High-Frequency Hubs of the Ictal Cross-Frequency Coupling Network Predict Surgical Outcome in Epilepsy Patients

Seizure generation is thought to be a process driven by epileptogenic networks; thus, network analysis tools can help determine the efficacy of epilepsy treatment. Studies have suggested that low-frequency (LF) to high-frequency (HF) cross-frequency coupling (CFC) is a useful biomarker for localizing epileptogenic tissues. However, it remains unclear whether the LF or HF coordinated CFC network hubs are more critical in determining the treatment outcome. We hypothesize that HF hubs are primarily responsible for seizure dynamics. Stereo-electroencephalography (SEEG) recordings of 36 seizures from 16 intractable epilepsy patients were analyzed. We propose a new approach to model the temporal-spatial-spectral dynamics of CFC networks. Graph measures are then used to characterize the HF and LF hubs. In the patient group with Engel Class (EC) I outcome, the strength of HF hubs was significantly higher inside the resected regions during the early and middle stages of seizure, while such a significant difference was not observed in the EC III group and only for the early stage in the EC II group. For the LF hubs, a significant difference was identified at the late stage and only in the EC I group. Our findings suggest that HF hubs increase at early and middle stages of the ictal interval while LF hubs increase activity at the late stages. In addition, HF hubs can predict treatment outcomes more precisely, compared to the LF hubs of the CFC network. The proposed method promises to identify more accurate targets for surgical interventions or neuromodulation therapies.