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Record W4406382082 · doi:10.1002/advs.202406835

Temporal Lobe Epilepsy Perturbs the Brain‐Wide Excitation‐Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction

2025· article· en· W4406382082 on OpenAlexafffund
Ke Xie, Jessica Royer, Raúl Rodríguez‐Cruces, Linda Horwood, Alexander Ngo, Thaera Arafat, Hans Auer, Ella Sahlas, Judy Chen, Yigu Zhou, Sofie L. Valk, Seok‐Jun Hong, Birgit Frauscher, Raluca Pana, Andrea Bernasconi, Neda Bernasconi, Luis Concha, Boris C. Bernhardt

Bibliographic record

VenueAdvanced Science · 2025
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersFonds de Recherche du Québec - SantéConsejo Nacional de Ciencia y TecnologíaInstitute for Basic ScienceHospital for Sick ChildrenCanadian Institutes of Health ResearchChina Scholarship CouncilNational Research Foundation of KoreaNational Research FoundationCanada Research ChairsDirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de MéxicoNatural Sciences and Engineering Research Council of CanadaFondation Brain Canada
KeywordsEpilepsyNeuroscienceTemporal lobeCognitionBalance (ability)MedicinePsychology

Abstract

fetched live from OpenAlex

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models. A broad decrease in the Hurst exponent is observed in pharmaco-resistant temporal lobe epilepsy (TLE), suggesting more excitable network dynamics. Connectome decoders point to temporolimbic and frontocentral cortices as plausible network epicenters of E/I imbalance. Furthermore, computational simulations reveal that enhancing cortical excitability in TLE reflects atypical increases in recurrent connection strength of local neuronal ensembles. Mixed cross-sectional and longitudinal analyses show stronger E/I ratio elevation in patients with longer disease duration, more frequent electroclinical seizures as well as interictal epileptic spikes, and worse cognitive functioning. Hurst exponent-informed classifiers discriminate patients from healthy controls with high accuracy (72.4% [57.5%-82.5%]). Replicated in an independent dataset, this work provides in vivo evidence of a macroscale shift in E/I balance in TLE patients and points to progressive functional imbalances that relate to cognitive decline.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
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 head0.023
GPT teacher head0.298
Teacher spread0.275 · 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 designObservational
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

Citations22
Published2025
Admission routes2
Has abstractyes

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