Pathological and Physiological High-frequency Oscillations on Electroencephalography in Patients with Epilepsy

High-frequency oscillations (HFOs) encompass ripples (80 Hz-200 Hz) and fast ripples (200 Hz-600 Hz), serving as a promising biomarker for localizing the epileptogenic zone in epilepsy. Spontaneous fast ripples are always pathological, while ripples may be physiological or pathological. Distinguishing physiological from pathological ripples is important not only for designating epileptogenic brain regions, but also for investigations that study ripples in the context of memory encoding, consolidation, and recall in patients with epilepsy. Many studies have sought to identify distinguishing features between pathological and physiological ripples over the past two decades. Physiological and pathological ripples differ with respect to their spatial location, cellular mechanisms, morphology, and coupling with background electroencephalographic activity. Retrospective studies have demonstrated that differentiating between pathological and physiological ripples can improve surgical outcome prediction. In this review, we summarize the characteristics, differences, and applications of pathological and physiological HFOs and discuss strategies for their clinical translation.