Graph Theory Analysis Reveals How Transcutaneous Auricular Vagus Nerve Stimulation Modulates Neural Underpinnings Of Patients With Migraine Without Aura

ObjectiveMigraine without aura（Mwo A）is a chronic central nervous system disorder with frequent attacks,causing heavy financial and emotional stress for patients.Transcutaneous auricular vagus nerve stimulation（taVNS）can reduce the intensity of migraine attacks.The main cause of Mwo A in Traditional Chinese medicine is hepatic depression and fire stagnation.and taVNS could harmonizing the liver and gallbleder whereas its neural mechanism for the treatment remains unclear.In this study,we used graph theory to analyze migraine patients and health controls（HCs）’s resting-state functional MRI data,and investigated the neural mechanisms of taVNS for migraine.Thus,this study can provide evidences of brain imaging basis for taVNS.Methods35 patients with Mwo A and 38 age-and gender-matched HCs were employed,and every patient treated with taVNS for 4 weeks.Using rs-f MRI,functional brain images were acquired in the migraine patients before taVNS treatment（Pre M）,migraine patients after taVNS treatment（Post M）,and HCs.Subsequently,the topology properties were calculated for each group based on a functional template and an anatomical template respectively,and compare the topological differences between Pre M,Post M and HCs.In addition,correlations between changes in topology properties and changes in clinical outcomes were estimated.Finally,the commonality between the results of the two templates is compared to increase the confidence level.ResultsResults indicated that Post M significantly reduced pain intensity,attack frequency and total duration in attacks,and also improved quality of life than Pre M.In the graph theory analysis based on functional template,at the level of global indicators,we found that all three groups（i.e.Pre M,Post M and HCs）have significant small-worldness but without difference between groups.Compared to HCs,both Pre M and Post M have significantly higher assortativity.At the level of nodal indicators,Pre M showed abnormal nodal global efficiency in regions of sensory/somatomotor network and temporal lobe than HCs.In contrast to Pre M,the nodal clustering coefficient and nodal local efficiency of Post M indicated changes in regions of default mode network and temporal lobe.Moreover,change in Quality of life level showed significant correlations with changes in nodal clustering coefficient/nodal local efficiency of middle temporal gyrus.In the graph theory analysis based on anatomical template,as the same as the results of another template,all three groups have significant small-worldness but without difference between groups.Both Pre M and Post M have significantly higher assortativity than HCs.Different from the results of functional template,Pre M significantly exhibited lower network efficiency(E_glob)and longer shortest path length（L_p）compared to HCs.But after taVNS,Post M showed no significant difference in E_glob and L_p compared with HCs.ConclusionFrom the clinical results,taVNS significantly relieved the pain of Mwo A patients.Neural mechanisms of the taVNS treatment in Mwo A patients,at global level,is mainly achieved by improving E_glob and L_p of the patients’functional brain network.At local level,taVNS affects the local information transfer and integration capacity in partial brain regions in the default mode network and the temporal lobe.The crossover results showed that,Mwo A has smaller effects on patients’small-worldness;The assortativity of brain network may be able to distinguish Mwo A patients from HCs.