Harmonic patterns embedded in ictal EEG signals in focal epilepsy: new insight into the epileptogenic zone

ABSTRACT Objective Localization of the epileptogenic zone (EZ) requires further refinement. We identified a unique ictal spectral structure, the ‘harmonic pattern’ (H pattern), which potentially serves as a novel biomarker for localizing the EZ. This study aimed to analyze the clinical significance of the H pattern and to explore its underlying waveform features. Methods Seventy patients with drug-resistant focal epilepsy, undergoing stereo-EEG (SEEG) evaluation and surgery, were included. Time-frequency maps (TFM) were generated using Morlet wavelet transform analysis. The H pattern was defined as multiple equidistant, high-density bands with varying frequencies on TFM. The upper quartile was employed to confirm contacts expressing dominant H pattern ( d H pattern). Bispectral analysis and transfer function modeling were employed to assess nonlinear properties and propagation, respectively. The performance of the d H pattern in evaluating the EZ was compared with other ictal biomarkers. Results Regardless of seizure onset patterns, the H pattern commonly occurred during early or late seizure propagation among 57 patients (81.4%). It harbored within specific EEG segments characterized by fast activity and irregular polyspikes. The H pattern often appeared simultaneously across different brain regions at a consistent fundamental frequency, highlighting a crucial stage in seizure propagation characterized by inter-regional synchronization. The d H pattern demonstrated greater nonlinearity compared to the non- d H pattern, as evidenced by bispectral analysis. The waveforms associated with the d H pattern were more stereotyped and showed increased skewness and/or asymmetry. Notably, the complete removal of areas exhibiting the d H pattern, but not high epileptogenicity index (≥0.3) or seizure onset zone, was independently associated with seizure freedom after surgery. Significance The H pattern provides unique insights into ictal neural dynamics. Additionally, it is a novel and alternative approach for measuring the EZ over an extended ictal time window. KEY POINTS The harmonic pattern (H pattern) is commonly present in focal epileptic seizures and can help to improve the accuracy of EZ localization over an extended time window. The H pattern is a spectral signature of waveform skewness or asymmetry. The dominant H pattern reflects a stronger nonlinearity of ictal EEG signals. The H pattern can appear simultaneously in different areas with a consistent fundamental frequency, indicating a key stage of inter-regional synchronization.