Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study.

Introduction: Major depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment. Materials and methods: Twenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week's treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients. Results: There were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS. Conclusion: The decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy.