Transcutaneous auricular vagus nerve stimulation (taVNS) decreases heart rate acutely in neonatal rats.
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ABSTRACT:
SUBMITTER: Gail MW
PROVIDER: S-EPMC10795507 | biostudies-literature | 2023 Sep-Oct
REPOSITORIES: biostudies-literature
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Transcutaneous auricular vagus nerve stimulation (taVNS) decreases heart rate acutely in neonatal rats.
Gail Melanie W MW Sims-Robinson Catrina C Boger Heather H Ergul Adviye A Mukherjee Rupak R Jenkins Dorothea D DD George Mark S MS
Brain stimulation 20230822 5
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Project description:BackgroundOptimal parameters of transcutaneous auricular vagus nerve stimulation (taVNS) are still undetermined. Given the vagus nerve's role in regulating heart rate (HR), it is important to determine safety and HR effects of various taVNS parameters.ObjectiveWe conducted two sequential trials to systematically test the effects of various taVNS parameters on HR.Methods15 healthy individuals participated in the initial two-visit, crossover exploratory trial, receiving either tragus (active) or earlobe (control) stimulation each visit. Nine stimulation blocks of varying parameters (pulse width: 100 μs, 200 μs, 500 μs; frequency: 1 Hz, 10 Hz, 25 Hz) were administered each visit. HR was recorded and analyzed for stimulation-induced changes. Using similar methods and the two best parameters from trial 1 (500μs 10 Hz and 500μs 25 Hz), 20 healthy individuals then participated in a follow-up confirmatory study.ResultsTrial 1- There was no overall effect of the nine conditions on HR during stimulation. However multivariate analysis revealed two parameters that significantly decreased HR during active stimulation compared to control (500μs 10 Hz and 500μs 25 Hz; p < 0.01). Additionally, active taVNS significantly attenuated overall sympathetic HR rebound (post-stimulation) compared to control (p < 0.001). Trial 2-For these two conditions, active taVNS significantly decreased HR compared to control (p = 0.02), with the strongest effects at 500μs 10 Hz (p = 0.032).ConclusionThese studies suggest that 60s blocks of tragus stimulation are safe, and some specific parameters modulate HR. Of the nine parameters studied, 500μs 10 Hz induced the greatest HR effects.
| S-EPMC6536129 | biostudies-literature
Project description:AimsTranscutaneous auricular vagus nerve stimulation (taVNS) is widely used to treat a variety of disorders because it is noninvasive, safe, and well tolerated by awake patients. However, long-term and repetitive taVNS is difficult to achieve in awake mice. Therefore, developing a new taVNS method that fully mimics the method used in clinical settings and is well-tolerated by awake mice is greatly important for generalizing research findings related to the effects of taVNS. The study aimed to develop a new taVNS device for use in awake mice and to test its reliability and effectiveness.MethodsWe demonstrated the reliability of this taVNS device through retrograde neurotropic pseudorabies virus (PRV) tracing and evaluated its effectiveness through morphological analysis. After 3 weeks of taVNS application, the open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behaviors, and the Y-maze test and novel object recognition test (NORT) were used to evaluate recognition memory behaviors, respectively.ResultsWe found that repetitive taVNS was well tolerated by awake mice, had no effect on anxiety-like behaviors, and significantly improved memory.ConclusionOur findings suggest that this new taVNS device for repetitive stimulation of awake mice is safe, tolerable, and effective.
| S-EPMC11388527 | biostudies-literature
Project description:Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.
| S-EPMC6867597 | biostudies-literature
Project description:Brain electrical stimulation techniques take advantage of the intrinsic plasticity of the nervous system, opening a wide range of therapeutic applications. Vagus nerve stimulation (VNS) is an approved adjuvant for drug-resistant epilepsy and depression. Its non-invasive form, auricular transcutaneous VNS (atVNS), is under investigation for applications, including cognitive improvement. We aimed to study the effects of atVNS on brain connectivity, under conditions that improved memory persistence in CD-1 male mice. Acute atVNS in the cymba conchae of the left ear was performed using a standard stimulation protocol under light isoflurane anesthesia, immediately or 3 h after the training/familiarization phase of the novel object-recognition memory test (NORT). Another cohort of mice was used for bilateral c-Fos analysis after atVNS administration. Spearman correlation of c-Fos density between each pair of the thirty brain regions analyzed allowed obtaining the network of significant functional connections in stimulated and non-stimulated control brains. NORT performance was enhanced when atVNS was delivered just after, but not 3 h after, the familiarization phase of the task. No alterations in c-Fos density were associated with electrostimulation, but a significant effect of atVNS was observed on c-Fos-based functional connectivity. atVNS induced a clear reorganization of the network, increasing the inter-hemisphere connections and the connectivity of locus coeruleus. Our results provide new insights into the effects of atVNS on memory performance and brain connectivity extending our knowledge of the biological mechanisms of bioelectronics in medicine.
| S-EPMC9081882 | biostudies-literature
Project description:Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.
