Auricular Vagus Research Articles

A transient decrease in heart rate with unilateral and bilateral galvanic vestibular stimulation in healthy humans.

The study of cardiovascular function with galvanic vestibular stimulation has provided evidence on the neural structures that are involved in the vestibulo-autonomic reflex. This study determined if the effect on heart rate using galvanic vestibular stimulation persists after provoking a sympathetic response and if this response differs when using unilateral or transmastoid (bilateral) stimulation. We analysed heart rate and heart rate variability using unilateral and transmastoid galvanic vestibular stimulation combined with cardiovascular reflex evoked by postural change in 24 healthy human subjects. Three electrode configurations were selected for unilateral stimulation considering the anatomical location of each semicircular canal. We compared recordings performed in seated and standing positions, and with unilateral and transmastoid stimulation. With subjects seated, a significant transient decrease in heart rate was observed with unilateral stimulation. With transmastoid stimulation, heart rate decreased in both seated and standing positions. Average intervals between normal heartbeats recorded with stimulation resemble parasympathetic cardiac function induced by auricular vagal nerve stimulation. Our results indicate that unilateral stimulation does not eliminate the natural heart rate increase caused by orthostatic hypotension. In contrast, transmastoid stimulation provoked a transient reduction in heart rate, even when subjects were standing. These responses should be considered while performing experiments with galvanic vestibular stimulation and subsequent effects in cardiac regulation mechanisms.

The effects of transcutaneous auricular vagal nerve stimulation on pupil size

ObjectiveMechanisms of action and optimal stimulation parameters of transcutaneous auricular vagus nerve stimulation (taVNS) are currently unknown. Pupil size has gained attention as a promising biomarker of vagal activation in different studies on animal models. The aim of this study is to investigate the effects of taVNS on pupil diameter in healthy subjects. MethodsAll subjects received taVNS at the left external acoustic meatus and control stimulation at the left earlobe during the same experimental session. Different intensities (0.5 mA; 1.0 mA; 2.0 mA; 3.0 mA) for both conditions were tested. Tonic pupil size was recorded in both eyes at baseline and during each stimulation using an infrared-automated pupillometer in three different illuminance conditions (scotopic, mesopic, photopic). ResultsIn scotopic illuminance condition, a significant interaction between intensity and condition (real vs control) was found for the left eye. Post-Hoc analysis showed that during real taVNS at 2 mA, pupil size was significantly larger in comparison to baseline and 2 mA control stimulation. ConclusionsOur study demonstrates that taVNS induces pupil dilation under specific illuminance conditions and at specific stimulation intensity. SignificanceThe effects of taVNS are strictly dependent on technical aspects, such as stimulation parameters and experimental set-up.

Auricular vagal nerve stimulation enhances gastrointestinal motility and improves interstitial cells of Cajal in rats treated with loperamide.

Gastrointestinal (GI) motility disorders affect a large proportion of the population with limited treatment options. The aims of this study were to investigate the potential of a non-invasive method of auricular vagal nerve stimulation (aVNS) for treating GI dysmotility and to explore possible mechanisms involving slow waves and interstitial cells of Cajal (ICC). Normal rats were treated daily with loperamide for 1 week and then treated, while still on daily loperamide, with aVNS/Sham-aVNS for another 1week. Gastric emptying (GE), small intestine transit (SIT), and GI slow waves were measured. The plasma level of pancreatic polypeptide (PP) and noradrenaline (NE) was assessed by ELISA. ICC in the gastric antrum were detected by immunohistochemistry. (a) aVNS significantly increased the percentage of normal GI slow waves (p<0.05 for both fasting and postprandial states, vs. Sham-aVNS) and accelerated GE (p<0.05, vs. Sham-aVNS) and SIT (p<0.05, vs. Sham-aVNS) impaired by loperamide. (b) aVNS increased plasma PP (p<0.01) and decreased plasma NE (p<0.01), compared with Sham-aVNS. (c) Gastric ICC was decreased by loperamide (p<0.01) but increased after aVNS (p<0.01, vs. Sham aVNS). Loperamide induces upper GI dysmotility. aVNS accelerates upper GI transit and improving pace-making activity mediated via the ICC. Non-invasive aVNS may have a therapeutic potential for upper GI dysmotility.

The effects of transcutaneous auricular vagal nerve stimulation on cognition in healthy individuals: A meta-analysis.

