Preliminary Quantitative Electroencephalographic Evidence of Depression-Aligned Neurophysiological Patterns in Interictal Migraine: A Multi-Dataset Study

Purpose: This study aimed to examine whether interictal migraine shows neurophysiological patterns aligned with an external major depressive disorder (MDD) reference dataset, using quantitative electroencephalography (qEEG) indices less sensitive to absolute amplifier gain.Methods: Three datasets were analyzed: ds005385 (normative reference, n=608; age-matched subset, 45–70 years, n=309), TDBRAIN (MDD, n=120; insomnia, n=30; healthy controls, n=47), and 25 patients with interictal migraine (chronic migraine, n=7; episodic migraine, n=18; mean age, 60.0 years; female, n=17). Eight candidate qEEG indices were ranked by effect size in TDBRAIN; the aperiodic exponent and frontal-parietal low-beta asymmetry (FP_asym_LowBeta) showed the largest effects and were selected for analysis. Four arousal-state windows were evaluated: eyes-closed resting, hyperventilation, post-hyperventilation 120 seconds, and post-hyperventilation 300 seconds.Results: In TDBRAIN, patients with MDD showed a reduced aperiodic exponent (Cohen’s d=–0.63, p=0.001) and elevated FP_ asym_LowBeta (Cohen’s d=+0.83, p<0.001) versus healthy controls. In migraine, FP_asym_LowBeta was significantly elevated versus the age-matched normative reference after false discovery rate (FDR) correction during hyperventilation (p=0.015), post-hyperventilation 120 seconds (p=0.004), and post-hyperventilation 300 seconds (p=0.003); the eyes-closed resting window showed a nonsignificant trend (p=0.058). Compared with episodic migraine, chronic migraine showed a consistent but exploratory trend toward a lower aperiodic exponent across windows (Cohen’s d=-0.95 to -1.12, using sample-size-weighted pooled standard deviations), though no comparison survived FDR correction. A linear mixed-effects model showed no significant main effect of migraine subtype (p=0.084).Conclusion: Interictal migraine showed preliminary qEEG patterns aligned with those observed in an external MDD reference dataset, particularly in frontal-parietal low-beta asymmetry during hyperventilation and recovery. However, these exploratory findings require validation in larger, age-matched cohorts with appropriate control for medication use and mood-related confounders.