Auricular Vagus Nerve Stimulation Research Articles

Modulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on attentional processes

BackgroundThe modulatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) on attention has varied in previous studies. This inconsistency might be attributed to the combined influence of the modulation effect...

Effect of Transcutaneous Auricular Vagus Nerve Stimulation Addition on Disability in Chronic Low Back Pain Patients: A Randomized Controlled Study

Background & objective: Low back pain is a common problem, especially in the young and middle-aged working people, and is often very resistant to the conventional management. We evaluated the impact of transcutaneous auricular vagus nerve stimulation (tVNS), applied in conjunction with an exercise treatment program, on disability in chronic low back pain patients.
 Methodology: The study was conducted from June to October 2022. Twenty-two patients aged 42.18 ± 9.91 y, with Numerical Pain Rating Scale (NPRS) score 5.64 ± 1.09 and Roland Morris Disability Questionnaire (RMDQ) score 10 ± 4.670, were randomly assigned to two groups. The control group received only exercise therapy (EXC group, n = 11), and the intervention group received exercise and tVNS therapy (EXC + tVNS group, n = 11). The primary outcome was RMDQ, measured before and after the intervention.
 Result: The mean RMDQ was significantly improved in both groups. In the intervention group the improvement was from 9.45 ± 4.44 to 2.18 ± 2.71 (P = 0.000), in the control group it was from 10.55 ± 5.05 to 2.36 ± 2.06 (P = 0.001). Inter-group comparison showed no significant difference. The effect size of the control group (2.12) was similar with the intervention group (1.98).
 Conclusion: Addition of 2-weeks tVNS to exercise therapy did not show superior effect on disability improvement compared to exercise only in chronic low back pain. Exercise alone was sufficient to improve the mean RMDQ.
 Abbreviations: CLBP: Chronic low back pain; EXC: Exercise; tVNS: Transcutaneous auricular vagus nerve stimulation; NPRS: Numerical pain rating scale; RMDQ: Roland Morris disability questionnaire
 Key words: Chronic low back pain; Disability; Exercise; Transcutaneous Auricular Vagus Nerve Stimulation
 Citation: Uzlifatin Y, Arfianti L, Wardhani IL, Hidayati HB, Melaniani S. Effect of transcutaneous auricular vagus nerve stimulation in addition to exercise on disability in chronic low back pain patients: a randomized controlled study. Anaesth. pain intensive care 2022;27(1):73−81; DOI: 10.35975/apic.v27i1.2084
 Received: December 07, 2022; Reviewed: December 28, 2022; Accepted: January 11, 2022

Higher pupillary dilation during phasic transcutaneous vagus nerve stimulation (taVNS) and its relevance to the noradrenergic system of the locus coeruleus (LC‐NE)

AbstractBackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) may affect the locus coeruleus‐norepinephrine system (LC‐NE system) via modulation of the vagus nerve. The LC is our main source of NE in the brainstem and declines with age and is a potential epicentre of tau pathology in Alzheimer´s diseases (AD). Besides the excessive NE release leading to the formation of amyloid plaques, the severity and duration of AD are also related to LC cell death, decreased cortical NE levels, and accelerated tau spread. An increase in NE release in the LC accompanied by reduced inflammatory markers was achieved in animal models using phasic invasive (i)VNS. In humans, phasic taVNS leads to an increase in pupil dilation, which can serve as a proxy for LC activation. Therefore, taVNS may have the potential to increase NE release and thereby impact LC function and related links to tau pathology.MethodTwenty‐four subjects (50% women; 22.96 +/‐ 2.24 years) received time‐synchronous phasic taVNS during a fixation task (∼ 18min) while recording pupillary dilation changes, which allowed systematic testing of phasic taVNS (3 sec) with low (3 mA) and high (5 mA) intensities and low (10 Hz) and high (25 Hz) frequencies at constant pulse width (250 µs).ResultDuring on stimulation pupil dilation was higher during real (0.18±0.03) as compared to sham (0.09±0.03) stimulation (χ2 = 10.29, p = 0.001) (see Fig. 1). Likewise higher (0.21±0.03) compared to lower (0.06±0.03) intensity (χ2 = 23.02, p < 0.001) led to higher pupil dilation, while there was no significant difference between higher (0.13±0.03) and lower (0.14±0.03) frequencies (χ2 = 0.11, p = 0.74).ConclusionSystematic testing of different frequencies and intensities, while keeping the pulse width constant, showed that phasic real taVNS and higher intensity lead to higher pupillary dilation, which is consistent with animal and human studies. Furthermore, the results suggest that the influence of intensity on pupil dilation might be stronger than that of frequency. The increased pupillary dilation during phasic taVNS could be an indication of LC involvement, however, more detailed studies e.g., functional magnetic resonance imaging (fMRI) during taVNS are needed to confirm this association.

