Objective To explore the neuromechanism of trans-auricular vagus nerve stimulation(taVNS) for treatment-resistant depression(TRD) based on functional brain network. Methods Twenty-eight patients with TRD were recruited from the psychiatric clinic or by the advertisement. The patients were treated by taVNS(5 Hz/20 Hz

4-8 mA) at the auricular concha for 30 min

twice daily for 8 weeks. The symptom severity was assessed by 17-Item Hamilton Rating Scale for Depression(HAMD-17

ranging from 0 to 54 points

higher score indicates more severe conditions). Resting state fMRI data of the brain were collected to analyze changes of the regional homogeneity(ReHo)

amplitude of low frequency fluctuation(ALFF) and resting state functional connectivity(rs-FC) before and after 8 weeks' taVNS by using DPARSF toolkit and the correlation between the rs-FC and clinical scale score was analyzed to assess the related brain mechanisms. Results Twenty-four patients finished the clinical study

and 23 patients finished the fMRI tests. After the treatment

the average score of HAMD-17 was significantly decreased(P<0.01)

with the reduction rate being 66.95%; the ALFF and ReHo values of the right insula and putamen

the ReHo values of the right caudate nucleus and thalamus

as well as the rs-FC values of the right insula

left superior frontal gyrus and middle frontal gyrus were all significantly decreased(P<0.05). The reduced ReHo value in the right insular lobe was negatively correlated with the HAMD score reduction(P=0.001

r=-0.633). The rs-FC values of the right insula lobe and the left superior frontal gyrus were significantly negatively correlated with the reduced HAMD score(P=0.012

r=-0.512). Conclusion TaVNS significantly relieves the symptoms of TRD patients

which may be related to its functions in regulating functional changes of the right insular and the left frontal gyrus network

and the limbic area and basal ganglia.