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

TL;DR

This study identifies a unique EEG pattern during seizures that could improve localization of the brain area causing epilepsy.

Contribution

The study introduces the 'harmonic pattern' as a novel biomarker for identifying the epileptogenic zone in focal epilepsy.

Findings

The harmonic pattern appears in most focal epilepsy seizures and is associated with inter-regional synchronization.

The dominant harmonic pattern shows increased nonlinearity and waveform asymmetry compared to non-dominant patterns.

Surgical removal of areas with the dominant harmonic pattern correlates with seizure freedom after surgery.

Abstract

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.

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 (dH pattern). Bispectral analysis and transfer function modeling were employed to assess nonlinear properties and signal propagation, respectively. The performance of the dH pattern in evaluating the EZ was compared with other ictal biomarkers.

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 dH pattern demonstrated greater nonlinearity compared to the non-dH pattern, as evidenced by bispectral analysis. The waveforms associated with the dH pattern were more stereotyped and showed increased skewness and/or asymmetry. Notably, the complete removal of areas exhibiting the dH pattern, but not high epileptogenicity index (≥ 0.3) or seizure onset zone, was independently associated with seizure freedom after surgery.

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.

The online version contains supplementary material available at 10.1186/s12916-026-04665-7.

1. 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.

2. The H pattern is a spectral signature of waveform skewness or asymmetry. The dominant H pattern reflects a stronger nonlinearity of ictal EEG signals.

3. The H pattern can appear simultaneously in different areas with a consistent fundamental frequency, indicating a key stage of inter-regional synchronization.

The online version contains supplementary material available at 10.1186/s12916-026-04665-7.

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