An international survey of experiences and attitudes towards transcutaneous auricular vagus nerve stimulation for people with Myalgic Encephalomyelitis/chronic fatigue syndrome

ABSTRACT Background and objectives: Myalgic encephalomyelitis (ME) is a complex, multi-system neurological condition. Dysfunction of the autonomic nervous system is a primary feature in diagnostic criteria, and management may include attempts to stimulate the parasympathetic nervous system. Transcutaneous auricular vagus nerve stimulation is an intervention that has been researched in neurological disorders, e.g. epilepsy, depression. While little evidence exists for its use in ME, this survey aims to explore the experiences and attitudes of people with ME to this intervention. Methods A 31-question online survey was devised and released on ME websites, Twitter and Facebook pages. People with ME read the information sheet and followed an online link to the survey. The survey was open for four weeks and all answers were anonymous. Results 116 responses were received. 56% of respondents reported favourable effects. Benefits of transcutaneous auricular vagus nerve stimulation were identified in relation to post exertional malaise, pain, gut problems, urinary problems, mental health, and the ability to leave the house. 67.2% of respondents would recommend the intervention to other people with ME. However, 4.3% would not recommend it and 6% reported it made them worse. 8.6% received support in setting up the device from healthcare workers. Conclusion The survey highlights that many people with ME experience significant benefits from using transcutaneous auricular vagus nerve stimulation; however due to potential negative effects there is the need for formal intervention studies to clearly identify safe parameters.

Transcutaneous auricular vagus nerve stimulation on upper limb motor function with stroke: a functional near-infrared spectroscopy pilot study

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) emerges as a promising neuromodulatory technique. However, taVNS uses left ear stimulation in stroke survivors with either left or right hemiparesis. Understanding its influence on the cortical responses is pivotal for optimizing post-stroke rehabilitation protocols.ObjectiveThe primary objective of this study was to elucidate the influence of taVNS on cortical responses in stroke patients presenting with either left or right hemiparesis and to discern its potential ramifications for upper limb rehabilitative processes.MethodsWe employed functional near-infrared spectroscopy (fNIRS) to ascertain patterns of cerebral activation in stroke patients as they engaged in a “block transfer” task. Additionally, the Lateralization Index (LI) was utilized to quantify the lateralization dynamics of cerebral functions.ResultsIn patients exhibiting left-side hemiplegia, there was a notable increase in activation within the pre-motor and supplementary motor cortex (PMC-SMC) of the unaffected hemisphere as well as in the left Broca area. Conversely, those with right-side hemiplegia displayed heightened activation in the affected primary somatosensory cortex (PSC) region following treatment.Significantly, taVNS markedly amplified cerebral activation, with a pronounced impact on the left motor cortical network across both cohorts. Intriguingly, the LI showcased consistency, suggesting a harmonized enhancement across both compromised and uncompromised cerebral regions.ConclusionTaVNS can significantly bolster the activation within compromised cerebral territories, particularly within the left motor cortical domain, without destabilizing cerebral lateralization. TaVNS could play a pivotal role in enhancing upper limb functional restoration post-stroke through precise neuromodulatory and neuroplastic interventions.

