SummaryObjectiveHigh-frequency oscillations (HFOs) are a promising biomarker for the epileptogenic zone. However, no physiological definition of an HFO has been established, so detection relies on the empirical definition of an HFO derived from visual observation. This can bias estimates of HFO features such as amplitude and duration, thereby hindering their utility as biomarkers. Therefore, we set out to develop an algorithm that detects high frequency events in the intracranial EEG that stand out from the background and does not require assumptions about event amplitude or morphology.MethodWe propose the anomaly detection algorithm (ADA), which integrates several unsupervised machine learning techniques to identify segments of data that are distinct from the background. We apply ADA and a standard HFO detector using a root-mean-square amplitude threshold to intracranial EEG from 11 patients undergoing evaluation for epilepsy surgery. The rate, amplitude, and duration of the detected events and the percent overlap between the two detectors are compared.ResultIn the seizure onset zone (SOZ), ADA detected a subset of conventional HFOs. In non-SOZ channels, ADA detected at least twice as many events as the standard approach, including some conventional HFOs; however, ADA also identified many low and intermediate amplitude events missed by the standard amplitude-based method. The rate of ADA events was similar across all channels; however, the amplitude of ADA events was significantly higher in SOZ channels, and the threshold between SOZ and non-SOZ channels was relatively consistent across patients.SignificanceADA does not require human supervision, parameter optimization, or prior assumptions about event shape, amplitude, or duration. It provides an unbiased estimate of HFO features, and our results suggest that amplitude may differentiate SOZ and non-SOZ channels. Further studies will examine the utility of HFO amplitude as a biomarker for epilepsy surgical outcome.