Regional nigral neuromelanin degeneration in asymptomatic leucine-rich repeat kinase 2 gene carrier using MRI.

Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.

Altered functional brain activity in first-episode major depressive disorder treated with electro-acupuncture: A resting-state functional magnetic resonance imaging study.

Background: Previous studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated. Methods: Twenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed. Results: The EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus. Conclusion: EA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS.

[Analysis of influence of MR signs on Harris score in ARCO stages 2-4 femoral head necrosis].

OBJECTIVE: To analysis and determine MR signs of Harris score ARCO stages 2-4 in osteonecrosis of femoral head (ONFH). METHODS: Thirty-four patients with ONFH of ARCO stages 2 to 4 who underwent routine MR, T2 mapping, 3D-SPACE sequence examination and Harris score were retrospectively collected from January 2019 to June 2020, and 3 patients were excluded, and 31 patients were finally included, including 23 males and 8 females, aged from 18 to 62 years old with an average of(40.0±10.8) years old. Among them 21 patients with bilateral femoral head necrosis, totally 52 cases, including 17 with ARCO stage 2 patients, 24 ARCO stage 3, and 11 ARCO stage 4. MR imaging signs (femoral head collapse depth, ONFH index, bone marrow edema, hyperplasia, grade and T2 value of cartilage injury, and joint effusion) were scored and measured on the picture archiving and communication system (PACS) workstation, and the cartilage quantitative parameter T2 value was calculated and measured on Siemens postprocessing workstation. Pearson correlation analysis was used to evaluate the correlation between various MR signs and Harris score, and then multiple linear regression analysis was used to examine impact of MR signs on Harris hip score. RESULTS: Femoral head collapse depth(r=-0.563, P=0.000), grade of cartilage injury(r=-0.500, P=0.000), and joint effusion (r=-0.535, P=0.000) were negatively correlated with Harris score by Pearson correlation analysis. Multiple linear regression analysis showed that joint effusion(ß=-6.198, P=0.001) and femoral head collapse depth(ß=-4.085, P=0.014) had a significant negative impact on Harris hip score. CONCLUSION: Femoral head collapse depth and joint effusion both had significant negative relationship with Harris hip score. It is recommended to routinely evaluate femoral head collapse depth and joint effusion quantitatively and gradedly, so as to efficiently and accurately assist clinical diagnosis and treatment.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for modulating the brain activity in mild to moderate major depressive disorder: An fMRI study.

Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is an innovative, non-invasive therapy for major depressive disorder (MDD). However, its effectiveness and underlying neural mechanisms remain not fully understood. This study aimed to investigate the treatment response and neurological effects of TECAS compared to escitalopram, a commonly used depression medication, using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-one patients with mild-to-moderate MDD (34 in the TECAS group and 17 in the Escitalopram group) and 51 healthy controls (HCs) participated in the study. We employed the low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) methods to explore brain abnormalities in MDD patients and HCs. Additionally, seed-based functional connectivity (FC) analysis was conducted to examine altered brain networks before and after treatment.Compared to the HCs group, the MDD group exhibited lower ReHo and ALFF values in the right medial superior frontal gyrus (mSFG_R), indicating altered neural activity in this region. Furthermore, mSFG-based FC analysis revealed abnormal FC values in the right inferior occipital gyrus (IOG_R) and middle temporal gyrus (MTG) between after and before treatment in MDD patients. Interestingly, TECAS treatment was found to normalize these abnormal FC brain regions, suggesting its potential role in restoring neural connectivity in MDD patients. Notably, both TECAS and escitalopram demonstrated equivalent antidepressant efficacy, with both treatments showing modulatory effects on connectivity within the default mode network (DMN). The observed normalization of abnormal FC regions, including mSFG_R, IOG_R, and MTG, all belong to the DMN. In conclusion, this study sheds light on the neurological effects and treatment response of TECAS in MDD, highlighting its potential as a non-invasive therapeutic option for depressed patients.

Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study.

Objective: Motor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke. Methods: In this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl-Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects. Results: Through machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups. Conclusion: Feature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

Disruption of locus coeruleus-related functional networks in Parkinson's disease.

Locus coeruleus (LC) is severely affected in Parkinson's Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PDRBD+) and without RBD (PDRBD-). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PDRBD+ patients, whereas LC-related RSNs were less damaged in PDRBD- patients than that in patients with iRBD and PDRBD+. The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PDRBD-, and cognition and severity of RBD in patients with PDRBD+. Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PDRBD+), but are less affected in brain-first PD (PDRBD-).

