Abstracts

Rationale: High-frequency oscillations (HFOs), divided into ripples (80-250 Hz) and fast ripples (250-500 Hz), are a promising biomarker for the epileptogenic zone. Presently, it is not clear how to differentiate physiological HFOs from pathological HFOs. This issue is important, but not easy to address, as rates of ripples vary substantially across different brain regions. Physiological HFOs are reported most frequently in the paracentral areas, the hippocampus and the occipital cortex. This multicenter project aimed to investigate normative values for HFO rates across the brain. Methods: Intracranial EEG recordings with channels displaying presumably normal physiological activity were selected from three tertiary epilepsy centers. Channels with normal activity were defined as channels localized in normal tissue, located outside the seizure onset zone, having no spikes, and no slow wave anomaly. All contacts were localized in a common stereotactic space, enabling to perform direct comparisons of EEG activity across subjects and to assess the cerebral structure to which each contact belongs. Twenty-minute artifact-free sections from N2/N3 sleep were selected for automatic detection of ripples (80-250 Hz) and fast ripples (> 250 Hz). The ninety-fifth percentiles of HFO rates per minute were calculated for different brain regions. Results: A total of 1196 channels with normal physiological brain activity from 72 patients were analyzed (Figure 1). The mean ripple rate was 2.3/min; the mean 95th percentile of the ripple rate was 8.8/min. The highest 95% percentile rates were recorded in the occipital cortex (lateral occipital: 32.5/min, mesial occipital: 26.5/min), the hippocampus (20.1/min), the precentral gyrus (17.1/min), the planum temporale (16.5/min), the posterior cingulate gyrus (12.6/min), the postcentral gyrus (8.8/min), the fusiform gyrus (8.7/min), the precuneus (8.4/min), and the superior parietal lobule (8.4/min). Between 36 and 91% of all channels in these regions had ripple rates above the mean rate (Figure 2). Fast ripples were analyzed in 614 channels from 40 patients. The mean rate was very low (0.06/min). Only 11/614 channels had fast ripple rates higher than 0.5/min with an average frequency of 288 Hz. The channels with fast ripple rates > 0.5/min were located in the precentral gyrus (4/12 channels), hippocampus (5/25 channels), and mesial occipital lobe (2/15 channels). Conclusions: The development of an atlas for normative values of HFO rates will aid to better separate normal physiological from abnormal pathological HFO rates. Physiological ripples are frequently found in eloquent cortical areas. This has to be taken into consideration when interpreting rates of HFOs for defining the epileptogenic zone. In contrast, physiological fast ripples are very rare, even in eloquent cortical areas. Funding: This work was supported by the Savoy Epilepsy Foundation (Grant to B.F.), the Botterell Powell’s Foundation (grant to B.F.), and the Canadian Institute of Health Research (grant FDN-143208 to J.G.).