Abstract
<title>Abstract</title> <p>BACKGROUND Migraine is increasingly recognized as a network disorder involving distributed structural and functional brain alterations. However, regional changes in the relationship between resting-state activity and white-matter organization remain unclear. We used the structural decoupling index (SDI), a graph signal processing measure of structure–function alignment, to characterize regional coupling alterations in migraine. METHODS After quality control, 108 participants (41 with episodic migraine [EM], 31 with chronic migraine [CM], and 36 healthy controls [HCs]) underwent resting-state functional, diffusion, and T1-weighted MRI. Regional SDI was computed for 246 Brainnetome regions using individual RD-weighted structural graphs. Group differences were tested by age- and sex-adjusted ANCOVA with Benjamini–Hochberg FDR correction. Partial Spearman correlations examined associations between clinical measures and SDI in regions differing between EM and CM, adjusting for age, sex, and migraine subtype. Exploratory classification used class-weighted linear SVMs with repeated nested fivefold cross-validation. PLS regression related the unthresholded migraine–HC SDI t-map to Allen Human Brain Atlas gene-expression data, followed by enrichment analysis of genes with positive and negative PLS1 weights. RESULTS Compared with HCs, patients with migraine had lower SDI in the left superior frontal gyrus and higher SDI in the right inferior temporal gyrus. Three-group analyses additionally identified differences in the left lateral occipital cortex, where CM showed lower SDI than EM; lower values were associated with more monthly migraine days. Regional SDI features showed preliminary discrimination, strongest for CM versus HCs (AUC = 0.866). Positive PLS1-weighted genes were enriched in chromatin regulation, transcriptional control, and RNA metabolism, whereas negative-weighted genes were enriched in mitochondrial energy metabolism, oxidative phosphorylation, ribosome-associated quality control, and calcium signaling. CONCLUSIONS This first application of SDI to migraine revealed bidirectional hierarchical structure–function disruptions across prefrontal, temporal, and occipital regions. Lower lateral occipital SDI was associated with more monthly migraine days, while regional SDI features showed preliminary within-sample discrimination, strongest for CM versus HCs (AUC = 0.866). Transcriptomic enrichment implicated chromatin regulation and mitochondrial energy metabolism. SDI may provide a useful framework for characterizing hierarchical brain network dysfunction in migraine.</p>