Computational Modeling of Resistance to Hormone-Mediated Remission in Childhood Absence Epilepsy

Childhood absence epilepsy (CAE) is a pediatric generalized epilepsy disorder characterized by brief episodes of impaired consciousness and distinctive 2.5--5 Hz spike-wave discharges (SWDs) on electroencephalography. Although CAE often remits spontaneously during adolescence, the mechanisms driving remission remain poorly understood to effectively guide early intervention practices. Progesterone and its neuroactive metabolite allopregnanolone (ALLO) have been implicated in modulating absence seizure activity. Using a conductance-based thalamocortical model, we previously demonstrated that ALLO enhances GABAa receptor-mediated inhibition, resolving SWDs and supporting the hypothesis that pubertal hormonal shifts may facilitate remission. However, not all patients experience remission despite similar hormonal changes. To investigate mechanisms of resistance to ALLO-mediated remission, we developed an enhanced thalamocortical model that incorporates a layered cortical structure to examine regional cortical heterogeneity and frontocortical connectivity. Our results suggest that non-resolving CAE may result not only from increased frontocortical connectivity but also from the underlying cellular composition of the network. In particular, a higher proportion of bursting-type neurons may prevent the therapeutic effects of allopregnanolone. This work highlights the role of network-level properties in influencing disease outcomes and demonstrates the utility of computational modelling in exploring divergent disease trajectories where empirical models remain limited.

Computational Modeling of Resistance to Hormone-Mediated Remission in Childhood Absence Epilepsy

Monday, July 14 at 6:00pm

Maliha Ahmed

"Computational Modeling of Resistance to Hormone-Mediated Remission in Childhood Absence Epilepsy"

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