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is used for treating depression but the efficacy and safety have not been well assessed. This study was conducted to evaluate the efficacy and safety of taVNS in depression. METHODS: The retrieval databases included English databases of PubMed, Web of Science, Embase, the Cochrane Library and PsycINFO, and Chinese databases of CNKI, Wanfang, VIP and Sino Med, and the retrieval period was from their inception to November 10, 2022. The clinical trial registers (ClinicalTrials.gov and Chinese Clinical Trial Registry) were also searched. Standardized mean difference and the risk ratio were used as the effect indicator and the effect size was represented by the 95 % confidence interval. Revised Cochrane risk-of-bias tool for randomized trials and the Grades of Recommendation, Assessment, Development and Evaluation system were used to assess the risk of bias and quality of evidence respectively. RESULTS: Totally, 12 studies of 838 participants were included. taVNS could significantly improve depression and reduce Hamilton Depression Scale scores. Low to very low evidence showed that taVNS had higher response rates than sham-taVMS and comparable response rates compared to antidepressants (ATD) and that taVNS combined with ATD had comparable efficacy to ATD with fewer side effects. LIMITATIONS: The number of studies in subgroups was small and the evidence quality was low to very low. CONCLUSIONS: taVNS is an effective and safe method for alleviating depression scores and had a comparable response rate to ATD.

[Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI].

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION: The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study.

INTRODUCTION: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. METHODS: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. RESULTS: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. CONCLUSION: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Shared and unique effects of ApoEε4 and pathogenic gene mutation on cognition and imaging in preclinical familial Alzheimer's disease.

BACKGROUND: Neuropsychology and imaging changes have been reported in the preclinical stage of familial Alzheimer's disease (FAD). This study investigated the effects of APOEε4 and known pathogenic gene mutation on different cognitive domains and circuit imaging markers in preclinical FAD. METHODS: One hundred thirty-nine asymptomatic subjects in FAD families, including 26 APOEε4 carriers, 17 APP and 20 PS1 mutation carriers, and 76 control subjects, went through a series of neuropsychological tests and MRI scanning. Test scores and imaging measures including volumes, diffusion indices, and functional connectivity (FC) of frontostriatal and hippocampus to posterior cingulate cortex pathways were compared between groups and analyzed for correlation. RESULTS: Compared with controls, the APOEε4 group showed increased hippocampal volume and decreased FC of fronto-caudate pathway. The APP group showed increased recall scores in auditory verbal learning test, decreased fiber number, and increased radial diffusivity and FC of frontostriatal pathway. All three genetic groups showed decreased fractional anisotropy of hippocampus to posterior cingulate cortex pathway. These neuropsychological and imaging measures were able to discriminate genetic groups from controls, with areas under the curve from 0.733 to 0.837. Circuit imaging measures are differentially associated with scores in various cognitive scales in control and genetic groups. CONCLUSIONS: There are neuropsychological and imaging changes in the preclinical stage of FAD, some of which are shared by APOEε4 and known pathogenic gene mutation, while some are unique to different genetic groups. These findings are helpful for the early identification of Alzheimer's disease and for developing generalized and individualized prevention and intervention strategies.

Auricular Vagus Nerve Stimulation Improves Visceral Hypersensitivity and Gastric Motility and Depression-like Behaviors via Vago-Vagal Pathway in a Rat Model of Functional Dyspepsia.

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-1ß 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.

Transcutaneous Electrical Cranial-Auricular Acupoint Stimulation Modulating the Brain Functional Connectivity of Mild-to-Moderate Major Depressive Disorder: An fMRI Study Based on Independent Component Analysis.

Evidence has shown the roles of taVNS and TECS in improving depression but few studies have explored their synergistic effects on MDD. Therefore, the treatment responsivity and neurological effects of TECAS were investigated and compared to escitalopram, a commonly used medication for depression. Fifty patients with mild-to-moderate MDD (29 in the TECAS group and 21 in another) and 49 demographically matched healthy controls were recruited. After an eight-week treatment, the outcomes of TECAS and escitalopram were evaluated by the effective rate and reduction rate based on the Montgomery-Asberg Depression Rating Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. Altered brain networks were analyzed between pre- and post-treatment using independent component analysis. There was no significant difference in clinical scales between TECAS and escitalopram but these were significantly decreased after each treatment. Both treatments modulated connectivity of the default mode network (DMN), dorsal attention network (DAN), right frontoparietal network (RFPN), and primary visual network (PVN), and the decreased PVN-RFPN connectivity might be the common brain mechanism. However, there was increased DMN-RFPN and DMN-DAN connectivity after TECAS, while it decreased in escitalopram. In conclusion, TECAS could relieve symptoms of depression similarly to escitalopram but induces different changes in brain networks.

Immediate modulatory effects of transcutaneous auricular vagus nerve stimulation on the resting state of major depressive disorder.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Different characteristics of striatal resting-state functional conectivity in treatment-resistant and non-treatment-resistant depression.

Major depressive disorder is associated with a reward deficit manifested by abnormal striatal function. However, differences between treatment-resistant depression (TRD) and non TRD (nTRD) in striatal whole-brain functional connectivity (FC) have not been elucidated. Thirty-eight patients with TRD, 42 patients with nTRD, and 39 healthy controls (HCs) were recruited for this study. A seed-based FC approach was used to analyze abnormalities in six predefined striatal subregion circuits in the three groups of subjects, and further explore the correlation between abnormal FC and clinical symptoms. Results revealed that compared with the nTRD group, the TRD group showed increased FC of the inferior ventral striatum with the bilateral orbital area of the middle frontal gyrus, right cerebellum posterior lobe, left parahippocampal gyrus, left middle occipital gyrus and left lingual gyrus. Compared with the HC group, the TRD group showed a wider range of altered striatal function than the nTRD group. In the TRD group, the HAMD-17 scores were positively correlated with the FC between the right VRP and the left caudate. This study provides new insights into understanding the specificity of TRD striatal circuits.

Distinct patterns of functional brain network integration between treatment-resistant depression and non treatment-resistant depression: A resting-state functional magnetic resonance imaging study.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Characterization of Resting-State Striatal Differences in First-Episode Depression and Recurrent Depression.

The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.

Sex Differences of the Functional Brain Activity in Treatment-Resistant Depression: A Resting-State Functional Magnetic Resonance Study.

The presence of different clinical symptoms in patients with treatment-resistant depression (TRD) of different sexes may be related to different neuropathological mechanisms. A total of 16 male patients with TRD, 18 female patients with TRD, 18 male healthy controls (HCs) and 19 female HCs completed this study. We used the amplitude of low frequency fluctuations (ALFF) method to analyze the results. Moreover, the correlation between abnormal brain areas and clinical symptoms in different sexes of the TRD groups was also analyzed. The effects of the sex-by-group interaction difference in ALFF among the four groups was located in the left middle frontal gyrus, left precentral gyrus and left precuneus. Post hoc comparisons revealed that the male TRD group had lower ALFF in the left middle frontal gyrus and left precentral gyrus compared with the female TRD group. There was a positive correlation between the left middle frontal gyrus, the left precuneus and the 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores, and a negative correlation between the left precentral gyrus and the HAMD-17 scores in the female TRD group. This study will provide some clinical reference value for the sex differences in neuropathological mechanisms of TRD.

Prolonged Longitudinal Transcutaneous Auricular Vagus Nerve Stimulation Effect on Striatal Functional Connectivity in Patients with Major Depressive Disorder.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions' functional connectivity (FC) in MDD patients. METHODS: Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. RESULTS: The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. CONCLUSIONS: Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.

Recognizing the role of the vagus nerve in depression from microbiota-gut brain axis.

Depression is a worldwide disease causing severe disability, morbidity, and mortality. Despite abundant studies, the precise mechanisms underlying the pathophysiology of depression remain elusive. Recently, cumulate research suggests that a disturbance of microbiota-gut-brain axis may play a vital role in the etiology of depression while correcting this disturbance could alleviate depression symptoms. The vagus nerve, linking brain and gut through its afferent and efferent branches, is a critical route in the bidirectional communication of this axis. Directly or indirectly, the vagus afferent fibers can sense and relay gut microbiota signals to the brain and induce brain disorders including depression. Also, brain changes in response to stress may result in gut hyperpermeability and inflammation mediating by the vagal efferents, which may be detrimental to depression. Notably, vagus nerve stimulation owns an anti-inflammatory effect and was proved for depression treatment. Nevertheless, depression was accompanied by a low vagal tone, which may derive from response to stress and contribute to pathogenesis of depression. In this review, we aim to explore the role of the vagus nerve in depression from the perspective of the microbiota-gut-brain axis, highlighting the relationship among the vagal tone, the gut hyperpermeability, inflammation, and depression.