Pro-ictal, rather than pre-ictal, brain state marked by global critical slowing and local gamma power increase

The clinical workup during the pre-surgical evaluation for epilepsy relies on the electrophysiological recording of spontaneous seizures. The interval until first seizure occurrence is characterized by an increase in seizure likelihood caused by progressive drug dose decreases, during which the epileptic brain transitions from a state of low to a state of high seizure likelihood, so-called pro-ictal state. This study aimed to identify the dynamic brain changes characteristic of this transition from 386 ten-minute segments of intracranial EEG recordings of 29 patients with drug-refractory temporal lobe epilepsy, explored by stereoelectroencephalography, irregularly sampled between electrode implantation and first seizure. As measures of brain dynamics we studied mean phase coherence and relative power in the gamma frequency band, and autocorrelation function width. We further investigate the interaction of those brain dynamics with various susceptibility factors, such as the rate of interictal spikes and high frequency oscillations, circadian and multi-day cycles, and clinical outcomes. We observed a significant increase in relative gamma power in the epileptogenic zone, and an increase in critical slowing in both the epileptogenic zone as well as in presumably healthy cortex. These brain dynamic changes were linked with increases in spike and high frequency oscillations rate. While brain dynamic changes occurred on the slow time scale - from the beginning to the end of the multi-day interval - they did not change in the short-term during the pre-ictal interval. We thus highlight gamma power and critical slowing indices as markers of pro-ictal (as opposed to pre-ictal) brain states, as well as their potential to track the seizure-related brain mechanisms during the presurgical evaluation of epilepsy patients.