Alterations of brain activity in right brainstem and right entorhinal cortex mediated anti-depressant effects of transcutaneous auricular vagus nerve stimulation in functional dyspepsia rats: a resting-state fMRI study

Objective: Functional dyspepsia (FD) is often accompanied by depression. Transcutaneous auricular vagus nerve stimulation (taVNS) has been shown beneficial to FD. However, the effect of taVNS on depression is associated with FD and its central mechanism remains unknown. In this study, we investigated depression-like behavioral changes and cerebral alterations of brain activity of taVNS in a rodent model of FD. Methods: Neonatal SD rats were gavaged with iodoacetamide (IA) to induce a FD model. Twenty-one SD rats were randomly divided into control, IA, and taVNS groups (each, n=7). taVNS was performed for 30 minutes once daily for 14 days consecutively. The open field test (OFT) and forced swimming test (FST) were conducted to assess depression-like behaviors. The low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were assessed from resting-state functional magnetic resonance imaging to evaluated the changes of spontaneous neural activity and local neural coordination of FD rats with depression-like behaviors.. Correlations between differential ALFF and ReHo values and depression-like behaviors were analyzed to ascertain taVNS-related central changes. Results: Compared with the control group, the horizontal and vertical scores of OFT were decreased, and the immobility time of FST was increased in the IA group. The ALFF values of the right brainstem were increased in the IA group. The ALFF values of the left molecular laye of the cerebellum and the ReHo values of the right entorhinal cortex were decreased in the IA group. taVNS increased the horizontal and vertical scores of OFT and reduced the immobility time of FST. After taVNS intervention, the ALFF and ReHo values of the right brainstem decreased. The ALFF values of the left molecular layer of the cerebellum and the ReHo values of the right entorhinal cortex were increased. The horizontal score of OFT was negatively correlated with the ALFF of right brainstem. The vertical score of OFT and immobility time of FST negatively correlated with ReHo values of the entorhinal cortex. Conclusion: taVNS alleviates depression state in the rodent model of FD possibly mediated by the enhancement of local neural coordination in the right entorhinal cortex and suppression of spontaneous neural activity in right brainstem. taVNS may have a therapeutic potential for depression in FD patients.