The effect of transcutaneous auricular vagus nerve stimulation on cycling ergometry and recovery in healthy young individuals.

It is aimed to examine the potential benefits and effects of the use of transcutaneous auricular vagus nerve stimulation (VNS) for sporting purposes on recovery, fatigue, and sportive performance level. In this study, 90 people between the ages of 18-23 were participated. They were randomly divided into three groups as bilateral sham, unilateral left, and bilateral VNS. A 4-day protocol was applied to the participants. Cycling exercise was performed with maximum performance for 30min under the same watt load. Pulse, systolic and diastolic blood pressure, distance, pain, fatigue, lactic acid level, and autonomic nervous system were evaluated. Within the groups, there was a statistically significant difference between the data (p<.05) except for the distance covered parameter. When we compare the groups, in addition to the distance traveled in all groups, there is no statistically significant difference in the 1st day 1st measurement and 2nd measurement data of all parameters (p>.05 When we compared the data according to days, there was a statistically significant difference between bilateral stimulation (BS) and unilateral stimulation, only pain and fatigue levels (p<.05). In our study, we saw that BS application gave positive results in reducing pain and fatigue due to cycling exercise compared to other applications. Similar results were obtained when we evaluated the data on a daily basis. We believe that VNS will be beneficial in reducing pain and fatigue, especially during and after the competition halftime.

Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials.

In 2021, the U.S. Food and Drug Administration (FDA) approved paired vagus nerve stimulation (VNS) for patients with moderate-to-severe upper extremity motor impairments following chronic ischemic stroke. Previous meta-analyses have shown that VNS may impact stroke rehabilitation, but each has some limitations. PubMed, Ovid, Cochrane Library, ScienceDirect, Web of Science and WHO ICTRP databases were searched until July 14, 2022 for randomized controlled trials (RCTs). We defined primary outcomes as Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT). Subgroup analyses included types of VNS, time since onset and long-term effects. Secondary outcomes included adverse events of VNS. Eight RCTs involving 266 patients were analyzed, of which five used direct VNS and three transcutaneous auricular VNS. The results revealed that VNS enhanced upper extremity function via FMA-UE (SMD = 0.73; 95% CI: 0.48 to 0.99; P < 0.00001) and WMFT (SMD = 0.82; 95% CI:0.52 to 1.13; P < 0.00001) in comparison to the control group, but showed no significant change on long-term effects of FMA-UE (SMD = 0.69; 95% CI: - 0.06 to 1.44; P = 0.07). There was no difference in adverse events between the VNS and control groups (RR = 1.16; 95% CI: 0.46 to 2.92; P = 0.74). For stroke victims with upper limb disabilities, VNS paired with rehabilitation was significantly safe and effective. More high-quality multicentric RCTs are needed to validate this conclusion.

Use of non-invasive transcutaneous auricular vagus nerve stimulation: neurodevelopmental and sensory follow-up.

To assess the impact of non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) paired with oral feeding on long-term neurodevelopmental and sensory outcomes. We tested 21 of 35 children who as infants were gastrostomy tube (G-tube) candidates and participated in the novel, open-label trial of taVNS paired with oral feeding. To evaluate possible effects on development at 18-months after infant taVNS, we performed the Bayley-III (n = 10) and Sensory Profile (SP-2, n = 12) assessments before the COVID pandemic, and Cognitive Adaptive Test (CAT), Clinical Linguistics and Auditory Milestone (CLAMS), Ages and Stages Questionnaire (ASQ), and Peabody Developmental Motor Scales-2 gross motor tests as possible during and after the pandemic. We compared outcomes for infants who attained full oral feeds during taVNS ('responders') or received G-tubes ('non-responders'). At a mean of 19-months, taVNS 'responders' showed significantly better general sensory processing on the SP-2 than 'non-responders'. There were no differences in other test scores, which were similar to published outcomes for infants who required G-tubes. This is the first report of neurodevelopmental follow-up in infants who received taVNS-paired feeding. They had similar developmental outcomes as historical control infants failing oral feeds who received G-tubes. Our data suggests that infants who attained full oral feeds had better sensory processing.

Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial

BackgroundVagus nerve stimulation is an investigational anti-inflammatory therapy targeting the nervous system to modulate immune activity. This study evaluated the efficacy and safety of transcutaneous auricular VNS (ta-VNS) in patients with pediatric-onset Crohn’s disease (CD) or ulcerative colitis (UC).MethodsParticipants were 10–21 years of age with mild/moderate CD or UC and fecal calprotectin (FC) > 200 ug/g within 4 weeks of study entry. Subjects were randomized to receive either ta-VNS targeting the cymba conchae of the external left ear, or sham stimulation, of 5 min duration once daily for a 2-week period, followed by a cross over to the alternative stimulation for an additional 2 weeks. At week 4, all subjects received ta-VNS of 5 min duration twice daily until week 16. Primary study endpoints were clinical remission, and a ≥ 50% reduction in FC level from baseline to week 16. Heart rate variability measurements and patient-reported outcome questionnaires were completed during interval and week 16 assessments.ResultsTwenty-two subjects were enrolled and analyzed (10 CD, 12 UC). Six of 10 with CD had a wPCDAI > 12.5 and 6/12 with UC had a PUCAI > 10 at baseline, correlating to mild to moderate symptom activity. Among the 12 subjects with active symptomatic disease indices at baseline, clinical remission was achieved in 3/6 (50%) with CD and 2/6 (33%) with UC at week 16. Despite all subjects having FC levels ≥ 200 within 4 weeks of enrollment, five subjects (4 UC, 1 CD) had FC levels < 200 at the baseline visit and were excluded from the FC analysis. Of the remaining 17, median baseline FC was 907 µg/g (IQR 411–2,120). At week 16, 11/17 (64.7%) of those with baseline FC ≥ 200 had a ≥ 50% reduction in FC (95% CI 38.3—85.8). In the UC subjects, there was an 81% median reduction in FC vs baseline (833 µg/g; p = 0.03) while in the CD subjects, median reduction in FC at 16 weeks was 51% (357 µg/g; p = 0.09). There were no safety concerns.ConclusionNoninvasive ta-VNS attenuated signs and symptoms in a pediatric cohort with mild to moderate inflammatory bowel disease.Trial RegistrationNCT03863704—Date of registration 3/4/2019.

Transcutaneous auricular vagus nerve stimulation in the treatment of disorders of consciousness: mechanisms and applications.

This review provides an in-depth exploration of the mechanisms and applications of transcutaneous auricular vagus nerve stimulation (taVNS) in treating disorders of consciousness (DOC). Beginning with an exploration of the vagus nerve's role in modulating brain function and consciousness, we then delve into the neuroprotective potential of taVNS demonstrated in animal models. The subsequent sections assess the therapeutic impact of taVNS on human DOC, discussing the safety, tolerability, and various factors influencing the treatment response. Finally, the review identifies the current challenges in taVNS research and outlines future directions, emphasizing the need for large-scale trials, optimization of treatment parameters, and comprehensive investigation of taVNS's long-term effects and underlying mechanisms. This comprehensive overview positions taVNS as a promising and safe modality for DOC treatment, with a focus on understanding its intricate neurophysiological influence and optimizing its application in clinical settings.

