Optimization of surgical intervention outside the epileptogenic zone in the Virtual Epileptic Patient (VEP)

Studies to improve the efficacy of epilepsy surgery have focused on better refining the localization of the epileptogenic zone (EZ) with the aim of effectively resecting it. However, in a considerable number of patients, EZs are distributed across multiple brain regions and may involve eloquent areas that cannot be removed due to the risk of neurological complications. There is a clear need for developing alternative approaches to induce seizure relief, but minimal impact on normal brain functions. Here, we develop a personalized in-silico network approach, that suggests effective and safe surgical interventions for each patient. Based on the clinically identified EZ, we employ modularity analysis to identify target brain regions and fiber tracts involved in seizure propagation. We then construct and simulate a patient-specific brain network model comprising phenomenological neural mass models at the nodes, and patient-specific structural brain connectivity using the neuroinformatics platform The Virtual Brain (TVB), in order to evaluate effectiveness and safety of the target zones (TZs). In particular, we assess safety via electrical stimulation for pre- and post-surgical condition to quantify the impact on the signal transmission properties of the network. We demonstrate the existence of a large repertoire of efficient surgical interventions resulting in reduction of degree of seizure spread, but only a small subset of them proves safe. The identification of novel surgical interventions through modularity analysis and brain network simulations may provide exciting solutions to the treatment of inoperable epilepsies. Author summary We propose a personalized in-silico surgical approach able to suggest effective and safe surgical options for each epilepsy patient. In particular, we focus on deriving effective alternative methods for those cases where EZs are inoperable because of issues related with neurological complications. Based on modularity analysis using structural brain connectivity from each patient, TZs that would be considered as surgical sites are obtained. The acquired TZs are evaluated by personalized brain network simulations in terms of effectiveness and safety. Through the feedback approach combining modularity analysis and brain network simulations, the optimized TZ options that minimize seizure propagation while not affecting normal brain functions are obtained. Our study has a great importance in that it demonstrates the possibility of computational neuroscience field being able to construct a paradigm for personalized medicine by deriving innovative surgical options suitable for each patient and predicting the surgical outcomes.