Seizure Forecasting by High-Frequency Activity (80-170 Hz) in Long-term Continuous Intracranial EEG Recordings

Background and Objectives Reliable seizure forecasting has important implications in epilepsy treatment and improving the quality of lives for people with epilepsy. High-frequency activity (HFA) is a biomarker that has received significant attention over the past 2 decades, but its predictive value in seizure forecasting remains uncertain. This work aimed to determine the utility of HFA in seizure forecasting. Methods We used seizure data and HFA (80-170 Hz) data obtained from long-term, continuous intracranial EEG recordings of patients with drug-resistant epilepsy. Instantaneous rates and phases of HFA cycles were used as features for seizure forecasting. Seizure forecasts based on each individual HFA feature, and with the use of a combined approach, were generated pseudo-prospectively (causally). To compute the instantaneous phases for pseudo-prospective forecasting, real-time phase estimation based on an autoregressive model was used. Features were combined with a weighted average approach. The performance of seizure forecasting was primarily evaluated by the area under the curve (AUC). Results Of 15 studied patients (median recording duration 557 days, median seizures 151), 12 patients with >10 seizures after 100 recording days were included in the pseudo-prospective analysis. The presented real-time phase estimation is feasible and can causally estimate the instantaneous phases of HFA cycles with high accuracy. Pseudo-prospective seizure forecasting based on HFA rates and phases performed significantly better than chance in 11 of 12 patients, although there were patient-specific differences. Combining rate and phase information improved forecasting performance compared to using either feature alone. The combined forecast using the best-performing channel yielded a median AUC of 0.70, a median sensitivity of 0.57, and a median specificity of 0.77. Discussion These findings show that HFA could be useful for seizure forecasting and represent proof of concept for using prior information of patient-specific relationships between HFA and seizures in pseudo-prospective forecasting. Future seizure forecasting algorithms might benefit from the inclusion of HFA, and the real-time phase estimation approach can be extended to other biomarkers. Classification of Evidence This study provides Class IV evidence that HFA (80-170 Hz) in long-term continuous intracranial EEG can be useful to forecast seizures in patients with refractory epilepsy.