Meniere Disease treated with transcutaneous auricular vagus nerve stimulation combined with betahistine Mesylate: A randomized controlled trial

BackgroundMeniere Disease is a clinical condition defined by hearing loss, tinnitus, and aural fullness symptoms, there are currently no any medications approved for its treatment. ObjectiveTo determine whether taVNS as an adjunctive therapy could relieve symptoms and improve the quality of life in patients with Meniere disease. MethodsIn this Single-center, single blind, randomized trial, participants were assigned to transcutaneous auricular vagus nerve stimulation (taVNS) group and sham taVNS group. The primary outcome measures comprised Tinnitus Handicap Inventory, Dizziness Handicap Inventory, Pure Tone Auditory, Visual analogue scale of aural fullness. Secondary outcome measures comprised the 36-Item Short Form Health Survey, video head impulse test, and the caloric test. ResultsAfter 12 weeks, the THI (−11.00, 95%CI, −14.87 to −7.13; P < 0.001), DHI (−47.26, 95%CI, −50.23 to −44.29; P < 0.001), VAS of aural fullness (−2.22, 95%CI, −2.95 to −1.49; P<0.01), and Pure Tone Thresholds (−7.07, 95%CI, −9.07 to −5.06; P<0.001) were significantly differed between the two groups. In addition, SF36(14.72, 95%CI, 11.06 to 18.39; P < 0.001), vHIT (RD, 0.26, 95 % CI, −0.44 to −0.08, RR, 0.43, 95 % CI, 0.22 to 0.83, P < 0.01), and the caloric test (RD, −0.24, 95 % CI, −0.43 to −0.04, RR, 0.66, 95 % CI, 0.44 to 0.95, P = 0.02) have significant difference between two group, respectively. ConclusionsThese findings suggest that taVNS combined with Betahistine Mesylate relieve symptoms and improve the quality of life for patients with Meniere Disease. taVNS can be considered an adjunctive therapy in treatment of Meniere Disease. Trial registrationClinicalTrials.gov Identifier: NCT05328895.

Causal influence of brainstem response to transcutaneous vagus nerve stimulation on cardiovagal outflow

BackgroundThe autonomic response to transcutaneous auricular vagus nerve stimulation (taVNS) has been linked to the engagement of brainstem circuitry modulating autonomic outflow. However, the physiological mechanisms supporting such efferent vagal responses are not well understood, particularly in humans. HypothesisWe present a paradigm for estimating directional brain-heart interactions in response to taVNS. We propose that our approach is able to identify causal links between the activity of brainstem nuclei involved in autonomic control and cardiovagal outflow. MethodsWe adopt an approach based on a recent reformulation of Granger causality that includes permutation-based, nonparametric statistics. The method is applied to ultrahigh field (7T) functional magnetic resonance imaging (fMRI) data collected on healthy subjects during taVNS. ResultsOur framework identified taVNS-evoked functional brainstem responses with superior sensitivity compared to prior conventional approaches, confirming causal links between taVNS stimulation and fMRI response in the nucleus tractus solitarii (NTS). Furthermore, our causal approach elucidated potential mechanisms by which information is relayed between brainstem nuclei and cardiovagal, i.e., high-frequency heart rate variability, in response to taVNS. Our findings revealed that key brainstem nuclei, known from animal models to be involved in cardiovascular control, exert a causal influence on taVNS-induced cardiovagal outflow in humans. ConclusionOur causal approach allowed us to noninvasively evaluate directional interactions between fMRI BOLD signals from brainstem nuclei and cardiovagal outflow.

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy.

