IMPORTANCE Cortical stimulation is used during presurgical epilepsy evaluation for functional mapping and for defining the cortical area responsible for seizure generation. Despite wide use of cortical stimulation, the association between cortical stimulation-induced seizures and surgical outcome remains unknown.OBJECTIVE To assess whether removal of the seizure-onset zone resulting from cortical stimulation is associated with a good surgical outcome.

For patients with drug-resistant focal epilepsy, surgery is the therapy of choice in order to achieve seizure freedom. Epilepsy surgery foremost requires the identification of the epileptogenic zone (EZ), defined as the brain area indispensable for seizure generation. The current gold standard for identification of the EZ is the seizure-onset zone (SOZ). The fact, however that surgical outcomes are unfavorable in 40–50% of well-selected patients, suggests that the SOZ is a suboptimal biomarker of the EZ, and that new biomarkers resulting in better postsurgical outcomes are needed. Research of recent years suggested that high-frequency oscillations (HFOs) are a promising biomarker of the EZ, with a potential to improve surgical success in patients with drug-resistant epilepsy without the need to record seizures. Nonetheless, in order to establish HFOs as a clinical biomarker, the following issues need to be addressed. First, evidence on HFOs as a clinically relevant biomarker stems predominantly from retrospective assessments with visual marking, leading to problems of reproducibility and reliability. Prospective assessments of the use of HFOs for surgery planning using automatic detection of HFOs are needed in order to determine their clinical value. Second, disentangling physiologic from pathologic HFOs is still an unsolved issue. Considering the appearance and the topographic location of presumed physiologic HFOs could be immanent for the interpretation of HFO findings in a clinical context. Third, recording HFOs non-invasively via scalp electroencephalography (EEG) and magnetoencephalography (MEG) is highly desirable, as it would provide us with the possibility to translate the use of HFOs to the scalp in a large number of patients. This article reviews the literature regarding these three issues. The first part of the article focuses on the clinical value of invasively recorded HFOs in localizing the EZ, the detection of HFOs, as well as their separation from physiologic HFOs. The second part of the article focuses on the current state of the literature regarding non-invasively recorded HFOs with emphasis on findings and technical considerations regarding their localization.

Minimum Norm Estimation (MNE) is an inverse solution method widely used to reconstruct the source time series that underlie magnetoencephalography (MEG) data. MNE addresses the ill-posed nature of MEG source estimation through regularization (e.g., Tikhonov regularization). Selecting the best regularization parameter is a critical step. Generally, once set, it is common practice to keep the same coefficient throughout a study. However, it is yet to be known whether the optimal lambda for spectral power analysis of MEG source data coincides with the optimal regularization for source-level oscillatory coupling analysis. We addressed this question via extensive Monte-Carlo simulations of MEG data, where we generated 21,600 configurations of pairs of coupled sources with varying sizes, signal-to-noise ratio (SNR), and coupling strengths. Then, we searched for the Tikhonov regularization coefficients (lambda) that maximize detection performance for (a) power and (b) coherence. For coherence, the optimal lambda was two orders of magnitude smaller than the best lambda for power. Moreover, we found that the spatial extent of the interacting sources and SNR, but not the extent of coupling, were the main parameters affecting the best choice for lambda. Our findings suggest using less regularization when measuring oscillatory coupling compared to power estimation.