Progress and remaining challenges in the application of high frequency oscillations as biomarkers of epileptic brain

High-frequency oscillations (HFOs: 30–2000 Hz) have been proposed as biomarkers of physiological and pathological brain processes. The majority of the results in human epilepsy have focused on HFOs recorded in the high gamma (65–100 Hz), ripple (100–250 Hz), and fast ripple (250–600 Hz) frequency. 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 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. Here we provide an objective review of the literature and provide data and computer code for detectors in an effort to promote reproducible research and accelerate clinical translation.