Objective: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treatment-resistant depression (TRD). In the current study, we observed the immediate modulating brain effect of taVNS in patients with TRD using rest-state functional magnetic resonance imaging (rs-fMRI).Method: Forty patients with TRD and forty healthy controls (HCs) were recruited. Rs-fMRI was performed before and after 30 min of taVNS at baseline. The brain regions that presented significantly different the Regional Homogeneity (ReHo) between the TRD patients and HCs were selected as the ROI to calculate the functional connectivity (FC) of full brain. The correlations were estimated between the clinical scales' score and the functional brain changes.Results: Following taVNS stimulation treatment, TRD patients showed significantly reduced ReHo in the medial orbital frontal cortex (mOFC) (F = 18.06, P < 0.0001), ANCOVA of the mOFC-Based FC images revealed a significant interaction effect on the left inferior parietal gyrus (IPG) and left superior marginal gyrus (SMG) (F = 11.6615, P<0.001,F = 16.7520, P<0.0001). Among these regions, the HAMD and HAMA scores and ReHo/FC changes were not correlated.Conclusion: This study applied rs-fMRI technology to examine the effect of taVNS stimulation treatment on the brain activity of TRD. These results suggest that the brain response of TRD patients to taVNS treatment may be associated with the functional modulation of cortical regions including the medial orbital frontal cortex, the left inferior parietal gyrus, and the left superior marginal regions. Changes in these neuroimaging indices may represent the neural mechanisms underlying taVNS Immediate Stimulation treatment in TRD.

Background: Functional magnetic resonance imaging (fMRI) studies examining differences in the activity of brain networks between the first depressive episode (FDE) and recurrent depressive episode (RDE) are limited. The current study observed and compared the altered functional connectivity (FC) characteristics in the default mode network (DMN), cognitive control network (CCN), and affective network (AN) between the RDE and FDE. In addition, we further investigated the correlation between abnormal FC and clinical symptoms.Methods: We recruited 32 patients with the RDE, 31 patients with the FDE, and 30 healthy controls (HCs). All subjects underwent resting-state fMRI. The seed-based FC method was used to analyze the abnormal brain networks in the DMN, CCN, and AN among the three groups and further explore the correlation between abnormal FC and clinical symptoms.Results: One-way analysis of variance showed significant differences the FC in the DMN, CCN, and AN among the three groups in the frontal, parietal, temporal, and precuneus lobes and cerebellum. Compared with the RDE group, the FDE group generally showed reduced FC in the DMN, CCN, and AN. Compared with the HC group, the FDE group showed reduced FC in the DMN, CCN, and AN, while the RDE group showed reduced FC only in the DMN and AN. Moreover, the FC in the left posterior cingulate cortices and the right inferior temporal gyrus in the RDE group were positively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17), and the FC in the left dorsolateral prefrontal cortices and the right precuneus in the FDE group were negatively correlated with the HAMD-17.Conclusions: The RDE and FDE groups showed multiple abnormal brain networks. However, the alterations of abnormal FC were more extensive and intensive in the FDE group.

Objective: In this study, we used amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) to observe differences in local brain functional activity and its characteristics in patients with treatment-resistant depression (TRD) and non-treatment-resistant depression (nTRD), and to explore the correlation between areas of abnormal brain functional activity and clinical symptoms.Method: Thirty-seven patients with TRD, 36 patients with nTRD, and 35 healthy controls (HCs) were included in resting-state fMRI scans. ALFF and ReHo were used for image analysis and further correlation between abnormal brain regions and clinical symptoms were analyzed.Results: ANOVA revealed that the significantly different brain regions of ALFF and ReHo among the three groups were mainly concentrated in the frontal and temporal lobes. Compared with the nTRD group, the TRD group had decreased ALFF in the left/right inferior frontal triangular gyrus, left middle temporal gyrus, left cuneus and bilateral posterior lobes of the cerebellum, and increased ALFF in the left middle frontal gyrus and right superior temporal gyrus, and the TRD group had decreased ReHo in the left/right inferior frontal triangular gyrus, left middle temporal gyrus, and increased ReHo in the right superior frontal gyrus. Compared with the HC group, the TRD group had decreased ALFF/ReHo in both the right inferior frontal triangular gyrus and the left middle temporal gyrus. Pearson correlation analysis showed that both ALFF and ReHo values in these abnormal brain regions were positively correlated with HAMD-17 scores (P < 0.05).Conclusion: Although the clinical symptoms were similar in the TRD and nTRD groups, abnormal neurological functional activity were present in some of the same brain regions. Compared with the nTRD group, ALFF and ReHo showed a wider range of brain area alterations and more complex neuropathological mechanisms in the TRD group, especially in the inferior frontal triangular gyrus of the frontal lobe and the middle temporal gyrus of the temporal lobe.

