The Circadian Mechanism May Contribute to Vestibular Migraine: A Case-Control Study Based on Resting-State Functional MRI (rs-fMRI)

Abstract Background: Vestibular migraine (VM) pathophysiology remains unclear despite its circadian attack patterns. This study employed resting-state fMRI to characterize brain functional differences in VM patients with distinct diurnal attack rhythms. Methods: Forty-two VM patients (23 with early-morning attacks [VMm]; 19 without [VMnm]) and 19 age-/gender-matched healthy controls (HCs) underwent rs-fMRI. Group differences were analyzed using amplitude of low-frequency fluctuation (ALFF), functional connectivity (FC), graph theory metrics, and clinical correlations. Results: ALFF: Compared to HCs, VMm exhibited decreased ALFF in the left medial orbitofrontal cortex (Frontal_Med_Orb_L) and right medial superior frontal gyrus (Frontal_Sup_Medial_R). VMnm showed reduced ALFF in the right paracentral lobule. VMm had significantly lower orbitofrontal ALFF than VMnm (p<0.05). No group differences emerged in fALFF or ReHo. FC: VMm demonstrated impaired frontal-angular/cingulate connectivity versus HCs, including reduced FC between the right orbital middle frontal gyrus and angular gyrus, and between the right orbital inferior frontal gyrus and anterior cingulate cortex. VMnm exhibited disrupted limbic-temporal networks, with weakened connectivity between the right temporal pole/amygdala, putamen/parahippocampus, and hippocampus/amygdala. VMm showed lower putamen-parahippocampal FC than VMnm. Graph Theory: Global network efficiency (Eg) decreased in both VM groups versus HCs (p<0.05). VMm had reduced betweenness centrality in the left dorsolateral/medial superior frontal gyri and inferior temporal gyrus, while VMnm showed deficits only in the inferior temporal gyrus. Small-world properties (γ, λ, σ) and nodal metrics (degree centrality, clustering coefficient) showed no intergroup differences. Correlations: Left orbitofrontal ALFF negatively correlated with Morningness-Eveningness Questionnaire (MEQ) scores in both VM groups (r=-0.42, p=0.02). Disease duration showed positive but non-significant trends with ALFF values. Conclusions: VM subgroups exhibit distinct interictal functional abnormalities: VMm involves prefrontal dysregulation, while VMnm affects parietal-temporal-limbic integration. The left medial orbitofrontal cortex may serve as a hub regulating VM’s circadian attack rhythms.Reduced global network efficiency reflects impaired left-hemisphere information processing, independent of circadian mechanisms.Persistent fMRI abnormalities during attack-free periods suggest circadian influences on VM pathophysiology, highlighting potential chronotherapeutic targets for prevention and management.