Transcutaneous auricular vagus nerve stimulation would be an alternative to implantable cervical vagus nerve stimulation in some situation

Implantable cervical vagus nerve stimulation(i VNS) is a representative and promising neuromodulation.However,the invasive nature restricts its application.Traditional auricular acupuncture treatment has a long history.The auricular branch of the vagus nerve(ABVN) is a branch on the surface of the ear.Some studies demonstrates that transcutaneous auricular vagus nerve stimulation(ta VNS) would achieve similar effects as i VNS.Ta VNS and i VNS share a common anatomical basis and acting mechanism.In this article,we made a comparison between i VNS and ta VNS in indications and efficacy.The recent studies have revealed similar clinical efficacy of ta VNS,ta VNS would expand the indication of i VNS.Highquality clinical evidences are needed before ta VNS become be an alternative of i VNS.

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application

Whether in the West or the East,the connection between the ear and the rest of the body has been explored for a long time.Especially in the past century or more,the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy,and finally the concept of transcutaneous auricular vagus nerve stimulation(taVNS)has been proposed.The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear.In the past two decades,taVNS has been a topic of basic,clinical,and transformation research.It has been applied as an alternative to drug treatment for a variety of diseases.Based on the rapid understanding of the application of taVNS to human health and disease,some limitations in the development of this field have also been gradually exposed.Here,we comprehensively review the origin and research status of the field.

Effect of transcutaneous auricular vagus nerve stimulation on fasting blood glucose and serum insulin concentration in Zucker diabetes fatty rats

Objective:To observe the influence of transcutaneous auricular vagus nerve stimulation(taVNS) on fasting plasma glucose(FPG) and serum insulin(INS) in Zucker diabetes fatty(ZDF) rats and explore the regulatory effect of taVNS on blood glucose in ZDF rats.Methods:A total of 20 male ZDF rats were randomized into a model group and a taVNS group,10 rats in each one.Besides,the other 10 Zucker Lean(ZL) rats were selected to be a control group.The rats in the control group were fed with common forage and those in the model group and the taVNS group were fed with high-sugar and high-fat forage.The intervention of electric stimulation was applied in the rats of taVNS group,with 2/15 Hz in frequency,disperse-dense wave and 2 mA in intensity.Each intervention lasted 30 min,once a day,consecutively for 12 weeks.No any intervention was given in the control group and the model group.The body mass and FPG level were recorded once every 2 weeks in the rats.After the experiment,the rats were sacrificed and blood sample was collected.Enzyme linked immunosorbent assay(ELISA) was adopted to determine the level of serum INS in the rats.Results:After the modeling,compared with the control group,the body mass and FPG level were all higher(P <0.05,P <0.01) and the concentration of serum INS was lower(P <0.01) in the rats of the model group.After intervention,compared with the model group,the body mass was lower in week 6 to 10(P <0.01,P <0.05),FPG level was lower in week 8 to 12(P <0.01,P <0.05) and serum INS concentration was higher(P <0.01) in the rats of the taVNS group.Conclusion:TaVNS apparently improves in hyperglycemia in ZDF rats and increases serum insulin concentration in the rats.

Transcutaneous auricular vagus nerve stimulation for functional dyspepsia:A randomized controlled trial

Objectives:To observe the clinical long-term therapeutic effect on functional dyspepsia(FD) in the comparative study of transcutaneous auricular vagus nerve stimulation(taVNS) with transcutaneous auricular none-vagus nerve stimulation(tnVNS).Methods:A total of 90 FD patients were randomized into a taVNS group and a tnVNS group,45 cases in each one.The patients in both the taNVS group and the tnVNS group were treated 5 times a week,30 min each time,for 4 weeks totally.Before treatment,after treatment and in follow-up visit,overall symptom points,functional dyspepsia-related quality of life questionnaire(FDQOL),Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD) and self-rating depression scale(SDS) were adopted to evaluate the severity of the symptoms and observe the clinical therapeutic effect of patients.Results:Compared with the scores before treatment,the overall symptom points,FDDQL,HAMA,HAMD and SDS at each time point after treatment were all lower in the patients of the taVNS group.The scores of FDDQL after treatment were almost all higher than that before treatment in the self-comparison of each group.All of the above differences were significant statistically(all P <0.05).Compared with the tnVNS group,the overall symptom points,FDDQL, HAMA,HAMD and SDS at each time point after treatment were all lower in the taVNS group and the score of FDDQL was higher,indicating the statistical differences(all P<0.05).Conclusion:Transcutaneous auricular vagus nerve stimulation is applicable for the treatment of functional dyspepsia.Compared with the control group,taVNS obtains a better long-term effect.

