scholarly journals Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

2015 ◽  
Vol 309 (10) ◽  
pp. H1740-H1752 ◽  
Author(s):  
Jeffrey L. Ardell ◽  
Pradeep S. Rajendran ◽  
Heath A. Nier ◽  
Bruce H. KenKnight ◽  
J. Andrew Armour
Keyword(s):  
Cardiac Function ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Vagal Afferents ◽  
Intact State ◽  
Mediated Effects ◽  
Functional Consequences ◽  
Anesthetized Dogs ◽  
The Right

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy.

scholarly journals Effect of defibrillation on the performance of an implantable vagus nerve stimulation system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Imad Libbus ◽  
Scott R. Stubbs ◽  
Scott T. Mazar ◽  
Scott Mindrebo ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Pulse Generator ◽  
High Energy ◽  
Implantable Pulse Generator ◽  
Defibrillation Pulse ◽  
Stimulation System

Abstract Background Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. Methods DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. Results The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. Conclusions Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

scholarly journals Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: An electrophysiological study in healthy volunteers

Cephalalgia ◽  
2017 ◽  
Vol 37 (13) ◽  
pp. 1285-1293 ◽  
Author(s):  
Romain Nonis ◽  
Kevin D’Ostilio ◽  
Jean Schoenen ◽  
Delphine Magis
Keyword(s):  
Vagus Nerve ◽  
Healthy Volunteers ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Electrophysiological Study ◽  
Vagal Afferents ◽  
Response Analysis ◽  
Bipolar Electrode ◽  
Non Invasive ◽  
Vagal Afferent

Background Benefits of cervical non-invasive vagus nerve stimulation (nVNS) devices have been shown in episodic cluster headache and preliminarily suggested in migraine, but direct evidence of vagus nerve activation using such devices is lacking. Vagal somatosensory evoked potentials (vSEPs) associated with vagal afferent activation have been reported for invasive vagus nerve stimulation (iVNS) and non-invasive auricular vagal stimulation. Here, we aimed to show and characterise vSEPs for cervical nVNS. Methods vSEPs were recorded for 12 healthy volunteers who received nVNS over the cervical vagus nerve, bipolar electrode/DS7A stimulation over the inner tragus, and nVNS over the sternocleidomastoid (SCM) muscle. We measured peak-to-peak amplitudes (P1-N1), wave latencies, and N1 area under the curve. Results P1-N1 vSEPs were observed for cervical nVNS (11/12) and auricular stimulation (9/12), with latencies similar to those described previously, whereas SCM stimulation revealed only a muscle artefact with a much longer latency. A dose-response analysis showed that cervical nVNS elicited a clear vSEP response in more than 80% of the participants using an intensity of 15 V. Conclusion Cervical nVNS can activate vagal afferent fibres, as evidenced by the recording of far-field vSEPs similar to those seen with iVNS and non-invasive auricular stimulation.

Noninvasive vagus nerve stimulation and the trigeminal autonomic reflex

Neurology ◽  
2020 ◽  
Vol 94 (10) ◽  
pp. e1085-e1093 ◽  
Author(s):  
Maike Möller ◽  
Jan Mehnert ◽  
Celina F. Schroeder ◽  
Arne May
Keyword(s):  
Functional Connectivity ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Parahippocampal Gyrus ◽  
Pontine Nucleus ◽  
Fmri Session ◽  
Autonomic Reflex ◽  
The Right ◽  
Healthy Participants

