High-frequency oscillations and seizure generation in neocortical epilepsy

TLDR

Neocortical seizures are often poorly localized and widespread at onset, limiting surgical options without focal lesions. The study aims to validate that prolonged high‑frequency bursts predict focal neocortical seizures in larger, continuous recordings. High‑frequency (60–100 Hz) epileptiform oscillations were highly localized to the seizure onset zone, appeared in all six patients, predicted 62 % of seizures up to 20 min before onset, were strongest during slow‑wave sleep, implicating thalamic neuromodulation, and suggest that current EEG practices overlook clinically valuable oscillatory signatures.

Abstract

Neocortical seizures are often poorly localized, explosive and widespread at onset, making them poorly amenable to epilepsy surgery in the absence of associated focal brain lesions. We describe, for the first time in an unselected group of patients with neocortical epilepsy, the finding that high‐frequency (60–100 Hz) epileptiform oscillations are highly localized in the seizure onset zone, both before and temporally removed from seizure onset. These findings were observed in all six patients with neocortical epilepsy out of 23 consecutive patients implanted with intracranial electrodes for pre‐surgical evaluation during the study period. The majority of seizures (62%) in these patients were anticipated by an increase in high‐frequency activity in the 20 min prior to neocortical seizure onset. Contrary to observations in normal brain, high‐frequency activity was strongly modulated by behavioural state, and was maximal during slow‐wave sleep, which may explain the propensity for neocortical onset seizures to begin during sleep. These findings point to an important role for neuromodulatory circuits, probably involving the thalamus, in mechanisms underlying seizure generation in neocortical epilepsy. These findings demonstrate that high‐frequency epileptiform oscillations may prove clinically useful in localizing the seizure onset zone in neocortical epilepsy, for identifying periods of increased probability of seizure onset, and in elucidating mechanisms underlying neocortical ictogenesis. Confirmation that prolonged bursts of high‐frequency activity may predict focal onset neocortical seizures will require prospective validation on continuous, prolonged recordings in a larger number of patients. Importantly, the results show that the dynamic range utilized in current clinical practice for localization of epileptogenic brain largely ignores fundamental oscillations that are signatures of an epileptogenic brain. It may prove that many currently available clinical EEG systems and EEG analysis methods utilize a dynamic range that discards clinically important information.