Dynamic Brain Functional Networks to Investigate Protective Mechanisms Against Epileptic Seizures

Epilepsy research increasingly emphasizes the role of brain network dynamics in understanding seizure generation and propagation. This preliminary study applies novel methods of dynamic functional connectivity (dFC) of brain networks to distinguish the network preceding major seizures (pMS) from the one preceding minor electrical discharges (pMED) in 39 drug-resistant epilepsy patients, who underwent invasive stereo-EEG (SEEG) recordings. dFC was analyzed through meta-state analysis of temporal activation sequence (TAS) complexity and dwell time. Statistical comparisons were performed using non-parametric tests and false discovery rate correction. The results indicate distinct dynamic network organization preceding MED onset (pMED) compared to resting state and pMS, with lower TAS complexity and longer dwell time during pMED compared to the other conditions, particularly in the high-frequency range. These changes mainly involve regions outside the epileptogenic zone (EZ). This preliminary evidence suggests a mechanism of dynamical transition toward a more constrained and stable network state preceding MED onset, suggesting a potential inhibitory mechanism that could contribute to suppress seizure occurrence and spreading. These findings show that the development and application of novel techniques to study complex dynamical networks could offer deeper understanding of the regulatory mechanisms in epileptogenic networks and contribute to develop novel treatments based on targeting such networks' alterations.