21th AIAI 2025, 26 - 29 June 2025, Limassol, Cyprus

Higher-Order Multi-Adaptive Neural Network Modeling of the Role of Epigenetics in Epilepsy

de Rizzo Matteo, Treur Jan

Abstract:

  Epilepsy is a disorder that originates from complex interactions between factors such as genetic, epigenetic, and environment, which result in recurrent, unprovoked seizures that often resist conventional treatments. In this paper, a fifth-order adaptive self-modelling network is introduced to capture the way epigenetic processes (including DNA methylation, histone modifications, and microRNA regulation) can cause a shift in neuronal circuits toward a persistent hyperexcitability, resulting in more frequent seizures. The model focuses on BDNF, LIMK1, and two microRNAs (miR-132 and miR-134), illustrating how the presence of excessive excitatory signals may lock brain net-works into a chronic seizure, a prone state under continued stress. The results of the simulation show that sudden increases in stress can push the system beyond its capacity to maintain normal excitability, leading to seizures that persist even after the stress is not present anymore. In a second simulation, an epigenetic therapy aimed at correcting ab-normal methylation and histone acetylation successfully restores many of the disrupted processes, allowing the network to get closer to its pre-stress baseline. These findings indicate that the therapeutic interventions that target maladaptive epigenetic marks seem sound in theory, offering a framework for predicting seizure outcomes and guiding future research in personalized epilepsy treatment.  

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