EEG Connectivity Signatures in Migraine and Tension-Type Headache: A Multimethod ROI-Based Functional Connectivity and Machine-Learning Analysis.

Background/

Objectives

Migraine and tension-type headache (TTH) are common primary headache disorders, but their underlying network-level EEG patterns remain incompletely characterized. We examined whether resting-state functional connectivity measured with complementary estimators, predefined sensor-level regions of interest (ROIs), graph features, and machine-learning models could distinguish migraine, TTH, and healthy controls.

Methods

The study included 150 participants (61 migraine, 47 TTH, and 42 controls). Connectivity was calculated in the delta, theta, alpha, beta, and gamma bands using coherence, imaginary coherence, weighted phase-lag index (wPLI), and debiased wPLI. We evaluated global, regional, topographic, and graph-theoretical features, performed ROC-AUC analyses, and tested classification models with nested cross-validation. To limit the multiple-testing burden, false discovery rate correction was applied to a prespecified, hypothesis-driven ROI set.

Results

Eight candidate ROI features remained significant after correction. TTH showed the highest gamma temporo-parietal coherence, whereas migraine showed higher gamma temporo-parietal wPLI and debiased wPLI and a higher exploratory migraine probability-like score. Controls had higher delta fronto-temporal and gamma fronto-temporal/temporo-parietal imaginary coherence. Single-feature ROC-AUC values were moderate, and the nested machine-learning models showed only modest classification performance.

Conclusions

The results point to method-dependent, region-specific sensor-level EEG differences across migraine, TTH, and control groups. They are best viewed as candidate neurophysiological signatures rather than clinically ready biomarkers. External validation, fuller clinical covariate assessment, and source-level analyses are needed before diagnostic use can be considered. Future studies should also examine whether these candidate signatures differ according to aura status and episodic or chronic headache subtype.