In order to investigate the therapeutic potential of acupuncture on patients with functional dyspepsia (FD), patients were randomized to receive acupuncture at classic acupoints with manipulations (treatment group) versus acupuncture at nonacupoints without manipulation (control group) once every other day, three times a week, for one month and were followed up for three months. The primary outcomes included dyspeptic symptoms, quality of life, and mental status. The secondary outcomes included the fasting serum gastrin concentration, and frequency and propagation velocity of gastric slow waves. Sixty patients with FD were included, among whom, four dropped out. After one month's treatment, patients with FD showed significant improvements in primary (in both groups) and secondary (in the eight patients of the treatment group) outcomes as compared with baseline (P=0.0078to <0.0001); treatment group has better outcomes in all primary outcome measures (P<0.0001except for SDS (P=0.0005)). Improvements on dyspeptic symptoms persist during follow-up (better in the treatment group). Acupuncture with manual manipulation had better effects on improving dyspeptic symptoms, mental status, and quality of life in patients with FD. These effects may be related to the increased frequency and propagation speed of gastric slow waves and serum gastrin secretion.

Previous studies have found that transcutaneous auricular vagus nerve stimulation (taVNS) is clinically effective in the treatment of major depressive disorder (MDD), and its efficacy mechanism is related to modulation of the default mode network (DMN) and cognitive control network (CCN). However, the mechanism of the immediate effect of taVNS for MDD remains to be elucidated. A total of 58 patients with MDD and 54 healthy controls(HCs) were included in this study. The MDD group was treated with taVNS for 30 min (20 Hz, 4-6 mA) immediately, and we observed amplitude of low-frequency fluctuations (ALFF) abnormalities in the MDD group and changes in ALFF and functional connectivity (FC) before and after immediate treatment. The ALFF brain regions altered by taVNS induction were used as regions of interest to analyze whole-brain FC changes in the MDD group. After taVNS treatment, ALFF in the right precuneus was decreased in the MDD group. The FC of the right precuneus with the left middle frontal gyrus, the left posterior cingulate gyrus and the left angular gyrus were decreased in the MDD group. Correlation analysis showed that the FC values between the right precuneus and the left posterior cingulate gyrus in the pre-treatment MDD group was negatively correlated with the 17-item Hamilton depression rating scale scores. TaVNS has an immediate modulatory effect on DMN and CCN. It would be proposed that these functional networks may be effective targets for the long-term treatment of MDD patients with taVNS.

Primary insomnia (PI) is associated with increased spontaneous neuronal activity. Transcutaneous auricular vagus nerve stimulation (taVNS) modulates brain function, and it is an effective treatment for primary insomnia. However, whether taVNS alleviates insomnia through modulating spontaneous neuronal activity is not fully clarified. This study aims to investigate the instant effect of taVNS in modulating spontaneous neuronal activity in PI patients using resting-state functional magnetic resonance imaging (rs-fMRI). Twenty-two PI subjects underwent rs-fMRI scanning prior and immediately after 30 min treatment of taVNS controlled by twenty healthy adults. Amplitude of low frequency fluctuations (ALFF) analysis was employed to assess the difference in spontaneous neuronal activity between PI patients and healthy adults, as well as between pre-treatment and post-treatment of taVNS. The taVNS-induced altered ALFF brain areas were then selected as regions of interest to perform the resting state functional connectivity (RSFC) analysis in PI patients. The right precuneus showed significantly increased ALFF in PI patients. After immediate taVNS treatment, the ALFF was significantly decreased in the right precuneus and increased in the left middle occipital gyrus. The RSFC in right precuneus with right angular, right superior frontal gyrus, and right middle frontal gyrus was significantly decreased. This study provides insights into the instant brain effects of taVNS on PI patients.

Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD. Methods: We evaluated the effects of aVNS on visceral hypersensitivity, gastric motility and open field test (OFT) activity in iodoacetamide (IA)-treated rats. The autonomic function was assessed; blood samples and tissues were collected and analyzed by an enzyme-linked immunosorbent assay and western blot. Vagotomy was performed to investigate the role of vagal efferent nerve. Results: aVNS reduced the electromyography response to gastric distension, improved gastric emptying and increased the horizontal and vertical motion scores of the OFT in IA-treated rats. The sympathovagal ratio was increased in IA-treated rats but normalized with aVNS. The serum cytokines TNF-α, IL-6, IL-1β and NF-κBp65 were increased in IA-treated rats and decreased with aVNS. The hypothalamus–pituitary–adrenal axis was hyperactive in IA-treated rats but inhibited by aVNS. The expression of duodenal desmoglein 2 and occludin were all decreased in IA-treated rats and increased with aVNS but not sham-aVNS. Vagotomy abolished the ameliorating effects of aVNS on gastric emptying, horizontal motions, serum TNF-α and duodenal NF-κBp65. Conclusion: aVNS improves gastric motility and gastric hypersensitivity probably by anti-inflammatory mechanisms via the vago-vagal pathways. A better understanding on the mechanisms of action involved with aVNS would lead to the optimization of the taVNS methodology and promote taVNS as a non-pharmacological alternative therapy for FD.

Objectives: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear.Methods: Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes.Results: The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment.Conclusions: It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

Previous neuroimaging has paid little attention to the differences in brain network integration between patients with treatment-resistant depression(TRD) and non-TRD (nTRD), and the relationship between their impaired brain network integration and clinical symptoms has not been elucidated. Eighty one major depressive disorder (MDD) patients (40 in TRD, 41 in nTRD) and 40 healthy controls (HCs) were enrolled for the functional magnetic resonance imaging (fMRI) scans. A seed-based functional connectivity (FC) method was used to investigate the brain network abnormalities of default mode network (DMN), affective network (AN), salience network (SN) and cognitive control network (CCN) for the MDD. Finally, the correlation was analyzed between the abnormal FCs and 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores. Compared with the HC group, the FCs in DMN, AN, SN, CCN were altered in both the TRD and nTRD groups. Compared with the nTRD group, FC alterations in the AN and CCN were more abnormal in the TRD group, and the FC alterations were generally decreased at the SN in the TRD group. In addition, the FC values of right dorsolateral prefrontal cortices and left caudate nucleus in the TRD group and the FC values of right subgenual anterior cingulate cortex and left middle temporal gyrus in the nTRD group were positively correlated with HAMD-17 scale scores. Abnormal FCs are present in four brain networks (DMN, AN, SN, CCN) in both the TRD and nTRD groups. Except of DMN, FCs in AN, SN and CCN maybe underlay the neurobiological mechanism in differentiating TRD from nTRD.