High-frequency oscillations in scalp EEG: A systematic review of methodological choices and clinical findings

Objective: Pathological high-frequency oscillations (HFOs) in intracranial EEG are promising biomarkers of epileptogenic tissue, and their physiological counterparts play a role in sensorimotor and cognitive function. HFOs have also been found in scalp EEG, but an overview of all studies is lacking. In this systematic review, we assessed the methodology to detect scalp HFOs and their clinical potential. Methods: We searched PubMed, Embase and the Cochrane Library for studies on HFOs in scalp EEG, and extracted methodological and clinical data. Results: We included 60 studies with data from 1149 unique individuals. Two-thirds of studies analyzed HFOs visually in the time or time–frequency domain, and one-third automatically with visual validation. Most studies evaluated interictal ripples during sleep in children. Pathological HFOs were overall better than spikes in localizing the epileptogenic zone and predicting outcome, correlated negatively with cognition and positively with disease activity and severity, and decreased after medical and surgical treatment. Conclusions: The methodologies of the 60 studies were heterogeneous, but pathological scalp HFOs were clinically valuable as biomarkers in various situations, particularly in children with epilepsy. Significance: This systematic review gives an extensive overview of methodological and clinical data on scalp HFOs, establishing their clinical potential and discussing their limitations.