ObjectiveThe trigeminal autonomic reflex is a physiologic reflex that plays a crucial role in primary headache and particularly in trigeminal autonomic cephalalgias, such as cluster headache. Previous studies have shown that this reflex can be modulated by the vagus nerve, leading to an inhibition of the parasympathetic output of the reflex in healthy participants. The aim of the present study was to characterize neural correlates of the modulatory effect of noninvasive vagus nerve stimulation (nVNS) on the trigeminal autonomic reflex.MethodsTwenty-one healthy participants were included in a 2-day, randomized, single-blind, within-subject design. The reflex was activated inside the MRI scanner using kinetic oscillation stimulation placed in the left nostril, resulting in an increase in lacrimation. After the first fMRI session, the participants received either sham vagus nerve stimulation or nVNS outside the scanner and underwent a subsequent fMRI session.ResultsnVNS prompted an increase in activation of the left pontine nucleus and a decreased activation of the right parahippocampal gyrus. Psychophysiologic interaction analyses revealed an increased functional connectivity between the left pontine nucleus and the right hypothalamus and a decreased functional connectivity between the right parahippocampal gyrus and the bilateral spinal trigeminal nuclei (sTN).ConclusionsThese findings indicate a complex network involved in the modulatory effect of nVNS including the hypothalamus, the sTN, the pontine nucleus, and the parahippocampal gyrus.

scholarly journals Implantable vagus nerve stimulation system performance is not affected by internal or external defibrillation shocks

2021 ◽  
Author(s):  
Imad Libbus ◽  
Scott R. Stubbs ◽  
Scott T. Mazar ◽  
Scott Mindrebo ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
System Performance ◽  
Vagus Nerve Stimulation ◽  
Pulse Generator ◽  
High Energy ◽  
Cardioverter Defibrillator ◽  
Histologic Evaluation ◽  
The Right

Abstract Purpose Autonomic regulation therapy (ART) for heart failure (HF) is delivered using vagus nerve stimulation (VNS), and has been associated with improvement in cardiac function and HF symptoms. VNS is delivered using an implantable pulse generator (IPG) and a lead placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on VNS system performance. Methods Normal swine (n = 4) with VNS system implants on the right cervical vagus nerve received sequential defibrillation shocks with three defibrillation systems: an implantable cardioverter defibrillator (ICD), a subcutaneous ICD (S-ICD), and an external cardioverter defibrillator (ECD). Each system delivered a series of bipolar high-energy shocks and reverse-polarity high-energy shocks. Results The specified cardiac defibrillation shocks were delivered successfully from each of the three defibrillation systems to all animals. After each shock series, interrogation of the IPG confirmed that software and data were unchanged from pre-programmed values. After all of the defibrillation shocks were delivered, the IPGs underwent and passed comprehensive electrical testing demonstrating proper system function. No shifts in IPG parameters or ART system failures were observed, and histologic evaluation of the vagus nerve revealed no anatomic changes. Conclusions Implantable VNS systems were tested in vivo for immunity to defibrillation via ICD, S-ICD, and ECD, and were found to be unaffected by a series of high-energy defibrillation shocks. These results confirm that ART systems are capable of continuing to function after defibrillation and the cervical vagus nerve is anatomically unaffected.

scholarly journals Self-Administration of Right Vagus Nerve Stimulation Activates Midbrain Dopaminergic Nuclei

2021 ◽  
Vol 15 ◽  
Author(s):  
Jackson Brougher ◽  
Umaymah Aziz ◽  
Nikitha Adari ◽  
Muskaan Chaturvedi ◽  
Aryela Jules ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Substantia Nigra Pars Compacta ◽  
Future Research ◽  
Vagus Nerves ◽  
Self Administration ◽  
Cervical Nerve ◽  
Fos Expression ◽  
The Right

Background: Left cervical vagus nerve stimulation (l-VNS) is an FDA-approved treatment for neurological disorders including epilepsy, major depressive disorder, and stroke, and l-VNS is increasingly under investigation for a range of other neurological indications. Traditional l-VNS is thought to induce therapeutic neuroplasticity in part through the coordinated activation of multiple broadly projecting neuromodulatory systems in the brain. Recently, it has been reported that striking lateralization exists in the anatomical and functional connectivity between the vagus nerves and the dopaminergic midbrain. These emerging findings suggest that VNS-driven activation of this important plasticity-promoting neuromodulatory system may be preferentially driven by targeting the right, rather than the left, cervical nerve.Objective: To compare the effects of right cervical VNS (r-VNS) vs. traditional l-VNS on self-administration behavior and midbrain dopaminergic activation in rats.Methods: Rats were implanted with a stimulating cuff electrode targeting either the right or left cervical vagus nerve. After surgical recovery, rats underwent a VNS self-administration assay in which lever pressing was paired with r-VNS or l-VNS delivery. Self-administration was followed by extinction, cue-only reinstatement, and stimulation reinstatement sessions. Rats were sacrificed 90 min after completion of behavioral training, and brains were removed for immunohistochemical analysis of c-Fos expression in the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as in the noradrenergic locus coeruleus (LC).Results: Rats in the r-VNS cohort performed significantly more lever presses throughout self-administration and reinstatement sessions than did rats in the l-VNS cohort. Moreover, this appetitive behavioral responding was associated with significantly greater c-Fos expression among neuronal populations within the VTA, SNc, and LC. Differential c-Fos expression following r-VNS vs. l-VNS was particularly prominent within dopaminergic midbrain neurons.Conclusion: Our results support the existence of strong lateralization within vagal-mesencephalic signaling pathways, and suggest that VNS targeted to the right, rather than left, cervical nerve preferentially activates the midbrain dopaminergic system. These findings raise the possibility that r-VNS could provide a promising strategy for enhancing dopamine-dependent neuroplasticity, opening broad avenues for future research into the efficacy and safety of r-VNS in the treatment of neurological disease.

scholarly journals Vagus nerve stimulation increases vigor to work for rewards

2019 ◽  
Author(s):  
Monja P. Neuser ◽  
Vanessa Teckentrup ◽  
Anne Kühnel ◽  
Manfred Hallschmid ◽  
Martin Walter ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Bayes Factor ◽  
Vital Role ◽  
Non Invasive ◽  
Reward Seeking ◽  
Monetary Rewards ◽  
Reducing Costs ◽  
The Right

AbstractInteroceptive feedback transmitted via the vagus nerve plays a vital role in motivation by tuning actions according to physiological needs. Whereas vagus nerve stimulation (VNS) reinforces actions and enhances dopamine transmission in animals, motivational effects elicited by VNS in humans are still largely elusive. Here, we applied non-invasive transcutaneous auricular VNS (taVNS) on the left or the right ear using a randomized cross-over design (vs. sham). During stimulation, 81 healthy participants had to exert effort to earn food or monetary rewards. We reasoned that taVNS enhances motivation and tested whether it does so by increasing prospective benefits (i.e., vigor) or reducing costs of action (i.e., maintenance) compared to sham stimulation. In line with preclinical studies, taVNS generally enhanced invigoration of effort (p = .004, Bayes factor, BF10 = 7.34), whereas stimulation on the left side primarily facilitated vigor for food rewards (left taVNS: Stimulation × Reward Type, p =.003, BF10 = 11.80). In contrast, taVNS did not affect effort maintenance (ps ≥ .09, BF10 < 0.52). Critically, during taVNS, vigor declined less steeply with decreases in wanting (Δb = −.046, p = .031) indicating a boost in the drive to work for rewards. Collectively, our results suggest that taVNS enhances reward-seeking by boosting vigor, not effort maintenance and that the side of the stimulation affects generalization beyond food reward. We conclude that taVNS may enhance the pursuit of prospective rewards which may pave new avenues for treatment of motivational deficiencies.

scholarly journals Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction

2015 ◽  
Vol 309 (7) ◽  
pp. H1198-H1206 ◽  
Author(s):  
Eric Beaumont ◽  
Elizabeth M. Southerland ◽  
Jean C. Hardwick ◽  
Gary L. Wright ◽  
Shannon Ryan ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Neuronal Excitability ◽  
Cardiac Tissue ◽  
Input Resistance ◽  
Left Ventricular ◽  
Systolic Volume ◽  
End Systolic Volume ◽  
The Right

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls ( n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% ( P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% ( P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls ( P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls ( P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls ( P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein ( P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions.

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