Project description:OBJECTIVE:Vagus nerve stimulation (VNS) is a neuromodulation method used for treatment of epilepsy and depression. Transcutaneous VNS (tVNS) has been gaining popularity as a noninvasive alternative to VNS. Previous tVNS neuroimaging studies revealed brain (de)activation patterns that involved multiple areas implicated in tinnitus generation and perception. In this study, functional magnetic resonance imaging (fMRI) was used to explore the effects of tVNS on brain activity in patients with tinnitus. METHODS:Thirty-six patients with chronic tinnitus received tVNS to the inner tragus, cymba conchae, and earlobe (sham stimulation). RESULTS:The locus coeruleus and nucleus of the solitary tract in the brainstem were activated in response to stimulation of both locations compared with the sham stimulation. The cochlear nuclei were also activated, which was not observed in healthy subjects with normal hearing. Multiple auditory and limbic structures, as well as other brain areas associated with generation and perception of tinnitus, were deactivated by tVNS, particularly the parahippocampal gyrus, which was recently speculated to cause tinnitus in hearing-impaired patients. CONCLUSIONS:tVNS via the inner tragus or cymba conchae suppressed neural activity in the auditory, limbic, and other tinnitus-related non-auditory areas through auditory and vagal ascending pathways in tinnitus patients. The results from this study are discussed in the context of several existing models of tinnitus. They indicate that the mechanism of action of tVNS might be involved in multiple brain areas responsible for the generation of tinnitus, tinnitus-related emotional annoyance, and their mutual reinforcement.
Project description:BackgroundLow back pain is the leading cause of disability worldwide. The therapeutic management of patients with chronic LBP is challenging.ObjectivesThe aim of this study is to evaluate the effects of heat and transcutaneous electrical nerve stimulation combined on pain relief in participants with chronic low back pain.MethodsFifty participants with chronic (≥3 months) low back pain were randomly assigned to two groups: HeatTens (n=25) and control group (n=25). Primary outcome was pain. Secondary outcomes were pressure pain thresholds, temporal summation, conditioned pain modulation, fear-avoidance and beliefs questionnaire, central sensitization inventory, quality of life, and medication use. The control group received no treatment and continued usual care. After four weeks of treatment, all measurements were repeated.ResultsFifty individuals participated in this study. Significant higher pressure pain threshold measures after both 30min and 4 weeks for the lower back region and the second plantar toe were found only in the experimental group.ConclusionThe combination of heat and transcutaneous electrical nerve stimulation does not reduce pain scores in patients with chronic low back pain. Pressure pain threshold values significantly improved, showing beneficial effects of the experimental treatment. ClinicalTrials.gov: NCT03643731 (https://clinicaltrials.gov/ct2/show/NCT03643731).
Project description:tVNS enhances various memory and learning mechanisms, but there is inconclusive evidence on whether probabilistic learning can be enhanced by tVNS. Here, we tested a simplified version of the probabilistic learning task with monetary rewards in a between-participants design with left and right-sided cymba conchae and tragus stimulation (compared to sham stimulation) in a sample of healthy individuals (n = 80, 64 women, on average 26.38 years old). tVNS enhances overall accuracy significantly (p = 4.09 x 10-04) and reduces response times (p = 1.1006 x 10-49) in the probabilistic learning phase. Reinforcement learning modelling of the data revealed that the tVNS group uses a riskier strategy, dedicates more time to stimulus encoding and motor processes and exhibits greater reward sensitivity relative to the sham group. The learning advantage for tVNS relative to sham persists (p = 0.005 for accuracy and p = 9.2501 × 10-27 for response times) during an immediate extinction phase with continued stimulation in which feedback and reward were omitted. Our observations are in line with the proposal that tVNS enhances reinforcement learning in healthy individuals. This suggests that tVNS may be useful in contexts where fast learning and learning persistence in the absence of a reward is an advantage, for example, in the case of learning new habits.
Project description:BACKGROUND AND OBJECTIVES:This study is a meta-analysis of randomized controlled trials comparing the efficacy of transcutaneous electrical nerve stimulation (TENS) to a control and to other nerve stimulation therapies (NSTs) for the treatment of chronic back pain. METHODS:Citations were identified in MEDLINE, the Cochrane Library, Google Scholar, and ClinicalTrials.gov through June 2014 using the following keywords: nerve stimulation therapy, transcutaneous electrical nerve stimulation, back pain, chronic pain. Control treatments included sham, placebo, or medication only. Other NSTs included electroacupuncture, percutaneous electrical nerve stimulation, and percutaneous neuromodulation therapy. RESULTS:Twelve randomized controlled trials including 700 patients were included in the analysis. The efficacy of TENS was similar to that of control treatment for providing pain relief (standardized difference in means [SDM] = -0.20; 95% confidence interval [CI], -0.58 to 0.18; P = 0.293). Other types of NSTs were more effective than TENS in providing pain relief (SDM = 0.86; 95% CI, 0.15-1.57; P = 0.017). Transcutaneous electrical nerve stimulation was more effective than control treatment in improving functional disability only in patients with follow-up of less than 6 weeks (SDM = -1.24; 95% CI, -1.83 to -0.65; P < 0.001). There was no difference in functional disability outcomes between TENS and other NSTs. CONCLUSIONS:These results suggest that TENS does not improve symptoms of lower back pain, but may offer short-term improvement of functional disability.
