bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 27, 2024

A bstract Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with mounting body previous research focusing on elucidating its cellular manifestations. However, there are limited studies into E/I at macroscale and microcircuit-level mechanisms clinical associations. In our current work, we computed Hurst exponent—a previously validated index ratio—from resting-state fMRI time series, simulated microcircuit parameters using biophysical computational models. We found broad reduction exponent pharmaco-resistant temporal lobe epilepsy (TLE), indicative shift towards more excitable network dynamics. Connectome decoders pointed to temporolimbic frontocentral areas plausible epicenters imbalance. Computational simulations further revealed that enhancing cortical excitability patients likely reflected atypical increases recurrent connection strength local neuronal ensembles. Moreover, mixed cross-sectional longitudinal analyses heightened elevation longer disease duration, frequent electroclinical seizures inter-ictal epileptic spikes, worse cognitive functioning. Replicated an independent dataset, work provides compelling in-vivo evidence balance TLE undergoes progressive changes underpins impairments, potentially informing treatment strategies targeting mechanisms.

Language: Английский