Network Fragility for Seizure Genesis in an Acute in vivo Model of Epilepsy

Epilepsy affects over 50 million people worldwide and 30% of patients' seizures are medically refractory. The process of localizing and removing the epileptogenic zone is error-prone and ill-posed in part because we do not understand how epilepsy manifests. It has recently been proposed that the epileptic cortex is fragile in the sense that seizures manifest through small perturbations in the synaptic connections that render the entire cortical network unstable. If the fragility of the cortical network could be computed over a period in which seizure genesis occurs, then it might elucidate network mechanisms correlated to the epileptogenic zone. In this study, we used local field potentials (LFP) from neocortex by implementing an acute model of epilepsy in mice. These recordings were used to develop a dynamical network model that quantifies the fragility of the nodes from LFP epochs of baseline activity, preictal and ictal states. Fragility was quantified by the generation of a linear time-varying model to which we then applied a perturbation to determine the sensitivity of nodes in the network. Spatiotemporal fragility maps showed clear quantifiable changes in the epileptogenic network's properties throughout different states of seizure genesis. We quantified this difference over a baseline, preictal and ictal periods to show that network fragility is modulated in the manifestation of epilepsy.