Phase-amplitude coupling between low- and high-frequency activities as preoperative biomarker of focal cortical dysplasia subtypes

Objective: To evaluate whether ictal phase-amplitude coupling (PAC) between high-frequency activity and low-frequency activity could be used as a preoperative biomarker of Focal Cortical Dysplasia (FCD) subtypes. We hypothesize that FCD seizures present unique PAC characteristics that may be linked to their specific histopathological features.Methods: We retrospectively examined 12 children with FCD and refractory epilepsy who underwent successful epilepsy surgery. We identified ictal onsets recorded with stereo-EEG. We estimated the strength of PAC between low-frequencies and high-frequencies for each seizure by means of modulation index. Generalized mixed effect models and receiver operating characteristic (ROC) curve analysis were used to test the association between ictal PAC and FCD subtypes.Results: Ictal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ-electrodes (p < 0.005). No differences in ictal PAC were found on non-SOZ electrodes. Pre-ictal PAC reg-istered on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9 (p < 0.05).Conclusions: The correlations between histopathology and neurophysiology provide evidence for the con-tribution of ictal PAC as a preoperative biomarker of FCD subtypes.Significance: Developed into a proper clinical application, such a technique may help improve clinical management and facilitate the prediction of surgical outcome in patients with FCD undergoing stereo -EEG monitoring.(c) 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Automated summary

This study aimed to evaluate whether ictal phase-amplitude coupling (PAC) could be used as a preoperative biomarker for Focal Cortical Dysplasia (FCD) subtypes. It was found that the strength of ictal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ electrodes. Pre-ictal PAC on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9.