Project description:ObjectiveTranscutaneous auricular vagus nerve stimulation (tVNS) may be an innovative treatment for symptoms of knee osteoarthritis (OA) due to possible shared pathological mechanisms between diminished parasympathetic function, central pain mechanisms, and knee pain. Thus, we sought to test the safety and preliminary efficacy of tVNS in people with knee OA.DesignA pilot trial in which participants received a 60-min tVNS was conducted. At baseline, immediately after, and 15 min after tVNS, we assessed knee pain, pressure pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and high-frequency power of heart rate variability (HF). We examined the extent to which these outcome measures changed after tVNS using linear mixed models.Results30 participants with knee OA were included, and all completed the intervention without any major side effects. Compared to baseline, knee pain was reduced by 1.27 (95 % CI, -1.74, -0.80) immediately after and by 1.87 (-2.33, -1.40) 15 min after tVNS; CPM improved by 0.11 (0.04, 0.19) and 0.07 (-0.01, 0.15); and HF improved by 213.29 (-0.38, 426.96) and 234.17 (20.49, 447.84). PPT and TS were not changed after tVNS.ConclusionsOur preliminary data demonstrated that tVNS may be a safe pain-relieving treatment for people with knee OA. Our findings suggest that improvement of knee pain might be derived from improvement of parasympathetic function and central pain mechanisms as no local therapy was applied. A large study is needed to confirm that tVNS is a novel intervention to ameliorate knee pain in people with knee OA.Clinical trialClinicalTrials.gov (NCT05625178).
Project description:OBJECTIVES:We aimed to assess the clinical significance of the intensity of transcutaneous vagus nerve stimulation (tVNS) in chronic tinnitus. MATERIALS AND METHODS:Four sessions of tVNS were performed over a 2-week period for 24 patients with unilateral, non-pulsatile chronic tinnitus. The cavum, cymba, and tragus were sequentially stimulated to the maximal sensory thresholds. One month later, after the four sessions, the level of tinnitus distress and changes in stimulus intensity were assessed. RESULTS:The stimulus intensity did not differ according to sex or laterality. However, a moderate positive correlation between tinnitus distress and the initial stimulus intensity was observed. This correlation was not observed during the subsequent sessions. The stimulus intensity at the cavum changed significantly (p=0.018), and notable differences in tinnitus annoyance were observed between the responders and non-responders (p=0.006). CONCLUSION:The effect of stimulus intensity on the treatment outcome seems to be limited. An increasing trend in the stimulus intensity for tinnitus annoyance at the cavum was observed in the responders. Therefore, the cavum may be an optimal stimulation site for tVNS.
Project description:ImportanceEvidence from randomized clinical trials of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia disorder is lacking.ObjectiveTo evaluate the efficacy and safety of taVNS for chronic insomnia compared with the sham taVNS.Design, setting, and participantsThis randomized clinical trial was conducted from October 2021 to December 2022 at a single center in Beijing, China. Patients with chronic insomnia disorder with a Pittsburgh Sleep Quality Index (PSQI) of at least 8 were enrolled. Statistical analysis was performed from June to September 2023.InterventionsPatients were allocated to the active taVNS group or sham taVNS group with a 1:1 ratio. Both groups received the stimulation for 30 minutes each time, twice a day, 5 consecutive days a week, with an 8-week treatment and a 12-week follow-up.Main outcomes and measuresThe primary end point was the mean change from baseline through week 8 in PSQI scores. Minimal clinically important difference was 2.5 points. Secondary outcomes included mental health, sleepiness, and fatigue. Safety was also evaluated.ResultsA total of 72 participants were randomized to either active taVNS group (36 participants; mean [SD] age, 45.2 [14.5] years; 27 [75.0%] female) or the sham taVNS group (36 participants; mean [SD] age, 44.6 [13.9] years; 31 [86.1%] female); 68 participants completed the 8-week intervention. The least-square mean changes from baseline to week 8 in PSQI were -8.2 (95% CI, -9.3 to -7.0) points in the taVNS group and -3.9 (95% CI, -5.1 to -2.7) points in the sham group. Both groups experienced statistically significant improvements from before to after the intervention. However, active taVNS showed a clinically meaningful 4.2-point greater reduction (95% CI, -5.9 to -2.6 points; P < .001; Cohen d effect size, 1.2) in PSQI compared with the sham group (minimal clinically important difference = 2.5 points). Secondary outcomes, including mental health and fatigue, showed similar favorable results. The efficacy of taVNS was sustained throughout the 20-week study period.Conclusions and relevanceIn this randomized clinical trial, taVNS significantly reduced insomnia severity. Clinically meaningful enhancements in PSQI scores were observed compared with sham stimulation, with the benefits of taVNS sustained over a 20-week period. Future multicenter clinical trials with large sample sizes are needed to validate its effectiveness across diverse populations.Trial registrationChinese Clinical Trial Registry: ChiCTR2100051319.
