Precursors of seizures due to specific spatial-temporal modifications of evolving large-scale epileptic brain networks

Knowing when, where, and how seizures are initiated in large-scale epileptic brain networks remains a widely unsolved problem. Seizure precursors – changes in brain dynamics predictive of an impending seizure – can now be identified well ahead of clinical manifestations, but either the seizure onset zone or remote brain areas are reported as network nodes from which seizure precursors emerge. We aimed to shed more light on the role of constituents of evolving epileptic networks that recurrently transit into and out of seizures. We constructed such networks from more than 3200 hours of continuous intracranial electroencephalograms recorded in 38 patients with medication refractory epilepsy. We succeeded in singling out predictive edges and predictive nodes. Their particular characteristics, namely edge weight respectively node centrality (a fundamental concept of network theory), from the pre-ictal periods of 78 out of 97 seizures differed significantly from the characteristics seen during inter-ictal periods. The vast majority of predictive nodes were connected by most of the predictive edges, but these nodes never played a central role in the evolving epileptic networks. Interestingly, predictive nodes were entirely associated with brain regions deemed unaffected by the focal epileptic process. We propose a network mechanism for a transition into the pre-seizure state, which puts into perspective the role of the seizure onset zone in this transition and highlights the necessity to reassess current concepts for seizure generation and seizure prevention.