Transcutaneous auricular vagal nerve stimulation (taVNS) may benefit cognition in healthy adults but may differentially affect specific domains of cognitive function. Currently, optimal stimulation parameters of taVNS have yet to be identified and the overall effectiveness of this approach remains unclear. A literature review and random effects meta-analysis evaluated the effects of taVNS on cognitive performance outcomes across domains of function and outcome metrics (accuracy and response times). Subgroup meta-analyses and meta-regression models explored the moderating effects of stimulation parameters on performance outcomes. Meta-analyses on 19 eligible studies indicated a weighted effect size of 0.21 for the effect of taVNS on overall cognitive performance, with significant effects on measures of executive function and measures of accuracy. Parameter meta-analyses indicated that stimulation site was most associated with improvements in executive function (gtragus = 2.39, gcymba concha = 0.48; Q = 39.84, p < .0001; β = -2.33, p = .03). taVNS may improve cognition, particularly executive function, and stimulation parameters may differentially influence outcomes. Continued research into the effects of taVNS as well as optimal stimulation parameters will be beneficial. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Transcutaneous auricular vagal nerve stimulation inhibits hypothalamic P2Y1R expression and attenuates weight gain without decreasing food intake in Zucker diabetic fatty rats.

Zucker diabetic fatty (ZDF) rats that harbor a mutation in the leptin receptor innately develop type 2 diabetes (T2D) with obesity. Transcutaneous auricular vagal nerve stimulation (taVNS) has an antidiabetic effect in ZDF rats. However, the underlying mechanisms of the weight-gain attenuating effect in ZDF rats by taVNS is still unclear. This study aimed to assess whether the weight-gain attenuating effect of taVNS in ZDF rats is associated with changes in the central nervous system (CNS) expression of P2Y1 receptors (P2Y1R). Adult male ZDF rats were subjected to taVNS and transcutaneous non-vagal nerve stimulation (tnVNS). Their food intake and body weight were recorded daily and weekly, respectively. P2Y1R expression in the hypothalamus, amygdala, and hippocampus was evaluated by western blotting. Hypothalamic P2Y1R expressing cells were detected using immunohistochemistry. Naïve ZDF rats were much heavier (p < 0.05) than their lean littermates (ZL rats), with elevated hypothalamic P2Y1R expression (p < 0.05). Further, taVNS but not tnVNS attenuated weight gain (p < 0.05) without decreasing food intake (p > 0.05) and suppressed hypothalamic P2Y1R expression in ZDF rats (p < 0.05). Moreover, P2Y1R showed major expression in astrocytes of ZDF rats' hypothalamus. ZDF rats innately develop obesity associated with elevated hypothalamic P2Y1R expression. taVNS attenuates weight gain in ZDF rats without changes in food intake, suggesting increased energy expenditure. Whether the reduced hypothalamic P2Y1R expression in response to taVNS is mechanistically linked to the increased energy expenditure remains to be determined.

Transcutaneous auricular vagal nerve stimulation improves functional dyspepsia by enhancing vagal efferent activity.

This study was designed to investigate whether transcutaneous auricular vagal nerve stimulation (taVNS) would be able to improve major pathophysiologies of functional dyspepsia (FD) in patients with FD. Thirty-six patients with FD (21 F) were studied in two sessions (taVNS and sham-ES). Physiological measurements, including gastric slow waves, gastric accommodation, and autonomic functions, were assessed by the electrogastrogram (EGG), a nutrient drink test and the spectral analysis of heart rate variability derived from the electrocardiogram (ECG), respectively. Thirty-six patients with FD (25 F) were randomized to receive 2-wk taVNS or sham-ES. The dyspeptic symptom scales, anxiety and depression scores, and the same physiological measurements were assessed at the beginning and the end of the 2-wk treatment. In comparison with sham-ES, acute taVNS improved gastric accommodation (P = 0.008), increased the percentage of normal gastric slow waves (%NSW, fasting: P = 0.010; fed: P = 0.007) and vagal activity (fasting: P = 0.056; fed: P = 0.026). In comparison with baseline, 2-wk taVNS but not sham-ES reduced symptoms of dyspepsia (P = 0.010), decreased the scores of anxiety (P = 0.002) and depression (P < 0.001), and improved gastric accommodation (P < 0.001) and the %NSW (fasting: P < 0.05; fed: P < 0.05) by enhancing vagal efferent activity (fasting: P = 0.015; fed: P = 0.048). Compared with the HC, the patients showed increased anxiety (P < 0.001) and depression (P < 0.001), and decreased gastric accommodation (P < 0.001) and %NSW (P < 0.001) as well as decreased vagal activity (fasting: P = 0.047). The noninvasive taVNS has a therapeutic potential for treating nonsevere FD by improving gastric accommodation and gastric pace-making activity via enhancing vagal activity.NEW & NOTEWORTHY Treatment of functional dyspepsia is difficult due to various pathophysiological factors. The proposed method of transcutaneous auricular vagal nerve stimulation improves symptoms of both dyspepsia and depression/anxiety, and gastric functions (accommodation and slow waves), possibly mediated via the enhancement of vagal efferent activity. This noninvasive and easy-to-implement neuromodulation method will be well received by patients and healthcare providers.