| S-EPMC9772204 | biostudies-literature
Project description:BackgroundChildren with frequently relapsing nephrotic syndrome (FRNS) and steroid resistant nephrotic syndrome (SRNS) are exposed to immunosuppressant medications with adverse side effects and variable efficacy. Transcutaneous auricular vagus nerve stimulation (taVNS) modulates the immune system via the inflammatory reflex and has become a therapy of interest for treating immune-mediated illnesses.MethodsAn open-label, pilot study of tavNS for five minutes daily for 26 weeks via a TENS 7000 unit was conducted.ResultsThree FRNS participants and 4 SRNS participants had a mean age of 9.5±4.2 years (range 4 to 17). Those with FRNS remained relapse-free during the study period; two participants continued treatment and remained in remission for 15 and 21 months, respectively. Three SRNS participants experienced a reduction in first morning UPC (mean of 42%, range 25-76%). Although UPC decreased (13.7%) in one SRNS participant with congenital nephrotic syndrome, UPC remained in nephrotic range. All but one participant (non-compliant with treatment) experienced a reduction in TNF (7.33pg/mL vs. 5.46pg/mL, p=0.03). No adverse events or side effects were reported.ConclusionstaVNS was associated with clinical remission in FRNS and moderately reduced proteinuria in non-congenital SRNS. Further study of taVNS as a treatment for nephrotic syndrome in children is warranted. ClinicalTrials.gov Identifier: NCT04169776, Registered November 20, 2019, https://clinicaltrials.gov/ct2/show/NCT04169776 .
| S-EPMC8790887 | biostudies-literature
Project description:IntroductionTranscutaneous auricular vagus nerve stimulation (taVNS) is a promising technique for modulating vagal afferent fibers non-invasively and has shown therapeutic potential in neurological, cognitive, and affective disorders. While previous research highlights its efficacy, the safety profile of taVNS has been less extensively examined.MethodsThis study therefore aimed to systematically investigate side effects of taVNS in a large pooled dataset consisting of n = 488 participants, utilizing a standardized questionnaire to assess ten reported side effects. Analyses included effects of stimulation type (interval vs. continuous), stimulation duration, stimulation intensity and participant characteristics (age and gender) as potential modulators.ResultsThe findings support the safety of taVNS, with minimal and mild side effects reported across participants (M = 1.86, SD = 1.36). Although participants receiving sham stimulation were 32.4% less likely to report unpleasant feelings compared to participants receiving taVNS, this effect was driven primarily by low-end ratings (specifically, a rating of 1, indicating not at all when experiencing the corresponding side effect), thus suggesting limited clinical relevance. Interval stimulation notably reduced the likelihood of some side effects, particularly for neck pain, dizziness and unpleasant feelings, suggesting potential for optimizing taVNS protocols. Stimulation intensity and duration showed few statistically significant, but clinically minimal (i.e., very small) effects.ConclusionOverall, these findings demonstrate a favorable safety profile of taVNS, with mostly mild and transient effects, supporting its use as a suitable non-invasive tool in both research and clinical applications.
| S-EPMC11841445 | biostudies-literature
Project description:BackgroundElectrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters.ObjectiveWe developed a taVNS/fMRI system to enable concurrent electrical stimulation and fMRI acquisition to compare the effects of taVNS in relation to control stimulation.MethodsWe enrolled 17 healthy adults in this single-blind, crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in healthy volunteers, participants received either left tragus (active) or earlobe (control) stimulation at 500 μs 25 HZ for 60 s (repeated 3 times over 6 min). Whole brain fMRI analysis was performed exploring the effect of: active stimulation, control stimulation, and the comparison. Region of interest analysis of the midbrain and brainstem was also conducted.ResultsActive stimulation produced significant increased BOLD signal in the contralateral postcentral gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum. Control stimulation produced BOLD signal activation in the contralateral postcentral gyrus. In the active vs. control contrast, tragus stimulation produced significantly greater BOLD increases in the right caudate, bilateral anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate.ConclusionStimulation of the tragus activates the cerebral afferents of the vagal pathway and combined with our review of the literature suggest that taVNS is a promising form of VNS. Future taVNS/fMRI studies should systematically explore various parameters and alternative stimulation targets aimed to optimize this novel form of neuromodulation.
| S-EPMC6487660 | biostudies-literature
Project description:Transcutaneous auricular vagus nerve stimulation (taVNS) bears therapeutic potential for a wide range of medical conditions. However, previous studies have found substantial interindividual variability in responsiveness to taVNS, and no reliable predictive biomarker for stimulation success has been developed so far. In this study, we investigate pupil size and event-related pupil response as candidate biomarkers. Both measures have a direct physiological link to the activity of the locus coeruleus (LC), a brainstem structure and the main source of norepinephrine in the brain. LC activation is considered one of the key mechanisms of action of taVNS, therefore, we expected a clear increase of the pupillary measures under taVNS compared to sham (placebo) stimulation, such that it could serve as a prospective predictor for individual clinical and physiological taVNS effects in future studies. We studied resting pupil size and pupillary responses to target stimuli in an auditory oddball task in 33 healthy young volunteers. We observed stronger pupil responses to target than to standard stimuli. However, and contrary to our hypothesis, neither pupil size nor the event-related pupil response nor behavioral performance were modulated by taVNS. We discuss potential explanations for this negative finding and its implications for future clinical investigation and development of taVNS.
| S-EPMC6685960 | biostudies-literature
Project description:Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.
| S-EPMC11278058 | biostudies-literature