Transcutaneous auricular vagus nerve stimulation (taVNS) has potential clinical application for autism spectrum disorder (ASD). At-home sessions are necessary to allow delivery of repeated sessions, and remove burden on patients for daily visits, and reduce costs of clinic delivery. Our objective was to validate a protocol for remote supervised administration for home delivery of taVNS using specially designed equipment and platform. An open-label design was followed involving administration by caretakers to 12 patients with ASD (ages:7-16). Daily 1-h sessions over 2 weeks were administered under remote supervision. The primary outcome was feasibility, which was assessed by completion rate, stimulation tolerability, and confirmation of programmed stimulation delivery. The secondary measures were initial efficacy assessed by Childhood Anxiety Sensitivity Index-Revised (CASI-R), Parent Rated Anxiety Scale for Youth with ASD (PRAS-ASD), and Clinician Global Impression (CGI) scales. Sleep measures were also tracked using Cleveland Adolescent Sleep Questionnaire (CASQ). Across 132 sessions, we obtained an 88.5% completion rate. A total of 22 expected adverse events were reported with headache being the most common followed by transient pain, itchiness, and stinging at the electrode site. One subject dropped out of the study unrelated to the stimulation or the study. Average scores of anxiety (CASI-R, PRAS-ASD, and CGI) and sleepiness (CASQ) were all improved at the 2 week time point. While not powered to determine efficacy, benefits were suggested in this open label pilot. Remotely supervised, proxy-administered, at-home delivery of taVNS is feasible in patients with ASD. Initial efficacy supports pursuing larger scale trials.

Effect of transcutaneous auricular vagus nerve stimulation on the splenic α7nAchR/JAK2/STAT3 signaling pathway in LPS-induced depressive-like behavior rats

To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the improvement of depressive-like behavior and the splenic α7 nicotinic acetylcholine receptor (α7nAchR) / Janus kinase 2 (JAK2 / signal transducer and activator of transcription 3 (STAT3) signaling pathway in lipopolysaccharide (LPS)-induced depressive-like behavior rats, so as to investigate the antidepressant mechanism of taVNS. SD rats were randomly divided into SD control group, SD model group and SD taVNS group, and α7nAchR knockout rats were also randomly divided into α7 control group, α7 model group and α7 taVNS group, with 6 rats in each group. Rat model of depressive-like behavior was established by intraperitoneal injection of LPS (1 mg/kg). Rats in both SD taVNS and α7 taVNS groups received taVNS intervention once a day (2 Hz/15 Hz, 2 mA, 30 min) from 7 days before LPS injection to 2 days after LPS injection, respectively. The mean speed, activity time and side immobility time in the open field test were recorded after taVNS. The contents of interleukin 10 (IL-10) and chemokine (C-X-C motif) ligand 1 (CXCL1) in serum were detected by electrochemiluminescence multifactorial method. The splenic phosphorylated (p)-JAK2 and p-STAT3 protein expressions were detected by Western blot. Compared with their respective control groups, the mean speed and active time were reduced (P<0.01, P<0.05, P<0.001) and the side immobility time was increased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels were up-regulated (P<0.01, P<0.05, P<0.001), and splenic p-JAK2 protein expressions were down-regulated (P<0.05, P<0.01) in SD and α7nAchR knockout rats, and splenic p-STAT3 protein expression were down-regulated (P<0.05) in SD rats after LPS injection. Following taVNS intervention and in comparison with the model group , the mean speed and active time were increased (P<0.01) and the side immobility time was decreased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels down-regulated (P<0.05), while splenic p-JAK2 and p-STAT3 protein expressions were up-regulated (P<0.01, P<0.001) in the SD taVNS group rather than in the α7 taVNS group. Compared with SD taVNS group, the α7 taVNS group showed increased (P<0.001, P<0.05) side immobility time in the open field test and serum IL-10, decreased splenic p-JAK2 and p-STAT3 protein expressions (P<0.01, P<0.05). taVNS may exert anti-inflammatory effects through modulating the splenic α7nAchR/JAK2/STAT3 signaling pathway, thereby ameliorating LPS-induced depressive-like behavior in rats.

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation.

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.

Transcutaneous auricular Vagus Nerve Stimulation and Median Nerve Stimulation reduce acute stress in young healthy adults: a single-blind sham-controlled crossover study.