Transcutaneous Auricular Vagal Nerve Stimulation and Disorders of Consciousness: A Hypothesis for Mechanisms of Action.

Disorders of consciousness (DoC) are the hallmark of severe acquired brain injuries characterized by abnormal activity in important brain areas and disruption within and between brain networks. As DoC's therapeutic arsenal is limited, new potential therapies such as transcutaneous auricular vagal nerve stimulation (taVNS) have recently been explored. The potential of taVNS in the process of consciousness recovery has been highlighted in recent studies with DoC patients. However, it is not clear how taVNS plays a role in the recovery of consciousness. In this article, we first describe the neural correlates of consciousness, the vagus nerve anatomy and functions, along with the results of functional magnetic resonance imaging studies using taVNS. Based on consciousness recovery and taVNS mechanisms, we propose the Vagal Cortical Pathways model. This model highlights four consecutive pathways (A. Lower brainstem activation, B. Upper brainstem activation, C. Norepinephrine pathway, and D. Serotonin pathway) likely to have an impact on patients with a brain injury and DoC. Additionally, we suggest six different mechanisms of action: (1) Activation of the ascending reticular activating system; (2) Activation of the thalamus; (3) Re-establishment of the cortico-striatal-thalamic-cortical loop; (4) Promotion of negative connectivity between external and default mode networks by the activation of the salience network; (5) Increase in activity and connectivity within the external network through the norepinephrine pathway; and (6) Increase in activity within the default mode network through the serotonin pathway. This model aims to explain the potential therapeutic effects that taVNS has on brain activity in the process of consciousness recovery.

Modulatory Effects of Respiratory-Gated Auricular Vagal Nerve Stimulation on Cardiovagal Activity in Hypertension.

The objective of this study was to determine potential effects of Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) on cardiac autonomic activity in hypertensive patients.20 hypertensive subjects (57.3±6.2 years; 11 females, 9 males) were randomized to receive either active RAVANS at 25 Hz or sham stimulation for 5 consecutive days and were assessed 5 and 10 days later. Continuous electrocardiogram, pulse rate, and blood pressure signals were collected during 10-minute baseline, 30-minute stimulation, and 10-minute recovery periods for each session. LabChart was used to acquire and process heart rate variability and blood pressure indices. Percent changes of mean values during the recovery period were calculated comparing the final stimulation session and follow-up sessions to the first stimulation session. General linear models were applied to assess the effects of RAVANS on the variables evaluated, considering baseline values and sex as covariates in the models.We found that RAVANS increased high frequency (HF-HRV) power during recovery of the final stimulation session and both follow-up sessions in comparison to sham. RAVANS also lowered heart rate and increased average RR and root mean square of successive RR interval differences (RMSSD) during recovery on the final day of stimulation. No significant effects on blood pressure values were observed during these periods.These results suggest that RAVANS effectively stimulates cardiovagal activity in hypertension, with effects lasting up to 10 days. Future research incorporating larger sample sizes is needed to replicate the effects of RAVANS.Clinical Relevance- This research has implications for potential therapeutic effects of respiratory-gated tVNS on cardiovagal modulation in hypertensive patients.

Non-invasive Recording of Parasympathetic Nervous System Activity on Auricular Vagal Nerve Branch.

