Posts Tagged VNS

[Infographic] What to Expect During VNS Implantation

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[Research] Vagal nerve stimulation may improve post-stroke motor recovery

The Vagus Nerve Stimulation (VNS) may promote reorganization of motor networks via engaging a variety of molecular and neuronal mechanisms through ascending neuromodulatory systems. A recently published review from Frontiers in Neuroscience (N.D. Engineer et al. Targeted Vagus nerve stimulation for rehabilitation after stroke, Front Neurosci. 2019, 29;13:280) has laid out how recent experimental and clinical studies are providing increasing evidence for a beneficial effect of vagus nerve stimulation for the motor recovery after stroke of both, ischemic and hemorrhagic origin. Two multi-site, randomized controlled pilot trials have suggested that when paired with neurorehabilitation, VNS stimulation may generate temporally precise neuromodulatory feedback within the synaptic eligibility trace and may hence, drive synaptic plasticity.

  1. A single-blinded, randomized feasibility study evaluating VNS paired with motor rehabilitation was performed by Dawson et al. (2016) in 20 participants > 6 months after ischemic stroke who had moderate to severe upper limb weakness. Subjects were randomized to VNS paired with rehabilitation (n = 9; implanted) or rehabilitation alone (n = 11; not implanted). VNS was triggered by a physiotherapist pushing a button during task-specific movements. The main outcome measures were a change in upper extremity Fugl-Meyer Assessment (FMAUE) score and response rate – FMA-UE change _6 points was considered clinically meaningful. After 6 weeks of in-clinic rehabilitation, participants in the paired VNS group showed a 9.6-point improvement from baseline while the control group improved by 3 points in the per-protocol analysis (between group difference = 6.5 points, CI: 0.4 to 12.6, p = 0.038). The response rates were 66 and 36.4% in VNS and control groups, respectively. No serious adverse device effects were reported.
  2. The second study was a multicenter, fully blinded and randomized study (Kimberley et al., 2018). All participants were implanted with the VNS device, which allowed the control group to crossover to receive paired VNS therapy after completion of blinded follow-up. This permitted a within subject comparison of gains. To evaluate the lasting effects of VNS stimulation combined with home-based physiotherapy was included as part of the study. Seventeen participants who had moderate to severe upper extremity impairment after stroke were enrolled at four sites. Both groups had 1 month of at-home exercises with no VNS followed by 2 months of home-based therapy. During home therapy, participants in both groups activated the VNS device at the start of each 30-min session via a magnetswipe over the implanted pulse generator to deliver either Active or Paired VNS (0.8 mA) or Control VNS (0 mA), respectively. After 2 months of home-based therapy, thepaired VNS group continued the VNS therapy while the Control Group switched over to receive paired VNS. After 6 weeks of in-clinic therapy, the FMA-UE score increased by 7.6 points for the VNS group and 5.3 points for controls. Three months after the end of in-clinic therapy (post-90), the FMA-UE increased by 9.5 in the paired VNS group and 3.8 points in controls. At post-90, response rate (FMA-UE change _6 points) was 88% in the VNS group and 33% in controls (p = 0.03).

Noteworthy in both studies seemed the greater improvement of the upper limb function when physiotherapy was applied simultaneously with vagal nerve stimulation. VNS likely supported the recovery of upper limb functions via activation of multiple neuromodulatory networks that regulate synaptic plasticity. This may include the noradrenergic, cholinergic, and serotonergic systems (Nichols et al., 2011; Hulsey et al., 2017). These neuromodulators, in turn, act synergistically to alter spike-timing dependent plasticity (STDP) properties in active networks. The studies above align well with the time scale of the synaptic eligibility trace. VNS may drive temporally precise neuromodulatory release to reinforce ongoing neural activity related to the therapeutic event. An open question is whether similar improvement can be achieved using non-invasive vagal nerve stimulation. To this moment, the identifying and consistently delivering stimulation within a particular range of parameters appears to be of greater challenge with non-invasive VNS than with the implanted VNS device.

