Noninvasive Localization of High-Frequency Oscillations in Children with Epilepsy: Validation against Intracranial Gold-Standard

Introduction: Patients with medically refractory epilepsy (MRE) need surgical resection of the epileptogenic zone (EZ) to gain seizure-freedom. High-frequency oscillations (HFOs, > 80 Hz) are promising biomarkers of the EZ that are typically localized using intracranial electroencephalography (icEEG). The goal of this study was to localize the cortical generators of HFOs non-invasively using high-density (HD) EEG and magnetoencephalography (MEG) and validate the localization against the gold-standard given by the icEEGdefined HFO-zone. Methods: We analyzed simultaneous HDEEG and MEG data from six children with MRE who underwent icEEG and surgery. We detected interictal HFOs (80-160 Hz) on HD-EEG and MEG separately, using an inhouse automatic detector followed by visual human review, and distinguished between HFOs with and without spikes. We localized the cortical generators of each HFO on HD-EEG or MEG using the wavelet Maximum Entropy on the Mean (wMEM). For the HFOs localized in the brain area covered by icEEG, we estimated the localization error (E _loc ) with respect to the gold-standard, and classified them as either concordant (E _loc ≤15mm) or not. Results: We found that: (i) HD-EEG presented a higher rate of HFOs than MEG (1 vs 0.5 HFOs/min, p=0.031); (ii) HFOs without spikes were more likely to be localized outside the brain regions of interest (i.e. covered by icEEG) than HFOs with spikes; and (iii) both HD-EEG and MEG showed high precision to the gold-standard (92% and 96%). Conclusion: We reported quantitative evidence that HDEEG and MEG can localize the HFO cortical generators with high precision to the icEEG gold-standard in children with MRE, suggesting that they may possibly limit the need for icEEG prior to surgery. We also showed that HFOs with spikes on HD-EEG/MEG are more likely to be epileptogenic than those independent from spikes, which may represent physiological events from normal brain.