Circadian Modulation of Excitation-Inhibition Balance Drives Ictal Transitions in a Mechanistic Model of Epileptic Networks

Abstract

Epileptic seizures emerge from pathological synchronization in neuronal networks and are strongly influenced by circadian rhythms. Here, we developed a computational framework to investigate how circadian modulation of excitation/inhibition (E/I) balance shapes transitions from physiological to pathological activity. The model consists of interacting excitatory and inhibitory populations containing varying proportions of impaired neurons with altered intrinsic excitability. Circadian effects were incorporated through modulation of synaptic time constants, mimicking daily fluctuations in E/I dynamics. Network activity was characterized using firing rates and the Spike Time Tiling Coefficient (STTC), enabling simultaneous assessment of excitability and synchrony. Our results show that seizure-like dynamics arise from nonlinear interactions between network composition, neuronal impairment, and synaptic kinetics. Distinct dynamic regimes emerged, separated by sharp transitions in synchrony and activity patterns. These findings provide a mechanistic link between circadian regulation and seizure susceptibility, supporting the development of chronotherapy approaches for epilepsy.