Stress is a major determinant of health and wellbeing. Conventional stress management approaches do not account for the daily-living acute changes in stress that affect quality of life. The combination of physiological monitoring and non-invasive Peripheral Nerve Stimulation (PNS) represents a promising technological approach to quantify stress-induced physiological manifestations and reduce stress during everyday life. This study aimed to evaluate the effectiveness of three well-established transcutaneous PNS modalities in reducing physiological manifestations of stress compared to a sham: auricular and cervical Vagus Nerve Stimulation (taVNS and tcVNS), and Median Nerve Stimulation (tMNS). Using a single-blind sham-controlled crossover study with four visits, we compared the stress mitigation effectiveness of taVNS, tcVNS, and tMNS, quantified through physiological markers derived from five physiological signals peripherally measured on 19 young healthy volunteers. Participants underwent three acute mental and physiological stressors while receiving stimulation. Blinding effectiveness was assessed via subjective survey. taVNS and tMNS relative to sham resulted in significant changes that suggest a reduction in sympathetic outflow following the acute stressors: Left Ventricular Ejection Time Index (LVETI) shortening (tMNS: p = 0.007, taVNS: p = 0.015) and Pre-Ejection Period (PEP)-to-LVET ratio (PEP/LVET) increase (tMNS: p = 0.044, taVNS: p = 0.029). tMNS relative to sham also reduced Pulse Pressure (PP; p = 0.032) and tonic EDA activity (tonicMean; p = 0.025). The nonsignificant blinding survey results suggest these effects were not influenced by placebo. taVNS and tMNS effectively reduced stress-induced sympathetic arousal in wearable-compatible physiological signals, motivating their future use in novel personalized stress therapies to improve quality of life.

Pupillary response to percutaneous auricular vagus nerve stimulation in alcohol withdrawal syndrome: A pilot trial

BackgroundAutonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge. MethodsThirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA). ResultsA repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F(2,116) = 27.97, p < .001, ηp2 > .14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27). ConclusionOur study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind.

Efficacy of transcutaneous auricular vagus nerve stimulation on radiotherapy-related neuropathic pain in patients with head and neck cancers (RELAX): protocol for a multicentre, randomised, double-blind, sham-controlled trial

IntroductionRadiotherapy-related neuropathic pain (RRNP) is one of the most distressing complications after radiotherapy for head and neck cancers. Drug therapy is not sufficiently effective and has limitations in terms of...

Transcutaneous Auricular Vagus Nerve Stimulation Modulates Performance but Not Pupil Size During Nonnative Speech Category Learning.

Subthreshold transcutaneous auricular vagus nerve stimulation (taVNS) synchronized with behavioral training can selectively enhance nonnative speech category learning in adults. Prior work has demonstrated that behavioral performance increases when taVNS is paired with easier-to-learn Mandarin tone categories in native English listeners, relative to when taVNS is paired with harder-to-learn Mandarin tone categories or without taVNS. Mechanistically, this temporally precise plasticity has been attributed to noradrenergic modulation. However, prior work did not specifically utilize methodologies that indexed noradrenergic modulation and, therefore, was unable to explicitly test this hypothesis. Our goal for this study was to use pupillometry to gain mechanistic insights into taVNS behavioral effects. Thirty-eight participants learned to categorize Mandarin tones while pupillometry was recorded. In a double-blinded design, participants were divided into two taVNS groups that, as in the prior study, differed according to whether taVNS was paired with easier-to-learn tones or harder-to-learn tones. Learning performance and pupillary responses were measured using linear mixed-effects models. We found that taVNS did not have any tone-specific or group behavioral or pupillary effects. However, in an exploratory analysis, we observed that taVNS did lead to faster rates of learning on trials paired with stimulation, particularly for those who were stimulated at lower amplitudes. Our results suggest that pupillary responses may not be a reliable marker of locus coeruleus-norepinephrine system activity in humans. However, future research should systematically examine the effects of stimulation amplitude on both behavior and pupillary responses. https://doi.org/10.23641/asha.24036666.