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.

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.

Transcutaneous electrical cranial-auricular acupoint stimulation versus escitalopram for mild-to-moderate depression: An assessor-blinded, randomized, non-inferiority trial.

AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.

Comparative Effectiveness of Transcutaneous Auricular Vagus Nerve Stimulation vs Citalopram for Major Depressive Disorder: A Randomized Trial.

OBJECTIVES: Major depressive disorder (MDD) is one of the most common mental illnesses. This study aims to investigate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) compared with the effectiveness of citalopram, a commonly used antidepressant, in patients with depression. MATERIAL AND METHODS: A total of 107 male and female patients with MDD (55 in the taVNS group and 52 in the citalopram group) were enrolled in a prospective 12-week, single-blind, comparative effectiveness trial. Participants were recruited from the outpatient departments of three hospitals in China. Participants were randomly assigned to either taVNS treatment (eight weeks, twice per day, with an additional four-week follow-up) or citalopram treatment (12 weeks, 40 mg/d). The primary outcome was the 17-item Hamilton Depression Rating Scale (HAM-D17) measured every two weeks by trained interviewers blinded to the treatment assignment. The secondary end points included the 14-item Hamilton Anxiety Scale and peripheral blood biochemical indexes. RESULTS: The HAM-D17 scores were reduced in both treatment groups; however, there was no significant group-by-time interaction (95% CI: -0.07 to 0.15, p = 0.79). Nevertheless, we found that taVNS produced a significantly higher remission rate at week four and week six than citalopram. Both treatments were associated with significant changes in the peripheral blood levels of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and noradrenaline, but there was no significant difference between the two groups. CONCLUSION: taVNS resulted in symptom improvement similar to that of citalopram; thus, taVNS should be considered as a therapeutic option in the multidisciplinary management of MDD. Nevertheless, owing to the design of this study, it cannot be ruled out that the reduction in depression severity in both treatment groups could be a placebo effect.

The Role of Acupuncture Improving Cognitive Deficits due to Alzheimer's Disease or Vascular Diseases through Regulating Neuroplasticity.

Dementia affects millions of elderly worldwide causing remarkable costs to society, but effective treatment is still lacking. Acupuncture is one of the complementary therapies that has been applied to cognitive deficits such as Alzheimer's disease (AD) and vascular cognitive impairment (VCI), while the underlying mechanisms of its therapeutic efficiency remain elusive. Neuroplasticity is defined as the ability of the nervous system to adapt to internal and external environmental changes, which may support some data to clarify mechanisms how acupuncture improves cognitive impairments. This review summarizes the up-to-date and comprehensive information on the effectiveness of acupuncture treatment on neurogenesis and gliogenesis, synaptic plasticity, related regulatory factors, and signaling pathways, as well as brain network connectivity, to lay ground for fully elucidating the potential mechanism of acupuncture on the regulation of neuroplasticity and promoting its clinical application as a complementary therapy for AD and VCI.

Efficacy and brain mechanism of transcutaneous auricular vagus nerve stimulation for adolescents with mild to moderate depression: Study protocol for a randomized controlled trial.

BACKGROUND: Depression is a common mental illness in childhood and adolescence, with an incidence of 4%-5%; it can lead to impairments in learning and social functioning. Transcutaneous auricular vagus nerve stimulation (taVNS) is a commonly used method of auricular acupuncture point stimulation, which is regarded as an effective treatment for adults with depression. The aim of this study was to investigate the efficacy and mechanism of taVNS for adolescents with mild to moderate depression. METHODS: This randomized controlled clinical trial will include 120 patients aged 12-16 years, all of whom are diagnosed with mild to moderate depression. Patients will be randomly assigned to a taVNS group and a drug control group (sertraline hydrochloride) at a ratio of 1:1. Patients will be evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, Self-Rating Depression Scale, Self-Rating Anxiety Scale, and Pittsburgh Sleep Quality Index scores at baseline, as well as at the 2nd, 4th, 6th, 8th, and 12th weeks. To investigate the underlying neural mechanisms of taVNS treatment from the perspective of the default mode network, multimodal magnetic resonance imaging (MRI; i.e., structural MRI [sMRI], resting state MRI [rsMRI], and pseudocontinuous arterial spin-labeled [pcASL] MRI) will be used to compare cerebral images among groups. MRI data will also be collected from 40 healthy volunteers to assess whether the participants exhibit normal development of structural and functional components. DISCUSSION: Depression is the most common mental disorder in adolescence. Drug treatment can improve depression symptoms; however, the side effects of drug treatments are often severe. This study proposes a simple physiotherapy that aims to treat adolescents with mild to moderate depression. The mechanism of taVNS in the treatment of depression will also be investigated. The results of this study will provide evidence to guide the application of taVNS in adolescents with depression.

EFFECT OF-GYMNEMA SYLVESTRE, CITRULLUS COLOCYNTHIS AND ARTEMISIA ABSINTHIUM ON BLOOD GLUCOSE AND LIPID PROFILE IN DIABETIC HUMAN.

The aim of this study was to manage diabetes with medicinal plants (Gymnema sylvestre, Artemisia absinthium and Citillus colocynthis) in human patients with type II diabetes. Thirty two patients of type II diabetes from both sexes of 30-60 years age were registered for this study and distributed them into four groups, each having 8 patients. Capsules of each, Gymnema sylvestre, Artemisia absinthium and Citrullus colocynthis were given to patients twice a day for 30 days in 1 g per day dosage and investigated for glucose, triglyceride (TGL) and cholesterol level. Gymnema sylvestre reduced 37% glucose, 5% TGL, 13% cholesterol and 19% low desity lipoproteins (LDL) level in diabetic individuals. Citrullus colocynth reduced glucose, cholesterol and TGL and HDL-cholesterol level by 35, 6, 6, and 5%, respectively. Artemisia absinthium reduced 3% high desity lipoproteins (HDL) and 6% LDL level. From results, it can be concluded that the powdered Gymnema sylvestre, Citrulus colocynthis, and Artemisia absinthium possess good anti-diabetic features, however these herbal products had no significant effect on lipid profiles of the diabetic human.

[Senile dementia: differentiation of syndromes according to meridians based on the theory of "cerebral collaterals injury by toxin"].

The pathogenesis and treatments based on meridian differentiation of senile dementia are discussed through analyses and researches on the theory of "cerebral collaterals injury by toxins" and "collateral diseases". The symptoms of "Cerebral collaterals injury by toxins" are preliminary characterized by toxins and blood stasis occluding brain collaterals. "Cerebral collateral injury by toxins" and "Governor Vessel occlusion by blood stasis" are taken as the major pathogeneses of senile dementia. And the treatment should be focused on clearing the collaterals. Clearance acting as reinforcing as well as to clear and modify the Governor Vessel are taken as crucial sections in the treatment of senile dementia based on meridian differentiation. It is also the application of acupuncture-moxibustion intervention in senile dementia based on the theory of "cerebral collateral injury by toxins", which expands the application of the theory concerning "collateral diseases" in disease prevention and treatment with acupuncture-moxibustion.