The function of the autonomic nervous system (ANS) influences most of the physiological mechanisms. The popular non-invasive method to estimate the activities of the autonomic nervous system (ANS) is the heart rate variability (HRV). However, the HRV cannot provide real-time information of the ANS function. The skin sympathetic nerve activity (SKNA) is a novel method to evaluate sympathetic nerve system (SNS) activity. The SKNA technique has shown promise in clinical applications but is limited to evaluating SNS activities. To date, a direct non-invasive method for measuring the parasympathetic nerve system (PNS) function is urgently needed. According to anatomy, the auricular branch of the vagus nerve (aVN) is near the concha surface. In this study, we hypothesize that we can measure the aVN activity (aVNA) with the same technique developed for SKNA recording. Flexible auricular electrodes were developed for continuous long-term recording of aVN activity. The SKNA and aVNA were simultaneously recorded during the experiment. The cold face test and cold pressor test were performed to physiologically activate ANS. The SKNA and aVNA can be obtained simultaneously, and they are correlated with the heart rate change during the physiological challenge. The aVNA has a high potential to be developed into a novel method to measure the PNS activity.

The Effect of Transcutaneous Auricular Vagal Nerve Stimulation (taVNS) on P3 Event-Related Potentials during a Bayesian Oddball Task.

Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive brain stimulation technique associated with possible modulation of norepinephrinergic (NE) activity. NE is suspected to contribute to generation of the P3 event-related potential. Recent evidence has produced equivocal evidence whether taVNS influences the P3 in healthy individuals during oddball tasks. We examined the effect of taVNS on P3 amplitudes using a novel visual Bayesian oddball task, which presented 200 sequences of three stimuli. The three consecutive stimuli in each sequence are labelled Draw 1, Draw 2 and Draw 3. In total, 47 Subjects completed this visual Bayesian oddball task under randomised sham and active taVNS stimulation in parallel with an electroencephalographic (EEG) recording. We conducted exploratory analyses of the effect of taVNS on P3 amplitudes separately for Draws. We found typical oddball effects on P3 amplitudes at Draws 1 and 2, but not Draw 3. At Draw 2, the oddball effect was enhanced during active compared to sham taVNS stimulation. These data provide evidence that taVNS influences parietal P3 amplitudes under specific circumstances. Only P3 amplitudes at Draw 2 were affected, which may relate to closure of Bayesian inference after Draw 2. Our findings seemingly support previously reported links between taVNS and the NE system.

The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine.

Gastric motility is regulated by an electrophysiological activity called slow-wave and neuronal innervations by the vagus nerve. Transcutaneous auricular vagal nerve stimulation (taVNS) has been demonstrated to have therapeutic potential for a wide range of medical conditions, including the management of gastric dysfunctions. The main objective of this study was to gain a better understanding of how non-invasive neuromodulation influences gastric slow wave under in vivo conditions. TaVNS protocols were applied in conjunction with 192-channel gastric bioelectrical mapping in porcine subjects under general anesthesia. The spatiotemporal profiles of gastric slow wave were assessed under two different taVNS protocols at 10 and 80Hz. The taVNS protocols effectively altered the interval and amplitude of gastric slow waves, but not the velocity or the percentage of spatial dysrhythmias. In the subjects that responded to the protocols, the 10Hz protocol was shown to normalize slow-wave propagation pattern in 90% of the subjects, whereas the 80Hz protocol was shown to inhibit slow waves in 60% of the subjects. Chronic responses of gastric motility and slow waves in response to taVNS should be investigated using non-invasive means in conscious subjects in future.

P65 Difference between transcutaneous auricular and cervical vagus nerve stimulation on heart rate variability

P65 Difference between transcutaneous auricular and cervical vagus nerve stimulation on heart rate variability

P83 The Effect of transcutaneous auricular Vagal Nerve Stimulation (taVNS) on Event-Related Potentials during the Fish-Lake Task

P83 The Effect of transcutaneous auricular Vagal Nerve Stimulation (taVNS) on Event-Related Potentials during the Fish-Lake Task

Concerning Auricular Vagal Nerve Stimulation: Occult Neural Networks

Auricular vagal nerve stimulation (AVNS) is an evolving neuromodulation technology that has a wide range of therapeutic applications across multiple disciplines of medical science. To date, AVNS results had been interpreted in the context of a monolog concept of the auricular branch of the vagus nerve (ABVN): that this is the sole network of the mechanism of action and/or structure in the auricular area of the stimulation in the context of activations in the brainstem nuclei, including the nucleus tractus solitarius (NTS), locus coeruleus (LC), trigeminal brainstem nuclei, and the nucleus cuneatus. This review considers the overlooked aspects of neural networks, connections, hijacking axons from cranial nerves and cervical sympathetic ganglions, the inhomogeneous distribution of perivascular sympathetic nerves, and intrinsic/extrinsic auricular muscles in the auricular zone that can explain the vagal and non-vagal nucleus activations in AVNS. In addition, the unique cortical representation of the human ear and interspecies differences in the auricula are discussed. The detailed auricular anatomy of the AVNS zone explored in the present study references structural and functional neural network information to overcome default designs and misinterpretations of existing research on AVNS to provide a better foundation for future investigations that use this modality.

