Auricular Vagus Nerve Stimulation Ameliorates Functional Dyspepsia with Depressive-Like Behavior and Inhibits the Hypothalamus-Pituitary-Adrenal Axis in a Rat Model.

BACKGROUND: The hypothalamus-pituitary-adrenal axis is the most important endocrine system to control irritability response. Functional dyspepsia (FD) is closely related to irritability. This study aimed to preliminarily explore the corticotropin-releasing factor (CRF) mechanism of auricular vagus nerve stimulation (aVNS) for FD model rats. METHODS: Sprague-Dawley adult male rats were randomly divided into normal group, model group, aVNS group, and sham-aVNS group. Except for the normal rats, all other rats were induced into the FD model through tail-clamping stimulation for 3 weeks. Once the rat model was developed successfully, rats in the aVNS group and sham-aVNS group were intervened with aVNS or sham-aVNS for 2 weeks. No intervention was given to rats in the normal and model groups. The effect of aVNS was assessed. The expressions of hippocampal corticotropin-releasing hormone receptor 1 (CRHR1), hypothalamus CRF, adrenocorticotropic hormone (ACTH), and corticosterone in serum were assessed. RESULTS: 1. Compared with normal rats, model-developing rats showed FD-like behavior. 2. Compared with model rats, rats in the aVNS group showed an improved general condition score and gastric motility, and increased horizontal and vertical motion scores. 3. The release of corticosterone, ACTH in serum, and CRF in the hypothalamus all increased in model rats but decreased with aVNS instead of sham-aVNS. 4. The expression of hippocampus CRHR1 was lower in model rats but higher in the aVNS group. CONCLUSION: aVNS ameliorates gastric motility and improves the mental state in the FD-like rat, probably via inhibiting the CRF pathway.

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature.

OBJECTIVES: After 20 years of development, there is confusion in the nomenclature of transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN). We performed a systematic review of transcutaneous stimulation of ABVN in nomenclature. MATERIALS AND METHODS: A systematic search of the literature was carried out, using the bibliographic search engine PubMed. The search covered articles published up until June 11, 2020. We recorded the full nomenclature and abbreviated nomenclature same or similar to transcutaneous stimulation of ABVN in the selected eligible studies, as well as the time and author information of this nomenclature. RESULTS: From 261 studies, 67 full nomenclatures and 27 abbreviated nomenclatures were finally screened out, transcutaneous vagus nerve stimulation and tVNS are the most common nomenclature, accounting for 38.38% and 42.06%, respectively. In a total of 97 combinations of full nomenclatures and abbreviations, the most commonly used nomenclature for the combination of transcutaneous vagus nerve stimulation and tVNS, accounting for 30.28%. Interestingly, the combination of full nomenclatures and abbreviations is not always a one-to-one relationship, there are ten abbreviated nomenclatures corresponding to transcutaneous vagus nerve stimulation, and five full nomenclatures corresponding to tVNS. In addition, based on the analysis of the usage habits of nomenclature in 21 teams, it is found that only three teams have fixed habits, while other different teams or the same team do not always use the same nomenclature in their paper. CONCLUSIONS: The phenomenon of confusion in the nomenclature of transcutaneous stimulation of ABVN is obvious and shows a trend of diversity. The nomenclature of transcutaneous stimulation of ABVN needs to become more standardized in the future.

Increased grey matter volume and associated resting-state functional connectivity in chronic spontaneous urticaria: A structural and functional MRI study.

