Journal Article

FZJ-2026-01141

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Temporal Lobe Epilepsy Perturbs the Brain‐Wide Excitation‐Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction

Xie, K. ; Royer, J.FZJ* ; Rodriguez-Cruces, R. ; Horwood, L. ; Ngo, A. ; Arafat, T. ; Auer, H. ; Sahlas, E. ; Chen, J. ; Zhou, Y. ; Valk, S. L.FZJ* ; Hong, S.-J. ; Frauscher, B. ; Pana, R. ; Bernasconi, A. ; Bernasconi, N. ; Concha, L. ; Bernhardt, B. C. (Corresponding author)

2025
Wiley-VCH Weinheim

This record in other databases:      

Please use a persistent id in citations: doi:10.1002/advs.202406835  doi:10.34734/FZJ-2026-01141

Abstract: Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in thepathophysiology of epilepsy, with ample research focusing on elucidating itscellular manifestations. However, few studies investigate E/I imbalance at themacroscale, whole-brain level, and its microcircuit-level mechanisms and clin-ical significance remain incompletely understood. Here, the Hurst exponent,an index of the E/I ratio, is computed from resting-state fMRI time series, andmicrocircuit parameters are simulated using biophysical models. A broad de-crease in the Hurst exponent is observed in pharmaco-resistant temporal lobeepilepsy (TLE), suggesting more excitable network dynamics. Connectome de-coders point to temporolimbic and frontocentral cortices as plausible networkepicenters of E/I imbalance. Furthermore, computational simulations revealthat enhancing cortical excitability in TLE reflects atypical increases in recurrentconnection strength of local neuronal ensembles. Mixed cross-sectional andlongitudinal analyses show stronger E/I ratio elevation in patients with longerdisease duration, more frequent electroclinical seizures as well as interictalepileptic spikes, and worse cognitive functioning. Hurst exponent-informedclassifiers discriminate patients from healthy controls with high accuracy(72.4% [57.5%–82.5%]). Replicated in an independent dataset, this workprovides in vivo evidence of a macroscale shift in E/I balance in TLE patientsand points to progressive functional imbalances that relate to cognitive decline

---

Contributing Institute(s):

1. Gehirn & Verhalten (INM-7)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2025; 2025

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Wiley ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---