Degenerate time-dependent network dynamics anticipate seizures in human epileptic brain

Epileptic seizures are known to follow specific changes in brain dynamics. While some algorithms can nowadays robustly detect these changes, a clear understanding of the mechanism by which these alterations occur and generate seizures is still lacking. Here, we provide crossvalidated evidence that such changes are initiated by an alteration of physiological network state dynamics. Specifically, our analysis of long intracranial electroencephalography (iEEG) recordings from a group of 10 patients identifies a critical phase of a few hours in which time-dependent network states become less variable ("degenerate"), and this phase is followed by a global functional connectivity reduction before seizure onset. This critical phase is characterized by an abnormal occurrence of highly correlated network instances and is shown to be particularly associated with the activity of the resected regions in patients with validated postsurgical outcome. Our approach characterizes preseizure network dynamics as a cascade of 2 sequential events providing new insights into seizure prediction and control.
Author summary Understanding and predicting the generation of seizures in epileptic patients is fundamental to improving the quality of life of the more than 1% of the world population who suffer from this illness. Although seizure prediction has made important advances over the last decade, there is a lack of understanding of the common principles explaining the transitions that brain activity undergoes before a seizure. In this study, we characterized this transition from a novel perspective grounded on the mathematical analysis of continuous recordings inside the brains of epileptic patients over several days using depth electrodes. We show that the critical period preceding a seizure unfolds in a two-stage process. It begins with a phase of several hours when the highly correlated activity in the preceding days is altered, and it proceeds with a second, shorter phase of decrease in global connectivity before the seizure onset. Furthermore, our analysis reveals that these global alterations are more locally manifested in areas that are selected for surgical treatment. Our study suggests that preseizure activity might follow global stereotyped dynamics that could be targeted and modulated to prevent epileptic seizures.