BACKGROUND AND PURPOSE: Chronic itch is one of the most common irritating sensations, yet its mechanisms have not been fully elucidated. Although some studies have revealed relationships between itching and brain function, the structural changes in the brain induced by chronic itching, such as those accompanying chronic spontaneous urticaria (CSU), remain unclear. In this study, we aimed to explore the potential changes in brain structure and the associated functional circuitry in CSU patients to generate insights to aid chronic itch management. METHODS: Forty CSU patients and forty healthy controls (HCs) were recruited. Seven-day urticaria activity score (UAS7) values were collected to evaluate clinical symptoms. Voxel-based morphometry (VBM) and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess structural changes in the brain and associated changes in functional circuitry. RESULTS: Compared with HCs, CSU patients had significantly increased grey matter (GM) volume in the right premotor cortex, left fusiform cortex, and cerebellum. UAS7 values were positively associated with GM volume in the left fusiform cortex. In CSU patients relative to HCs, the left fusiform cortex as extracted by VBM analysis demonstrated decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex (mPFC), premotor cortex, primary motor cortex (MI), and cerebellum and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex (SI), and secondary somatosensory cortex (SII). The left cerebellum as extracted from VBM analysis demonstrated decreased functional connectivity with the right supplementary motor area (SMA) and MI in CSU patients relative to HCs. CONCLUSIONS: Our findings indicate that patients suffering from chronic itching conditions, such as CSU, are likely to demonstrate altered GM volume in some brain regions. These changes may affect not only the sensorimotor area but also brain regions associated with cognitive function.

Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder is an early sign of neurodegenerative disease. This study aimed to quantitatively evaluate iron content in idiopathic rapid eye movement sleep behavior disorder patients using quantitative susceptibility mapping and to examine the potential of this technique to identify the prodromal stage of α-synucleinopathies. METHODS: Twenty-five idiopathic rapid eye movement sleep behavior disorder patients, 32 Parkinson's disease patients, and 50 healthy controls underwent quantitative susceptibility mapping. The mean magnetic susceptibility values within the bilateral substantia nigra, globus pallidus, red nucleus, head of the caudate nucleus, and putamen were calculated and compared among groups. The relationships between the values and the clinical features of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease were measured using correlation analysis. RESULTS: Idiopathic rapid eye movement sleep behavior disorder patients had elevated iron in the bilateral substantia nigra compared with healthy controls. Parkinson's disease patients had increased iron in the bilateral substantia nigra, globus pallidus, and left red nucleus compared with healthy controls and had elevated iron levels in the bilateral substantia nigra compared with idiopathic rapid eye movement sleep behavior disorder patients. Mean magnetic susceptibility values were positively correlated with disease duration in the left substantia nigra in idiopathic rapid eye movement sleep behavior disorder patients. CONCLUSIONS: Quantitative susceptibility mapping can detect increased iron in the substantia nigra in idiopathic rapid eye movement sleep behavior disorder, which becomes more significant as the disorder progresses. This technique has the potential to be an early objective neuroimaging marker for detecting α-synucleinopathies. © 2019 International Parkinson and Movement Disorder Society.

The Dysfunction of the Cerebellum and Its Cerebellum-Reward-Sensorimotor Loops in Chronic Spontaneous Urticaria.

Chronic spontaneous urticaria (CSU) is a common itchy skin disease. Despite its prevalence, the neuropathology of CSU is uncertain. In this study, we explored resting state functional connectivity (rs-FC) changes in CSU, as well as how the symptom changes following intervention can modulate rs-FC. Forty patients and 40 healthy controls (HCs) were recruited. Following an intervention, 32 patients participated in a second scan approximately 6 weeks after the first scan. Compared with healthy controls, CSU subjects exhibited higher regional homogeneity (ReHo) values in the cerebellum, which were positively associated with urticaria activity scores over 7 days (UAS7) at baseline. After an intervention accompanied with clinical improvement, we found that ReHo values decreased at the cerebellum and increased at the bilateral primary somatosensory cortex (SI)/primary motor cortex (MI)/supplementary motor area (SMA). Using the cerebellum as a seed, CSU subjects exhibited increased rs-FC with reward regions when compared with HCs and exhibited decreased rs-FC at the right orbitofrontal cortex and right sensorimotor region following the intervention. The improvement rate values were positively associated with reduced rs-FC values in the two regions. Using the cluster of SI/MI/SMA as a seed, CSU patients exhibited decreased rs-FC with the left putamen, caudate, accumbens, and thalamus following the intervention. These results demonstrate the altered cerebellar activity and cerebellum-reward-sensorimotor loops in CSU.

[Effect of Needle Embedded in Neiguan (PC6) on Changes of ECG in Chronic Myocardial Ischemia Model Mini-pigs].

