Impaired brain functional hubs and effective connectivity of striatum-cortical network in migraine without aura: a resting-state fMRI study

Introduction: Migraine without aura (MWoA) is a brain network disorder involving abnormal activity in subcortical and cortical brain regions. However, the functional alteration of key nodes and the flow of information within and between brain network in MWoA remain unclear. Thus, we aim to explore functional and effective connectivity (EC) to investigate relationship between impaired brain connectivity and migraine onsets. Methods: Fifty-three MWoA patients and 51 age- and sex-matched healthy controls (HCs) were enrolled in this study. Degree centrality (DC) analysis was used to measure the whole brain functional connectivity, and the abnormal brain regions found by DC were regarded as seeds to perform Granger causality analysis (GCA) to explore EC. Furthermore, a correlation analysis was conducted to determine the relationship between brain abnormalities and clinical symptoms in MWoA. Results: MWoA patients exhibited decreased DC value in left putamen (PUT.L) and increased DC value in left angular gyrus (ANG.L) in whole brain functional integration compared with HCs. In EC, from subcortex to cortex, we found altered EC values from PUT.L to right superior frontal gyrus, medial, right supramarginal gyrus, right superior frontal gyrus, dorsolateral (SFGdor.R) and postcentral gyrus (PoCG.R), and altered EC from bilateral caudate (CAU) to ANG.L. From cortex to subcortex, we observed altered EC value from SFGdor.R to PUT.L, and from ANG.L to left caudate. Furthermore, we found that the EC value from PUT.L to PoCG.R was inversely correlated with the frequency of headache attack and the EC value from CAU.R to ANG.L was positively correlated with duration of illness in MWoA. Conclusion: Our study validated the hypothesis that the functional and effective connectivity between subcortex and cortex were abnormal in MWoA patients compared with HCs, manifesting as alteration in striatum-cortex network, and the inflow and outflow information in striatum-cortex network were correlated with the frequency of headache attack and duration of illness, which may contribute to clarify neuroimaging mechanism of pain sensory during migraine onset, and the abnormality may be an adjunctive biomarker in evaluating severity of migraine and the efficacy of therapeutic intervention.