Preliminary single-arm study of brain effects during transcutaneous auricular vagus nerve stimulation treatment of recurrent depression by resting-state functional magnetic resonance imaging

OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging(f MRI).METHODS:Twenty-five patients with recurrent depression were enrolled in a single-arm trial of ta VNS treatment for eight weeks.Clinical results were assessed by 17-item Hamilton Depression Rating Scale(HAMD-17),Hamilton Anxiety Scale(HAMA),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS),and Ruminative Response Scale(RRS)scales.Resting-state f MRI was conducted to explore the brain effects before and after treatment.For the functional connectivity(FC)analysis,the bilateral nucleus accumbens,globus pallidus,caudate,and putamen were selected as seeds.Finally,the correlations between FC and the clinical scale scores were calculated.RESULTS:After treatment,the patients’scores of HAMD-17,HAMA,SDS,SAS,and RRS were significantly decreased(P<0.05).FC was considerably decreased between the following areas:the left globus pallidus and the right postcentral gyrus,inferior parietal gyrus,the right globus pallidus and the left superior marginal gyrus,postcentral gyrus,superior parietal gyrus,inferior parietal gyrus,precuneus,right postcentral gyrus,superior marginal gyrus,and inferior parietal gyrus,between the right caudate and the right lingual gyrus,calcarine gyrus,and cerebellum.Changes in FC between the right globus pallidus and the left inferior parietal gyrus,between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment(before,P=0.003,r=-0.6;after,P=0.009,r=-0.54).The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS(P=0.026,r=-0.474).The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS(P=0.016,r=-0.513).CONCLUSIONS:Recurrent depression could be effectively treated with ta VNS.The changes in brain FC involving the basal ganglia,default mode,and sensorimotor networks provide insight into the effects of ta VNS treatment on recurrent depression.

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.

The Anticonvulsant Effect of Transcutaneous Auricular Vagus Nerve Stimulation is Associated with Balancing the Autonomic Dysfunction in Rats

Objective:The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats.Methods:Healthy adult male Sprague-Dawley rats were anesthetized with an intraperitoneal injection of 10% urethane.Seizures were evoked by intraperitoneal injection of pentylenetetrazol(PTZ,60 mg/kg).Femoral vein catheterization was performed for injection of sympathetic agonist and antagonists.Bipolar globe silver electrodes were utilized for epidural EEG recording.Three needles were inserted separately in subcutaneous muscles of left anterior limb,right anterior limb,and left hind limb to record ECG signals.ta-VNS was performed at auricular concha.Results:In comparison with preictal state,the mean heart rate(HR) increased slightly during epileptic seizures(P<0.05).In comparison with ictal state,the mean HR decreased a little at postictal state(P<0.05).When continuous epileptic seizures in EEG traces occurred(in ictal state),vein injection of propranolol hydrochloride(sympathetic antagonist) suppressed the epileptic seizures.When epileptic seizures occurred rarely(in postictal state),vein injection of adrenaline hydrochloride(sympathetic agonist) exacerbated the epileptic seizures.In comparison with prestimulation,the integral of EEG traces after ta-VNS decreased(P<0.05),the mean HR decreased(P<0.05),and the high power(HF) of HRV increased(P<0.05) after ta-VNS.Conclusion:The results showed that autonomic dysfunction occurred in epileptic rats characterized by enhanced sympathetic nerve activity.Epileptic seizures in EEG traces decreased,HR decreased and HF increased after ta-VNS,which indicated that ta-VNS may suppress epileptic seizures via balancing the autonomic dysfunction.

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study

OBJECTIVE:To evaluate the clinical effect of transcutaneous auricular vagus nerve nerve stimulation(ta VNS)on disorders of consciousness(DOC)patients with Coma Recovery Scale-Revised(CRS-R)and cerebral cortex activity by electroencephalogram(EEG)detection.METHODS:Randomized controlled methods were used to evaluate the clinical effect of ta VNS on patients with DOC.Twelve patients with initial CRS-R of 6-10 were randomly divided into the treatment group of ta VNS and control group of transcutaneous non-auricular vague nerve stimulation(tn VNS).According to clinical diagnosis,the treatment group was divided into vegetative state(VS)group and minimally conscious state(MCS)group.RESULTS:The energy of delta and beta bands is positively correlated with the brain activity of patients.ta VNS has different regulatory effects on patients with different conscious States.In ta VNS group,the energy of delta band in local brain regions changed significantly.Significant changes in brain connection activity were limited to local brain regions.While in patients with MCS in the ta VNS group,delta and beta band energy significantly changed in multiple brain regions and crossbrain connection activity also changed significantly.CONCLUSION:These findings suggest that ta VNS may be a related extra method for arousing patients’awakening by improving brain connection activity.And the effect is remarkable in MCS patients.