Objective To observe the effect of needle embedded in Neiguan (PC6) on electro- cardiogram (ECG) changes in model mini-pigs with chronic myocardial ischemia. Methods The protein shrink narrow ring (Ameroid Ring) was placed in the proximal part of the left coronary anterior descend- ing branch of 12 Chinese mini-pigs to prepare animal model. One died during the modeling. Chronic myo- cardial ischemia mini-pig models were established after 4 weeks. Successfully modeled 11 mini-pigs were divided into the test group (n =6) and the control group (n =5). Needle were embedded in Neiguan (PC6) of the test group and Zusanli (ST36) of the control group at week 4 after modeling. Electroacupuncture (EA) at corresponding acupoint twice (once before embedding and at week 2 after embedding) , 20 min each time. Changes of Q wave of ECG, heart rate, and ST-T interval were observed in the two groups be- fore and after modeling, before and after EA. Results Compared with before modeling in the same group, the absolute value of Q wave both increased in the two groups after modeling (P <0. 05, P <0. 01J. No statistical difference existed in heart rate in the two groups between before and after modeling (P> 0. 05). Compared with before needling in the same group, ST-T interval was prolonged in the test group (P <0. 05). Compared with the control group at the same time point, the absolute value of Q wave was re- duced before EA, ST-T interval was prolonged after EA in the test group (P <0. 05). No statistical differ- ence existed in heart rate between the control group and the test group before EA (P >0. 05). Conclusion Needle embedded in Neiguan (PC6) could arrive at therapeutic effect of myocardial ischemia possibly through improving myocardial blood supply.

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.

Transcutaneous Auricular Vagus Nerve Stimulation Modulating the Brain Topological Architecture of Functional Network in Major Depressive Disorder: An fMRI Study.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective in regulating mood and high-level cognition in patients with major depressive disorder (MDD). This study aimed to investigate the efficacy of taVNS treatment in patients with MDD and an altered brain topological organization of functional networks. METHODS: Nineteen patients with MDD were enrolled in this study. Patients with MDD underwent 4 weeks of taVNS treatments; resting-state functional magnetic resonance imaging (rs-fMRI) data of the patients were collected before and after taVNS treatment. The graph theory method and network-based statistics (NBS) analysis were used to detect abnormal topological organizations of functional networks in patients with MDD before and after taVNS treatment. A correlation analysis was performed to characterize the relationship between altered network properties and neuropsychological scores. RESULTS: After 4 weeks of taVNS treatment, patients with MDD had increased global efficiency and decreased characteristic path length (Lp). Additionally, patients with MDD exhibited increased nodal efficiency (NE) and degree centrality (DC) in the left angular gyrus. NBS results showed that patients with MDD exhibited reduced connectivity between default mode network (DMN)-frontoparietal network (FPN), DMN-cingulo-opercular network (CON), and FPN-CON. Furthermore, changes in Lp and DC were correlated with changes in Hamilton depression scores. CONCLUSIONS: These findings demonstrated that taVNS may be an effective method for reducing the severity of depressive symptoms in patients with MDD, mainly through modulating the brain's topological organization. Our study may offer insights into the underlying neural mechanism of taVNS treatment in patients with MDD.

Altered resting-state and dynamic functional connectivity of hypothalamic in first-episode depression: A functional magnetic resonance imaging study.

The hypothalamus is an important component of the hypothalamic-pituitary-adrenal axis and an important brain region of the limbic system. Twenty-four first depressive episode(FDE) patients and 25 healthy controls were recruited for this study. The hypothalamus was used as a seed to observe the characteristics of resting state and dynamic functional connectivity (FC) changes in FDE patients, and further observed the correlation between the different brain regions and clinical symptoms. The results found that compared with the HC group, the FDE group showed sFC was increased of the left hypothalamus with right superior parietal gyrus and right middle temporal gyrus, and dFC was increased of the left hypothalamus with left inferior occipital gyrus. And sFC was increased of the right hypothalamus with right orbital part of inferior frontal gyrus, right supplementary motor area, and right middle temporal gyrus, and the dFC was also increased of right hypothalamus with right superior parietal gyrus and left middle temporal gyrus. In addition,there was a negative correlation between dFC values of the right hypothalamus with the right superior parietal gyrus and clinical symptoms in the FDE group. This study provides new insights into understanding the altered neuropathological mechanisms of the hypothalamic circuit in FDE.