Physiotherapy combined with vagal nerve stimulation seems to be a new and promising approach to enhance the functional recovery after stroke.

Key points:

  • Vagus Nerve Stimulation (VNS) may promote reorganization of motor networks
  • Experimental and clinical studies pointed towards a beneficial effect for the motor recovery after stroke
  • VNS may drive temporally precise neuromodulatory release to reinforce ongoing neural activity

References:

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke. https://www.ncbi.nlm.nih.gov/pubmed/30983963

 

via Vagal nerve stimulation may improve post-stroke motor recovery

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[ARTICLE] An Exploratory Study of Predictors of Response to Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Ischemic Stroke – Full Text

Abstract

We have previously shown the safety and feasibility of vagus nerve stimulation (VNS) paired with upper-limb rehabilitation after ischemic stroke. In this exploratory study, we assessed whether clinical and brain MRI variables predict response to treatment. We used data from two completed randomised and blinded clinical trials (N = 35). All participants had moderate to severe upper-limb weakness and were randomised to 6-weeks intensive physiotherapy with or without VNS. Participants had 3 T brain MRI at baseline. The primary outcome was change in Fugl-Meyer Assessment, upper-extremity score (FMA-UE) from baseline to the first day after therapy completion. We used general linear regression to identify clinical and brain MRI predictors of change in FMA-UE. VNS-treated participants had greater improvement in FMA-UE at day-1 post therapy than controls (8.63 ± 5.02 versus 3.79 ± 5.04 points, t = 2.83, Cohen’s d = 0.96, P = 0.008). Higher cerebrospinal fluid volume was associated with less improvement in FMA-UE in the control but not VNS group. This was also true for white matter hyperintensity volume but not after removal of an outlying participant from the control group. Responders in the VNS group had more severe arm impairment at baseline than responders to control. A phase III trial is now underway to formally determine whether VNS improves outcomes and will explore whether these differ in people with more severe baseline upper-limb disability and cerebrovascular disease.

Introduction

Vagus nerve stimulation (VNS) paired with upper-limb rehabilitation is a potential novel treatment for arm weakness after stroke. VNS triggers release of plasticity promoting neuromodulators, such as acetylcholine and norepinephrine, throughout the cortex1. Timing this with motor training drives task-specific plasticity in the motor cortex2 and VNS paired with rehabilitative training has been shown to improve recovery in different preclinical models of stroke, both in comparison to VNS alone and rehabilitation alone3,4. These improvements were associated with synaptic reorganization of cortical motor networks and recruitment of residual motor neurons controlling the impaired forelimb5. Two clinical studies comparing VNS paired with upper-limb rehabilitation with upper-limb rehabilitation alone have shown it to be acceptably safe and feasible and that it may improve arm weakness after ischemic stroke6,7.

Arm weakness is the most common symptom of stroke and approximately half of stroke survivors with arm weakness have prolonged disability, which is associated with reduced quality of life8,9. Restoration of arm function after stroke is a priority for many stroke survivors10. However, recovery of motor function after stroke varies, so identifying factors that help predict response is important to aid patient selection and identify those most likely to respond. This is particularly true where therapies are invasive (involving surgery) and/or time consuming; VNS requires implantation of a nerve stimulator which is costly and associated with risks of anaesthesia, a small risk of infection and small risk of vocal cord palsy. There are several clinical and brain imaging markers that predict cognitive and functional recovery after stroke including age, level of impairment, white matter hyperintensity (WMH) volume, stroke lesion volume, corticospinal tract damage and blood pressure level11,12,13.

