereby disrupting content-specific neural representations. The extent of neural disruption was correlated trial-by-trial with impaired WM-related behavior, establishing a causal link between disrupted neural activity and impaired WM. At the population level, stimulation shifted neural trajectories farther from attractor states, consistent with degraded mnemonic fidelity. Together, these data provide causal evidence that persistent activity of individual neurons in hippocampus and VTC supports WM maintenance in humans. Our results demonstrate that perturbing hippocampal dynamics disrupts both single-neuron coding and population-level attractor stability, linking cellular mechanisms to behavior and highlighting hippocampal contributions to WM maintenance.

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)0.000
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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.050
GPT teacher head0.280
Teacher spread0.230 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

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