Edge-centric functional diversity alterations and associated transcriptomic profiles of pain and vertigo in the migraine spectrum

Abstract Background The migraine spectrum exhibits substantial clinical heterogeneity, encompassing pain-dominant, vertigo-dominant, and pain-vertigo overlapping manifestations, as represented here by migraine without aura (MwoA), a clinically defined adult vertigo-dominant recurrent vestibular phenotype (hereafter, BPV group), and vestibular migraine (VM), respectively. However, the shared and symptom-preferential functional network alterations and their underlying molecular characteristics across these clinical phenotypes remain poorly understood, hindering individualized precision interventions. Methods Resting-state fMRI data were acquired from 106 patients within the migraine spectrum (16 BPV, 61 MwoA, and 29 VM) and 39 healthy controls (HC). An edge-centric connectome framework was applied to identify overlapping network communities, and regional functional diversity was quantified using normalized entropy. Gene expression profiles and neurotransmitter receptor/transporter maps were integrated to identify molecular patterns spatially associated with aberrant functional diversity. Results All patient groups showed significant functional diversity alterations in the ventral attention network and left precuneus that correlated with symptom severity. MwoA and VM exhibited divergent functional diversity in sensorimotor regions but shared associations with serotonergic maps; BPV and VM shared cerebellar increases associated with gamma-aminobutyric acid type A receptor distribution. VM further exhibited reduced functional diversity in the thalamus and insula, with molecular associations involving genetic homeostasis and glial cell processes. Conclusions Across the migraine spectrum, these distinct clinical phenotypes share network abnormalities related to higher-order attentional regulation, while the pain-containing and vertigo-containing phenotypes exhibit preferential alterations involving pain processing and vestibular regulation, respectively, with the pain-vertigo overlapping phenotype further showing additional abnormalities involving multimodal sensory integration and molecular homeostatic processes. This study delineates shared and symptom-preferential neural signatures across pain-dominant, vertigo-dominant, and pain–vertigo overlapping clinical phenotypes, providing new insights for individualized clinical assessment and precision interventions.