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
Xie et al. (Wed,) studied this question.