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Background Depression is the most common form of mental disorder in community and health care settings and current treatments are far from satisfactory. Vagus nerve stimulation (VNS) is an FDA-approved somatic treatment for treatment-resistant depression. However, the involvement of surgery has limited VNS only to patients who have failed to respond to multiple treatment options. Transcutaneous VNS (tVNS) is a relatively new, non-invasive VNS method based on the rationale that there is afferent / efferent vagus nerve distribution on the surface of the ear. The safe and low-cost characteristics of tVNS have the potential to significantly expand the clinical application of VNS. Methods In this study, we investigated how tVNS can modulate the default mode network (DMN) functional connectivity (FC) in mild or moderate major depressive disorder (MDD) patients. Forty-nine MDD patients were recruited, and received tVNS or sham tVNS (stVNS) treatments. Result 34 patients completed the study and were included in data analysis. After one month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) score reduced significantly in the tVNS group as compared to the stVNS group. The FC between the DMN and anterior insula and parahippocampus decreased; the FC between the DMN and precuneus and orbital prefrontal cortex increased compared to stVNS. All these FC increases are also associated with HAMD reduction. Conclusions tVNS can significantly modulate the DMN FC of MDD patients; our results provide insights to elucidate the brain mechanism of tVNS treatment for MDD patients.

Background Depression presents a significant burden to both patients and society. One treatment that has emerged is vagus nerve stimulation (VNS), an FDA-approved physical treatment for depressive disorders. However, the application of this intervention has been limited by the involvement of surgery and potential side effects. The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD. Methods This is a nonrandomized, controlled study. The first cohort of patients (n = 91) only received transcutaneous auricular VNS (taVNS) for 12 weeks. In the second cohort (n = 69), patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS. All treatments were self-administered by the patients at home after they received training from the hospitals. The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0, 4, 8, and 12. Data analysis included a timelag analysis comparing 1) real and sham taVNS groups at week 4; 2) the real taVNS group at week 4 vs the sham taVNS group at week 8 (fourth week of real taVNS following 4 weeks of sham); and 3) the real taVNS group at week 8 vs the sham taVNS group at week 12 (eighth week of real taVNS following sham). Results After four weeks of treatment, MDD patients in the taVNS group showed greater improvement than that of the sham taVNS group as indicated by both Hamilton score changes as well as response and remission rates at week four. In addition, we also found that the clinical improvements continued until week 12 during taVNS. Limitations Patients were not randomized in this study. Conclusions Our results suggest that taVNS is a promising, safe, and cost-effective therapeutic method for mild and moderate MDD.

Auricular acupuncture has been utilized in the treatment of diseases for thousands of years. Dr. Paul Nogier firstly originated the concept of an inverted fetus map on the external ear. In the present study, the relationship between the auricular acupuncture and the vagal regulation has been reviewed. It has been shown that auricular acupuncture plays a role in vagal activity of autonomic functions of cardiovascular, respiratory, and gastrointestinal systems. Mechanism studies suggested that afferent projections from especially the auricular branch of the vagus nerve (ABVN) to the nucleus of the solitary tract (NTS) form the anatomical basis for the vagal regulation of auricular acupuncture. Therefore, we proposed the “auriculovagal afferent pathway” (AVAP): both the autonomic and the central nervous system could be modified by auricular vagal stimulation via projections from the ABVN to the NTS. Auricular acupuncture is also proposed to prevent neurodegenerative diseases via vagal regulation. There is a controversy on the specificity and the efficacy of auricular acupoints for treating diseases. More clinical RCT trials on auricular acupuncture and experimental studies on the mechanism of auricular acupuncture should be further investigated.

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