Brain networks are spatiotemporal phenomena that dynamically vary over time. Functional imaging approaches strive to noninvasively estimate these underlying processes. Here, we propose a novel source imaging approach that uses high-density EEG recordings to map brain networks. This approach objectively addresses the long-standing limitations of conventional source imaging techniques, namely, difficulty in objectively estimating the spatial extent, as well as the temporal evolution of underlying brain sources. We validate our approach by directly comparing source imaging results with the intracranial EEG (iEEG) findings and surgical resection outcomes in a cohort of 36 patients with focal epilepsy. To this end, we analyzed a total of 1,027 spikes and 86 seizures. We demonstrate the capability of our approach in imaging both the location and spatial extent of brain networks from noninvasive electrophysiological measurements, specifically for ictal and interictal brain networks. Our approach is a powerful tool for noninvasively investigating large-scale dynamic brain networks.

High-frequency oscillations (HFOs) are a promising biomarker for localizing epileptogenic brain and guiding successful neurosurgery. However, the utility and translation of noninvasive HFOs, although highly desirable, is impeded by the difficulty in differentiating pathological HFOs from nonepileptiform high-frequency activities and localizing the epileptic tissue using noninvasive scalp recordings, which are typically contaminated with high noise levels. Here, we show that the consistent concurrence of HFOs with epileptiform spikes (pHFOs) provides a tractable means to identify pathological HFOs automatically, and this in turn demarks an epileptiform spike subgroup with higher epileptic relevance than the other spikes in a cohort of 25 temporal epilepsy patients (including a total of 2,967 interictal spikes and 1,477 HFO events). We found significant morphological distinctions of HFOs and spikes in the presence/absence of this concurrent status. We also demonstrated that the proposed pHFO source imaging enhanced localization of epileptogenic tissue by 162% (∼5.36 mm) for concordance with surgical resection and by 186% (∼12.48 mm) with seizure-onset zone determined by invasive studies, compared to conventional spike imaging, and demonstrated superior congruence with the surgical outcomes. Strikingly, the performance of spike imaging was selectively boosted by the presence of spikes with pHFOs, especially in patients with multitype spikes. Our findings suggest that concurrent HFOs and spikes reciprocally discriminate pathological activities, providing a translational tool for noninvasive presurgical diagnosis and postsurgical evaluation in vulnerable patients.

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