The abnormalities of brain function in females with primary insomnia: a resting-state functional magnetic resonance imaging study.

Background: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC). Materials and methods: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function. Results: ALFF values were increased in the Cerebelum_4_5_L, as well as decreased ALFF in the bilateral Frontal_Sup_Medial (SFGmed), Angular_L (ANG.L), Parietal_Inf_R (IPL.R), SupraMarginal_R (SMG.R), and Postcentral_R (PoCG.R). ReHo values were increased in the Temporal_Pole_Mid_R (TPOsup.R), as well as decreased ReHo in the Insula_R (INS.R), Frontal_Inf_Oper_R (ORBinf.R), Putamen_R (PUT.R), Rolandic_Oper_R (ROL.R), bilateral Cingulum_Post (PCG), bilateral Frontal_Sup_Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular_R and Frontal_Sup_Medial_L. Conclusion: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability.

Neural signatures of default mode network subsystems in first-episode, drug-naive patients with major depressive disorder after 6-week thought induction psychotherapy treatment.

Evidence indicates that the default mode network (DMN) plays a crucial role in the neuropathology of major depressive disorder (MDD). However, the neural signatures of DMN subsystems in MDD after low resistance Thought Induction Psychotherapy (TIP) remain incompletely understood. We collected functional magnetic resonance imaging data from 20 first-episode, drug-naive MDD and 20 healthy controls (HCs). The DMN was segmented into three subsystems and seed-based functional connectivity (FC) was computed. After 6-week treatment, the significantly reduced FCs with the medial temporal lobe memory subsystem in MDD at baseline were enhanced and were comparable to that in HCs. Changed Hamilton Depression Rating Scale scores were significantly related with changed FC between the posterior cingulate cortex (PCC) and the right precuneus (PCUN). Further, changed serotonin 5-hydroxytryptamine levels were significantly correlated with changed FCs between the PCC and the left PCUN, between the posterior inferior parietal lobule and the left inferior temporal gyrus, and between the retrosplenial cortex and the right inferior frontal gyrus, opercular part. Finally, the support vector machine obtained an accuracy of 67.5% to distinguish between MDD at baseline and HCs. These findings may deepen our understanding of the neural basis of the effects of TIP on DMN subsystems in MDD.

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.

A predictive study of the efficacy of transcutaneous auricular vagus nerve stimulation in the treatment of major depressive disorder: An fMRI-based machine learning analysis.

BACKGROUND: In order to improve taVNS efficacy, the usage of fMRI to explore the predictive neuroimaging markers would be beneficial for screening the appropriate MDD population before treatment. METHODS: A total of 86 MDD patients were recruited in this study, and all subjects were conducted with the clinical scales and resting-state functional magnetic resonance imaging (fMRI) scan before and after 8 weeks' taVNS treatment. A two-stage feature selection strategy combining Machine Learning and Statistical was used to screen out the critical brain functional connections (FC) that were significantly associated with efficacy prediction, then the efficacy prediction model was constructed for taVNS treating MDD. Finally, the model was validated by separated the responding and non-responding patients. RESULTS: This study showed that taVNS produced promising clinical efficacy in the treatment of mild and moderate MDD. Eleven FCs were selected out and were found to be associated with the cortico-striatal-pallidum-thalamic loop, the hippocampus and cerebellum and the HAMD-17 scores. The prediction model was created based on these FCs for the efficacy prediction of taVNS treatment. The R-square of the conducted regression model for predicting HAMD-17 reduction rate is 0.44, and the AUC for classifying the responding and non-responding patients is 0.856. CONCLUSION: The study demonstrates the validity and feasibility of combining neuroimaging and machine learning techniques to predict the efficacy of taVNS on MDD, and provides an effective solution for personalized and precise treatment for MDD.

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.

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.

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.

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.

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.

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.

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-).