Human intracranial recordings reveal distinct cortical activity patterns during invasive and non-invasive vagus nerve stimulation

AbstractVagus nerve stimulation (VNS) is being used increasingly to treat a wide array of diseases and disorders. This growth is driven in part by the putative ability to stimulate the nerve non-invasively. Despite decades of use and a rapidly expanding application space, we lack a complete understanding of the acute effects of VNS on human cortical neurophysiology. Here, we investigated cortical responses to sub-perceptual threshold cervical implanted (iVNS) and transcutaneous auricular (taVNS) vagus nerve stimulation using intracranial neurophysiological recordings in human epilepsy patients. To understand the areas that are modulated by VNS and how they differ depending on invasiveness and stimulation parameters, we compared VNS-evoked neural activity across a range of stimulation modalities, frequencies, and amplitudes. Using comparable stimulation parameters, both iVNS and taVNS caused subtle changes in low-frequency power across broad cortical networks, which were not the same across modalities and were highly variable across participants. However, within at least some individuals, it may be possible to elicit similar responses across modalities using distinct sets of stimulation parameters. These results demonstrate that both invasive and non-invasive VNS cause evoked changes in activity across a set of highly distributed cortical networks that are relevant to a diverse array of clinical, rehabilitative, and enhancement applications.

Download Full-text

A Review of Parameter Settings for Invasive and Non-invasive Vagus Nerve Stimulation (VNS) Applied in Neurological and Psychiatric Disorders

Frontiers in Neuroscience ◽

10.3389/fnins.2021.709436 ◽

2021 ◽

Vol 15 ◽

Author(s):

Sean L. Thompson ◽

Georgia H. O’Leary ◽

Christopher W. Austelle ◽

Elise Gruber ◽

Alex T. Kahn ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Past Century ◽

Motor Rehabilitation ◽

Non Invasive ◽

The Past ◽

Stimulation Parameters ◽

History Of ◽

Resistant Depression

Vagus nerve stimulation (VNS) is an established form of neuromodulation with a long history of promising applications. Earliest reports of VNS in the literature date to the late 1800’s in experiments conducted by Dr. James Corning. Over the past century, both invasive and non-invasive VNS have demonstrated promise in treating a variety of disorders, including epilepsy, depression, and post-stroke motor rehabilitation. As VNS continues to rapidly grow in popularity and application, the field generally lacks a consensus on optimum stimulation parameters. Stimulation parameters have a significant impact on the efficacy of neuromodulation, and here we will describe the longitudinal evolution of VNS parameters in the following categorical progression: (1) animal models, (2) epilepsy, (3) treatment resistant depression, (4) neuroplasticity and rehabilitation, and (5) transcutaneous auricular VNS (taVNS). We additionally offer a historical perspective of the various applications and summarize the range and most commonly used parameters in over 130 implanted and non-invasive VNS studies over five applications.

Download Full-text

Long Term Effects of Low Frequency (10 Hz) Vagus Nerve Stimulation on EEG and Heart Rate Variability in Crohn's Disease: A Case Report

Brain Stimulation ◽

10.1016/j.brs.2014.08.001 ◽

2014 ◽

Vol 7 (6) ◽

pp. 914-916 ◽

Cited By ~ 26

Author(s):

Didier Clarençon ◽

Sonia Pellissier ◽

Valérie Sinniger ◽

Astrid Kibleur ◽

Dominique Hoffman ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Crohn’S Disease ◽

Case Report ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Low Frequency ◽

Long Term Effects

Download Full-text

Non-invasive vagus nerve stimulation reduced neuron-derived IL-1β and neuroinflammation in acute ischemic rat brain

Hemorrhagic Stroke ◽

10.1016/j.hest.2021.06.003 ◽

2021 ◽

Author(s):

Lisa Y Yang ◽

Kiran Bhaskar ◽

Jeffrey Thompson ◽

Kelsey Duval ◽

Michel Torbey ◽

...

Keyword(s):

Vagus Nerve ◽

Rat Brain ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Non Invasive

Download Full-text

Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion

Psychological Medicine ◽

10.1017/s0033291720005073 ◽

2021 ◽

pp. 1-11

Author(s):

Magdalena Ferstl ◽

Vanessa Teckentrup ◽

Wy Ming Lin ◽

Franziska Kräutlein ◽

Anne Kühnel ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Positive Mood ◽

Credible Interval ◽

Cognitive Effort ◽

Mood States ◽

Non Invasive ◽

Lower Baseline ◽

Open Question

Abstract Background Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. Methods Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings. Results We found that 90 min of either left-sided or right-sided taVNS improved positive mood [b = 5.11, 95% credible interval, CI (1.39–9.01), 9.6% improvement relative to the mood intercept, BF10 = 7.69, pLME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [r = −0.42, 95% CI (−0.58 to −0.21), BF10 = 249]. Conclusions We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.