Transcutaneous Auricular Vagal Nerve Stimulation for Post-coma Patients With Disorders of Consciousness

Transcutaneous Auricular Vagal Nerve Stimulation for Post-coma Patients With Disorders of Consciousness

115 – Transcutaneous Auricular Vagal Nerve Stimulation Improves Functional Dyspepsia by Enhancing Vagal Efferent Activity

115 – Transcutaneous Auricular Vagal Nerve Stimulation Improves Functional Dyspepsia by Enhancing Vagal Efferent Activity

The influence of respiration on brainstem and cardiovagal response to auricular vagus nerve stimulation: A multimodal ultrahigh-field (7T) fMRI study

BackgroundBrainstem-focused mechanisms supporting transcutaneous auricular VNS (taVNS) effects are not well understood, particularly in humans. We employed ultrahigh field (7T) fMRI and evaluated the influence of respiratory phase for optimal targeting, applying our respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) technique. HypothesisWe proposed that targeting of nucleus tractus solitarii (NTS) and cardiovagal modulation in response to taVNS stimuli would be enhanced when stimulation is delivered during a more receptive state, i.e. exhalation. MethodsBrainstem fMRI response to auricular taVNS (cymba conchae) was assessed for stimulation delivered during exhalation (eRAVANS) or inhalation (iRAVANS), while exhalation-gated stimulation over the greater auricular nerve (GANctrl, i.e. earlobe) was included as control. Furthermore, we evaluated cardiovagal response to stimulation by calculating instantaneous HF-HRV from cardiac data recorded during fMRI. ResultsOur findings demonstrated that eRAVANS evoked fMRI signal increase in ipsilateral pontomedullary junction in a cluster including purported NTS. Brainstem response to GANctrl localized a partially-overlapping cluster, more ventrolateral, consistent with spinal trigeminal nucleus. A region-of-interest analysis also found eRAVANS activation in monoaminergic source nuclei including locus coeruleus (LC, noradrenergic) and both dorsal and median raphe (serotonergic) nuclei. Response to eRAVANS was significantly greater than iRAVANS for all nuclei, and greater than GANctrl in LC and raphe nuclei. Furthermore, eRAVANS, but not iRAVANS, enhanced cardiovagal modulation, confirming enhanced eRAVANS response on both central and peripheral neurophysiological levels. Conclusion7T fMRI localized brainstem response to taVNS, linked such response with autonomic outflow, and demonstrated that taVNS applied during exhalation enhanced NTS targeting.

When a White Horse is a Horse: Embracing the (Obvious?) Overlap Between Acupuncture and Neuromodulation.

When a White Horse is a Horse: Embracing the (Obvious?) Overlap Between Acupuncture and Neuromodulation.

Auricular vagal nerve stimulation in peripheral arterial disease patients.

Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128-236] meters to 345 [95 % CI 227-463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109-210] meters to 268 [95 % CI 182-366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

Transcutaneous auricular vagal nerve stimulation (taVNS) might be a mechanism behind the analgesic effects of auricular acupuncture

BackgroundRandomized clinical trials (RCT) demonstrated that auricular acupuncture (AA) is effective in treatment of acute and chronic pain, although the mechanisms behind AA are not elucidated. MethodsThe data concerning the localization of AA points, which are commonly used to treat pain, were extracted from the meta-analysis of 17 RCTs and evaluated using the anatomical map of auricular afferent nerve supply. ResultsFifteen out of 20 specific AA points, used in the treatment of pain, are situated in areas innervated mostly by the auricular branch of the vagal nerve (ABVN), whereas sham stimulation was applied at the helix of the auricle, innervated by cervical nerves. ConclusionConsidering the clinical data relating to the anatomy of neural pathways and experimental findings of the mechanisms of transcutaneous auricular vagal nerve stimulation, the analgesic effects of AA may be explained by stimulation of ABVN.