Temporal Lobe Epilepsy Perturbs the Brain‐Wide Excitation‐Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.079 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.002 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".