Project description:BackgroundTranscutaneous vagus nerve stimulation (tVNS) has emerged as a novel noninvasive adjunct therapy for advanced Parkinson's disease (PD), yet no quantitative analysis had been conducted to assess its therapeutic effect.ObjectivesThis review aimed to investigate the efficacy of tVNS on motor function, other potential clinical targets and its safety in various treatment conditions.MethodsWe searched six databases for randomized controlled trials (RCTs) that involved treating PD patients with tVNS. Primary outcome was motor functions, including severity of motor signs, functional mobility and balance, and gait parameters. Secondary outcomes were cognition, emotion, sleep related impairments, patient reported non-motor outcomes, and any adverse events. All outcomes were classified and analyzed according to the treatment duration and medication condition of an included study. Risk of bias was evaluated by referencing Cochrane risk of bias tool 1.0. Data was analyzed by Revman 5.4.Results6 RCTs with 176 PD patient were included. Several motor functions and non-motor functions measured during on-medication condition (severity of motor signs -0.48 [95% CI -0.93, -0.04], gait -0.48 [95% CI -0.85, -0.1], patients reported non-motor outcomes -0.4 [95% CI -0.78, -0.03]), improved significantly. However, verbal fluency, sleep-related impairment, and fatigue were negatively impacted by tVNS during on-medication condition. No distinct adverse events were reported.ConclusiontVNS is a relatively safe adjunct treatment for PD. It has small to moderate therapeutic effects on motor functions and may negatively impact on a few other outcomes. Quality level of the evidence is low and further research is warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024503322 (PROSPERO).
Project description:BackgroundTranscutaneous vagus nerve stimulation (tVNS) is a promising therapeutic option for major depressive disorder (MDD) in adults. Alternative third-line treatments for MDD in adolescents are scarce. Here we aimed to assess the effects of acute tVNS on emotion recognition in adolescents with MDD.MethodsAdolescents (14-17 years) with MDD (n = 33) and non-depressed controls (n = 30) received tVNS or sham-stimulation in a cross-sectional, case-control, within-subject cross-randomized controlled trial, while performing different tasks assessing emotion recognition. Correct responses, response times, and errors of omission and commission on three different computerized emotion recognition tasks were assessed as main outcomes. Simultaneous recordings of electrocardiography and electro dermal activity, as well as sampling of saliva for the determination of α-amylase, were used to quantify the effects on autonomic nervous system function.ResultstVNS had no effect on the recognition of gradually or static expressed emotions but altered response inhibition on the emotional Go/NoGo-task. Specifically, tVNS increased the likelihood of omitting a response toward sad target-stimuli in adolescents with MDD, while decreasing errors (independent of the target emotion) in controls. Effects of acute tVNS on autonomic nervous system function were found in non-depressed controls only.ConclusionsAcute tVNS alters the recognition of briefly presented facial expressions of negative valence in adolescents with MDD while generally increasing emotion recognition in controls. tVNS seems to specifically alter early visual processing of stimuli of negative emotional valence in MDD. These findings suggest a potential therapeutic benefit of tVNS in adolescent MDD that requires further evaluation within clinical trials.
Project description:IntroductionChemosensory food signals are carried by the vagus nerve (VN) from the gut to the brain and these signals contribute to communicating fullness and caloric value of the consumed food in regulatory and reward-related contexts. Here, we aimed to explore whether neural responses to flavor can be modulated through noninvasive VN stimulation, which can be done transcutaneously (transcutaneous vagus nerve stimulation [tVNS]) on the outer ear via the auricular branch of VN. The ideal stimulation location on the outer ear for tVNS is not agreed on but two candidate locations are cymba conchae and tragus.MethodsIn this study, we explore the optimal stimulation location for tVNS (cymba conchae, tragus, and cymba conchae and tragus) and timing of tVNS relative to chocolate milk presentation (during, after) in a within-participants design (15 participants). We examined various measures of efficacy; event-related potential from electroencephalogram, eye-blink rate, perceptual and hedonic aspects of flavor, swallowing behavior, and consumption behavior.ResultsWe observed no effect of stimulation location on any of the dependent variables. Unexpectedly, we observed a large effect of food consumption on spontaneous eye-blink rate.ConclusionIn conclusion, overall we did not observe a clear optimal ear location for tVNS-induced modulation of neurophysiological, perceptual, and behavioral variables. Future studies may confirm whether spontaneous eye-blink rate can be a sensitive proxy for food reward-related phasic dopamine shifts.