Modeling the Influence of Circadian Rhythm on Ionic Dynamics and the Effect of Antiepileptic Drugs

Abstract

This study examines the interaction between circadian rhythms and the cellular mechanisms underlying epileptic seizures by introducing a circadian modulation into the Epileptor-2 model. A time-dependent factor was implemented to reproduce daily fluctuations in neuronal excitability and seizure occurrence, and its interaction with pharmacological treatments was modeled. The pharmacokinetics of antiepileptic drugs were incorporated to evaluate the effects of dose adjustments and administration schedules aligned with circadian rhythm. Simulations show that including circadian fluctuations in ionic dynamics modifies neuronal excitability and seizure onset and that optimizing dose timing to periods of highest susceptibility can enhance treatment efficacy and reduce seizure risk. These results provide a mechanistic link between ionic-level dynamics and macroscopic biological rhythms and support the potential of personalized chronotherapy for improving epilepsy management.