Respiratory-gated Auricular Vagal Afferent Nerve Research Articles

The Effects of Combined Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation and Mindfulness Meditation for Chronic Low Back Pain: A Pilot Study.

Respiratory-gated Auricular Vagal Afferent Nerve stimulation (RAVANS) is a safe nonpharmacological approach to managing chronic pain. The purpose of the current study was to examine (1) the feasibility and acceptability of RAVANS, combined with mindful meditation (MM) for chronic low back pain (CLBP), (2) the potential synergy of MM+RAVANS on improving pain, and (3) possible moderators of the influence of MM+RAVANS on pain. Pilot feasibility and acceptability study. Pain management center at large academic medical center. Nineteen adults with CLBP and previous MM training. Participants attended two sessions during which they completed quantitative sensory testing (QST), rated pain severity, and completed a MM+stimulation session. Participants received RAVANS during one visit and sham stimulation during the other, randomized in order. Following intervention, participants repeated QST. MM+RAVANS was well tolerated, acceptable, and feasible to provide relief for CLBP. Both MM+stimulation sessions resulted in improved back pain severity, punctate pain ratings, and pressure pain threshold. Individuals with greater negative affect showed greater back pain improvement from MM+RAVANS while those with greater mindfulness showed greater back pain improvement from MM+sham. Results suggest that for CLBP patients with prior MM training, the analgesic effects of MM may have overshadowed effects of RAVANS given the brief single session MM+RAVANS intervention. However, those with greater negative affect may benefit from combined MM+RAVANS.

Closed-Loop Transcutaneous Auricular Vagal Nerve Stimulation: Current Situation and Future Possibilities.

Closed-loop (CL) transcutaneous auricular vagal nerve stimulation (taVNS) was officially proposed in 2020. This work firstly reviewed two existing CL-taVNS forms: motor-activated auricular vagus nerve stimulation (MAAVNS) and respiratory-gated auricular vagal afferent nerve stimulation (RAVANS), and then proposed three future CL-taVNS systems: electroencephalography (EEG)-gated CL-taVNS, electrocardiography (ECG)-gated CL-taVNS, and subcutaneous humoral signals (SHS)-gated CL-taVNS. We also highlighted the mechanisms, targets, technical issues, and patterns of CL-taVNS. By reviewing, proposing, and highlighting, this work might draw a preliminary blueprint for the development of CL-taVNS.

Respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) modulates brain response to stress in major depression

BackgroundNegative stress significantly impacts major depressive disorder (MDD), given the shared brain circuitry between the stress response and mood. Thus, interventions that target this circuitry will have an important impact on MDD. The aim of this study was to evaluate the acute effects of a novel respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) technique in the modulation of brain activity and connectivity in women with MDD in response to negative stressful stimuli. MethodsTwenty premenopausal women with recurrent MDD in an active episode were included in a cross-over experimental study that included two functional MRI visits within one week, randomized to receive exhalatory- (e-RAVANS) or inhalatory-gated (i-RAVANS) at each visit. Subjects were exposed to a visual stress challenge that preceded and followed RAVANS. A Factorial analysis was used to evaluate the effects of RAVANS on brain activity and connectivity and changes in depressive and anxiety symptomatology post-stress. ResultsCompared with i-RAVANS, e-RAVANS was significantly associated with increased activation of subgenual anterior cingulate, orbitofrontal and ventromedial prefrontal cortices and increased connectivity between hypothalamus and dorsolateral prefrontal cortex, and from nucleus tractus solitarii to locus coeruleus and ventromedial prefrontal cortex. Changes in brain activity and connectivity after e-RAVANS were significantly associated with a reduction in depressive and anxiety symptoms. ConclusionsOur study suggests exhalatory-gated RAVANS effectively modulates brain circuitries regulating response to negative stress and is associated with significant acute reduction of depressive and anxiety symptomatology in women with recurrent MDD. Findings suggest a potential non-pharmacologic intervention for acute relief of depressive symptomatology in MDD.

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.

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.

Abstract #54: Imaging Medullary Brainstem Response to Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) at Ultrahigh-Field (7T)

Abstract #54: Imaging Medullary Brainstem Response to Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) at Ultrahigh-Field (7T)

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.

Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) effects on autonomic outflow in hypertension.

Transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN) has been proposed as a non-invasive alternative to vagus nerve stimulation (VNS). However, its cardiovagal effects are inconsistent across studies, likely due to inhomogeneity in the stimulation parameters. Here, we evaluate respiratory-gated ABVN stimulation (Respiratory-gated Auricular Vagal Afferent Nerve Stimulation, RAVANS), where the stimuli are delivered in 1 s bursts during the exhalation phase of respiration, thus mimicking the breathing-induced modulation of cardiac vagal activity. In this study, we present preliminary results from an ongoing single-arm, open label trial investigating the effects of different intensities of RAVANS in hypertensive subjects. We found that a mid-intensity RAVANS stimulation (rated as a 5 on a 0-10 scale) increases the cardiovagal tone and reduces the sympathetic tone during a paced breathing task. The present results could contribute to optimize RAVANS as a non-invasive, low-cost therapeutic intervention for hypertension.

Modulation of brainstem activity and connectivity by respiratory-gated auricular vagal afferent nerve stimulation in migraine patients.

Migraine pathophysiology includes altered brainstem excitability, and recent neuromodulatory approaches aimed at controlling migraine episodes have targeted key brainstem relay and modulatory nuclei. In this study, we evaluated the impact of respiratory-gated auricular vagal afferent nerve stimulation (RAVANS), a novel neuromodulatory intervention based on an existing transcutaneous vagus nerve stimulation approach, in the modulation of brainstem activity and connectivity in migraine patients. We applied 3T-functional magnetic resonance imaging with improved in-plane spatial resolution (2.62 × 2.62 mm) in episodic migraine (interictal) and age- and sex-matched healthy controls to evaluate brain response to RAVANS (gated to either inhalation or exhalation) and sham stimulation. We further investigated RAVANS modulation of tactile trigeminal sensory afference response in the brainstem using air-puff stimulation directed to the forehead during functional magnetic resonance imaging. Compared with sham and inhalatory-gated RAVANS (iRAVANS), exhalatory-gated RAVANS (eRAVANS) activated an ipsilateral pontomedullary region consistent with nucleus tractus solitarii (NTS). During eRAVANS, NTS connectivity was increased to anterior insula and anterior midcingulate cortex, compared with both sham and iRAVANS, in migraine patients. Increased connectivity was inversely correlated with relative time to the next migraine attack, suggesting clinical relevance to this change in connectivity. Poststimulation effects were also noted immediately after eRAVANS, as we found increased activation in putative pontine serotonergic (ie, nucleus raphe centralis) and noradrenergic (ie, locus coeruleus) nuclei in response to trigeminal sensory afference. Regulation of activity and connectivity of brainstem and cortical regions involved in serotonergic and noradrenergic regulation and pain modulation may constitute an underlying mechanism supporting beneficial clinical outcomes for eRAVANS applied for episodic migraine.

Evoked Pain Analgesia in Chronic Pelvic Pain Patients Using Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation

Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS. Counterbalanced, crossover study. Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation. RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2). Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain.