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 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.

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 Brain signaling dynamics after vagus nerve stimulation

2021 ◽  
Author(s):  
Vanessa Teckentrup ◽  
Marina Krylova ◽  
Hamidreza Jamalabadi ◽  
Sandra Neubert ◽  
Monja P. Neuser ◽  
...  
Keyword(s):  
Time Series ◽  
Functional Connectivity ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Neural Circuit ◽  
Future Research ◽  
Dynamic Functional Connectivity ◽  
Wide Range ◽  
Induced Changes

The vagus nerve projects to a well-defined neural circuit via the nucleus tractus solitarii (NTS) and its stimulation elicits a wide range of metabolic, neuromodulatory, and behavioral effects. Transcutaneous vagus nerve stimulation (tVNS) has been established as a promising technique to non-invasively alter brain function. However, the precise dynamics elicited by tVNS in humans are still largely unknown. Here, we performed fMRI with concurrent right-sided tVNS (vs. sham) following a randomized cross-over design (N=40). First, to unravel the temporal profile of tVNS-induced changes in the NTS, we compared fMRI time series to canonical profiles for stimulation ON and OFF cycles. Model comparisons indicated that NTS time series were best fit by block-wise shifts in signal amplitude with stimulation ON and OFF estimates being highly correlated. Therefore, we compared stimulation (ON + OFF) versus baseline phases and found that tVNS increased fMRI BOLD activation in the NTS, but this effect was dependent on sufficient temporal signal-to-noise ratio (tSNR) in the mask. Second, to identify the spatiotemporal evolution of tVNS-induced changes in the brain, we examined lagged co-activation patterns and phase coherence. In contrast to our hypothesis, tVNS did not alter dynamic functional connectivity after correction for multiple comparisons. Third, to establish a positive control for future research, we measured changes in gastric myoelectrical frequency via an electrogastrogram. Again, in contrast to our hypothesis, tVNS induced no changes in gastric frequency. Collectively, our study provides evidence that tVNS can perturb brain signaling in the NTS, but these effects are dependent on tSNR and require precise localization. In light of an absence of acute tVNS-induced effects on dynamic functional connectivity and gastric motility, we discuss which steps are necessary to advance future research on afferent and efferent effects of tVNS.

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.

scholarly journals The Instant Effects of Continuous Transcutaneous Auricular Vagus Nerve Stimulation at Acupoints on the Functional Connectivity of Amygdala in Migraine without Aura: A Preliminary Study

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wenting Luo ◽  
Yue Zhang ◽  
Zhaoxian Yan ◽  
Xian Liu ◽  
Xiaoyan Hou ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Random Order ◽  
Brain Regions ◽  
Vital Role ◽  
Auricular Acupuncture ◽  
Fmri Study ◽  
The Right ◽  
Episodic Migraineurs

Background. A growing body of evidence suggests that both auricular acupuncture and transcutaneous auricular vagus nerve stimulation (taVNS) can induce antinociception and relieve symptoms of migraine. However, their instant effects and central treatment mechanism remain unclear. Many studies proved that the amygdalae play a vital role not only in emotion modulation but also in pain processing. In this study, we investigated the modulation effects of continuous taVNS at acupoints on the FC of the bilateral amygdalae in MwoA. Methods. Thirty episodic migraineurs were recruited for the single-blind, crossover functional magnetic resonance imaging (fMRI) study. Each participant attended two kinds of eight-minute stimulations, taVNS and sham-taVNS (staVNS), separated by seven days in random order. Finally, 27 of them were included in the analysis of seed-to-voxel FC with the left/right amygdala as seeds. Results. Compared with staVNS, the FC decreased during taVNS between the left amygdala and left middle frontal gyrus (MFG), left dorsolateral superior frontal gyrus, right supplementary motor area (SMA), bilateral paracentral lobules, bilateral postcingulum gyrus, and right frontal superior medial gyrus, so did the FC of the right amygdala and left MFG. A significant positive correlation was observed between the FC of the left amygdala and right SMA and the frequency/total time of migraine attacks during the preceding four weeks. Conclusion. Continuous taVNS at acupoints can modulate the FC between the bilateral amygdalae and pain-related brain regions in MwoA, involving the limbic system, default mode network, and pain matrix, with obvious differences between the left amygdala and the right amygdala. The taVNS may produce treatment effects by modulating the abnormal FC of the amygdala and pain networks, possibly having the same central mechanism as auricular acupuncture.

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