Progress and Remaining Challenges in the Application of High Frequency Oscillations as Biomarkers of Epileptic Brain.

High-frequency oscillations (HFOs: 100 - 600 Hz) have been widely proposed as biomarkers of epileptic brain tissue. In addition, HFOs over a broader range of frequencies spanning 30 - 2000 Hz are potential biomarkers of both physiological and pathological brain processes. The majority of the results from humans with focal epilepsy have focused on HFOs recorded directly from the brain with intracranial EEG (iEEG) in the high gamma (65 - 100 Hz), ripple (100 - 250 Hz), and fast ripple (250 - 600 Hz) frequency ranges. These results are supplemented by reports of HFOs recorded with iEEG in the low gamma (30 - 65Hz) and very high frequency (500 - 2000 Hz) ranges. Visual detection of HFOs is laborious and limited by poor inter-rater agreement; and the need for accurate, reproducible automated HFOs detection is well recognized. In particular, the clinical translation of HFOs as a biomarker of the epileptogenic brain has been limited by the ability to reliably detect and accurately classify HFOs as physiological or pathological. Despite these challenges, there has been significant progress in the field, which is the subject of this review. Furthermore, we provide data and corresponding analytic code in an effort to promote reproducible research and accelerate clinical translation.