Background: Studies on differences in brain function activity between the first depressive episode (FDE) and recurrent depressive episodes (RDE) are scarce. In this study, we used regional homogeneity (ReHo) and amplitude of low-frequency fluctuations (ALFF) as indices of abnormal brain function activity. We aimed to determine the differences in these indices between patients with FDE and those with RDE, and to investigate the correlation between areas of abnormal brain function and clinical symptoms.Methods: A total of 29 patients with RDE, 28 patients with FDE, and 29 healthy controls (HCs) who underwent resting-state functional magnetic resonance imaging were included in this study. The ReHo and ALFF measurements were used for image analysis and further analysis of the correlation between different brain regions and clinical symptoms.Results: Analysis of variance showed significant differences among the three groups in ReHo and ALFF in the frontal, parietal, temporal, and occipital lobes. ReHo was higher in the right inferior frontal triangular gyrus and lower in the left inferior temporal gyrus in the RDE group than in the FDE group. Meanwhile, ALFF was higher in the right inferior frontal triangular gyrus, left anterior cingulate gyrus, orbital part of the left middle frontal gyrus, orbital part of the left superior frontal gyrus, and right angular gyrus, but was lower in the right lingual gyrus in the RDE group than in the FDE group. ReHo and ALFF were lower in the left angular gyrus in the RDE and FDE groups than in the HC group. Pearson correlation analysis showed a positive correlation between the ReHo and ALFF values in these abnormal areas in the frontal lobe and the severity of depressive symptoms (P < 0.05). Abnormal areas in the temporal and occipital lobes were negatively correlated with the severity of depressive symptoms (P < 0.05).Conclusion: The RDE and FDE groups had abnormal neural function activity in some of the same brain regions. ReHo and ALFF were more widely distributed in different brain regions and had more complex neuropathological mechanisms in the RDE group than in the FDE group, especially in the right inferior frontal triangular gyrus of the frontal lobe.

Background: Neurobiological mechanisms underlying the recurrence of major depressive disorder (MDD) at different ages are unclear, and this study used the regional homogeneity (ReHo) index to compare whether there are differences between early onset recurrent depression (EORD) and late onset recurrent depression (LORD).Methods: Eighteen EORD patients, 18 LORD patients, 18 young healthy controls (HCs), and 18 older HCs were included in the rs-fMRI scans. ReHo observational metrics were used for image analysis and further correlation of differential brain regions with clinical symptoms was analyzed.Results: ANOVA analysis revealed significant differences between the four groups in ReHo values in the prefrontal, parietal, temporal lobes, and insula. Compared with EORD, the LORD had higher ReHo in the right fusiform gyrus/right middle temporal gyrus, left middle temporal gyrus/left angular gyrus, and right middle temporal gyrus/right angular gyrus, and lower ReHo in the right inferior frontal gyrus/right insula and left superior temporal gyrus/left insula. Compared with young HCs, the EORD had higher ReHo in the right inferior frontal gyrus/right insula, left superior temporal gyrus/left insula, and left rolandic operculum gyrus/left superior temporal gyrus, and lower ReHo in the left inferior parietal lobule, right inferior parietal lobule, and left middle temporal gyrus/left angular gyrus. Compared with old HCs, the LORD had higher ReHo in the right fusiform gyrus/right middle temporal gyrus, right middle temporal gyrus/right angular gyrus, and left rolandic operculum gyrus/left superior temporal gyrus, and lower ReHo in the right inferior frontal gyrus/right insula. ReHo in the right inferior frontal gyrus/right insula of patients with LORD was negatively correlated with the severity of 17-item Hamilton Rating Scale for Depression (HAMD-17) scores (r = −0.5778, p = 0.0120).Conclusion: Adult EORD and LORD patients of different ages have abnormal neuronal functional activity in some brain regions, with differences closely related to the default mode network (DMN) and the salience network (SN), and patients of each age group exhibit ReHo abnormalities relative to matched HCs.Clinical Trial Registration: [http://www.chictr.org.cn/], [ChiCTR1800014277].

In this study, we observed the sex differences in functional brain activity in patients with recurrent depressive disorder (RDE) and assessed the correlation between abnormal functional brain activity changes and clinical symptoms. A total of 40 patients with RDE (19 male and 21 female) and 42 healthy controls (HCs) (20 male and 22 female) met the inclusion criteria. Analysis of images using regional homogeneity (ReHo) and further analysis of the correlation between abnormal brain areas and clinical symptoms of the different sexes with RDE groups were carried out. For the main effects of sex (male vs. female), there were statistically significant differences in ReHo among the four groups in the right middle temporal gyrus, right thalamus, and left posterior cerebellar lobe. For the effects of the sex-by-group interaction, there were statistically significant differences in ReHo among the four groups in the left middle frontal gyrus, left precentral gyrus, and right insula. Post hoc analyses showed that compared with the female RDE group, the male RDE group had decreased ReHo in the left middle frontal gyrus and right insula. In the female RDE group, the ReHo values of the left middle frontal gyrus were positively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17) scores. This study provides new insights into the clinical targeting of different sexes for RDE.