Computational modeling of resistance to hormone-mediated remission in childhood absence epilepsy

Childhood absence epilepsy (CAE) often resolves during adolescence, a period marked by hormonal and neurosteroid changes associated with puberty. However, remission does not occur in all individuals. To investigate this clinical heterogeneity, we developed a simplified thalamocortical model with a layered cortical structure, using deep-layer intrinsically bursting (IB) neurons to represent frontal cortex and regular spiking (RS) neurons modeling the parietal cortex. By simulating two cortical configurations, we explored how variations in neuronal composition and frontocortical connectivity influence seizure dynamics and the effectiveness of allopregnanolone (ALLO) in resolving pathological spike-wave discharges (SWDs) associated with CAE. While both models exhibited similar physiological and pathological oscillations, only the parietal-dominant network (with a higher proportion of RS neurons in layer 5) recovered from SWDs under increased frontocortical connectivity following ALLO administration. These findings suggest that neuronal composition critically modulates ALLO-mediated resolution of SWDs, providing a mechanistic link between structural connectivity and clinical outcomes in CAE, and highlighting the potential for personalized treatment strategies based on underlying network architecture.