Download Full-text

Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study

The Journal of Headache and Pain ◽

10.1186/s10194-016-0684-z ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 34

Author(s):

Licia Grazzi ◽

Gabriella Egeo ◽

Anne H. Calhoun ◽

Candace K. McClure ◽

Eric Liebler ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Menstrually Related Migraine ◽

Non Invasive

Download Full-text

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

Cephalalgia ◽

10.1177/0333102417717470 ◽

2017 ◽

Vol 37 (13) ◽

pp. 1285-1293 ◽

Cited By ~ 46

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.

Download Full-text

Non-invasive vagus nerve stimulation for treatment of cluster headache: a retrospective review of prescribing in England

British Journal of Healthcare Management ◽

10.12968/bjhc.2021.0126 ◽

2021 ◽

pp. 1-11

Author(s):

Nicholas Silver ◽

Carl Bradley ◽

Rebecca Stuckey ◽

Madeleine Murphy ◽

Fiona Greenwood ◽

...

Keyword(s):

Cluster Headache ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Non Invasive ◽

Innovation And Technology ◽

Prescription Refill ◽

Collection Period ◽

Continued Use ◽

Clinical Audits

Background/Aims Beginning in April 2019, non-invasive vagus nerve stimulation was included in the NHS Innovation and Technology Payment programme. The programme guaranteed reimbursement of at least a 3-month course of treatment using gammaCore, through a prescription refill card, authorised by a headache specialist for patients with cluster headache who reported a clinically meaningful benefit. This study evaluated prescribing and refill trends to assess the use of gammaCore in England since the beginning of this programme. Methods Data regarding gammaCore prescriptions and refills from 1 April 2019 to 31 December 2020 were collected and tabulated. Patients were categorised into three groups: those who initiated gammaCore therapy under the programme (new starters), those who were prescribed ≥1 refill, and those who were prescribed ≥2 refills. One refill corresponds to 3 months of gammaCore therapy. Results In total, 52 NHS sites submitted 2092 prescriptions for gammaCore devices, including 655 for new starters. Among new starters, 46.3% received ≥1 refill and 30.9% received ≥2 refills. Those who started using gammaCore after its inclusion in the Innovation and Technology Payment programme received up to seven refills during the data collection period, representing 21 months of therapy. Conclusions This is one of the largest clinical audits of patients with cluster headache. Patients' continued use of gammaCore treatment through multiple 3-month refills in this audit suggests that non-invasive vagus nerve stimulation is efficacious, tolerable and practical for patients with cluster headache.

Download Full-text

Non-invasive Autonomic Neuromodulation Is Opening New Landscapes for Cardiovascular Diseases

Frontiers in Physiology ◽

10.3389/fphys.2020.550578 ◽

2020 ◽

Vol 11 ◽

Author(s):

Mingxian Chen ◽

Songyun Wang ◽

Xuping Li ◽

Lilei Yu ◽

Hui Yang ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Light Emitting Diode ◽

Heart Diseases ◽

Bipolar Electrode ◽

Light Emitting ◽

Non Invasive ◽

Emerging Therapies

Autonomic imbalance plays a crucial role in the genesis and maintenance of cardiac disorders. Approaches to maintain sympatho-vagal balance in heart diseases have gained great interest in recent years. Emerging therapies However, certain types of emerging therapies including direct electrical stimulation and nerve denervation require invasive implantation of a generator and a bipolar electrode subcutaneously or result in autonomic nervous system (ANS) damage, inevitably increasing the risk of complications. More recently, non-invasive neuromodulation approaches have received great interest in ANS modulation. Non-invasive approaches have opened new fields in the treatment of cardiovascular diseases. Herein, we will review the protective roles of non-invasive neuromodulation techniques in heart diseases, including transcutaneous auricular vagus nerve stimulation, electromagnetic field stimulation, ultrasound stimulation, autonomic modulation in optogenetics, and light-emitting diode and transcutaneous cervical vagus nerve stimulation (gammaCore).

Download Full-text

Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis

10.1101/2021.01.18.426704 ◽

2021 ◽

Cited By ~ 1

Author(s):

Vinzent Wolf ◽

Anne Kühnel ◽

Vanessa Teckentrup ◽

Julian Koenig ◽

Nils B. Kroemer

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Vagus Nerve ◽

Brain Stimulation ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Meta Analysis ◽

Current Evidence ◽

Beneficial Effects ◽

Non Invasive

AbstractNon-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. Here, we perform a living Bayesian random effects meta-analysis to synthesize the current evidence concerning the effects of taVNS on heart rate variability (HRV), a candidate biomarker that has, so far, received most attention in the field. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 17 single-blind studies comparing taVNS versus sham in healthy participants. These newly synthesized results provide strong evidence for the null hypothesis (g = 0.011, CIshortest = [−0.103, 0.125], BF01 = 25.587), indicating that acute taVNS does not alter HRV compared to sham. To conclude, based on a synthesis of the available evidence to date, there is no support for the hypothesis that HRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, we believe that the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.

Download Full-text