In the present study, we combined clinical and brain magnetic resonance imaging (MRI) data from our two previous randomised trials of VNS paired with rehabilitation for the upper-limb after ischemic stroke6,7. We performed exploratory analyses to assess predictors of response to VNS paired with upper-limb rehabilitation. Our goal was to identify predictive factors for further study that may help with patient selection for this promising novel therapy. […]

 

Continue —->  An Exploratory Study of Predictors of Response to Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Ischemic Stroke | Scientific Reports

figure1

Illustration of brain MRI measures obtained. (A) Raw FLAIR image. (B) Segmentation of white matter hyperintensities (WMH; bright red) and ischaemic stroke infarct volumes (royal blue). (C) Estimate of the left (cyan) and right (pink) corticospinal tracts. (D) Interaction between stroke lesion (dull red) and corticospinal tract (light blue) in a 3D rendering. Images A and B come from the same patient, C and D are from separate patients and all are shown in neurological (“left is left”) convention.

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[WEB SITE] Depression Overview: Emotional Symptoms, Physical Signs, and More – WebMD

via Depression Overview: Emotional Symptoms, Physical Signs, and More

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[BLOG POST] Mozart and epilepsy: the rhythm beats on

 

I can’t seem to get away from the theme of Mozart and epilepsy. When I first looked at this, in a blog post titled Mozart and seizures? The links between epilepsy and music, I took the topic rather lightly, more a subscript than a headline you may say. But I have since learnt to take the links between epilepsy and music more seriously.

By Barbara Krafft – The Bridgeman Art Library, Object 574471, Public Domain, Link

 

The major trigger for my ‘road to Damascus’ conversion is a 2018 paper titled Study of the Mozart effect in children with epileptic electroencephalograms, published in the journal Seizure. The paper was an eye-opener because it gave a very helpful comprehensive context to the broader beneficial effect of music…not just in epilepsy, but in other neurological disorders such as Parkinson’s diseasedementia and sleep disordersThe authors, Elyza Grylls and colleagues, started on the established premise that Mozart’s music has a beneficial effect on epilepsy. What they wanted to know was if other forms of music have a similar settling effect on epilepsy, or if only Mozart’s music carries the magic touch. The authors therefore played Mozart’s Sonata for two pianos in D major (K448) to 40 children with epilepsy who were undergoing an EEG (electroencephalogram, or electrical brain wave test). They then compared this with the effect of playing other types of music. Remarkably, they found that only Mozart’s Sonata led to a significant reduction in EEG epileptic discharges.

Public Domain, Link

The authors concluded that there was indeed an anti-epileptic effect of Mozart’s music, the so-called  ‘Mozart therapy’. But what is so special about K448? They speculate that it has to do with the structure of Mozart’s music, containing as it does, long periodicities. Interestingly, the music of Yanni, which is similarly structured, has somewhat a similar effect on brain wave activity. On the contrary, and sorry to Beethoven fans, Fur Elise doesn’t have this effect.

By W.J. Baker (held the expired copyright on the photograph) – Library of Congress[1]Contrairement à une erreur fréquemment répandue le buste a été réalisé par Hugo Hagen, non pas à partir du masque mortuaire mais, comme de nombreux autres, d’après le masque réalisé en 1812 par Franz Klein pour un buste qu’il devait réaliser ensuite., Public Domain, Link

So what does the structure of Mozart’s music do to the brain? One suggestion is that Mozart’s music enhances the body’s parasympathetic drive; this reduces the heart rate, and thereby inhibits the brain’s propensity to epileptic seizures. The suppression of this parasympathetic drive is of course the theory behind using vagus nerve stimulation (VNS) to treat drug-resistant epilepsy. For more on VNS, see my previous blog, Vagus nerve stimulation: from neurology and beyond!

By Bionerd – MRI at Charite Mitte, Berlin (used with permission), CC BY 3.0Link

You have surely wondered by now if K448 is the only one of Mozart’s compositions to have an anti-epileptic effect. It doesn’t matter if you have not, because the authors of another interesting paper did. They titled their study, published in 2018, Mozart’s music in children with drug-refractory epileptic encephalopathies: comparison of two protocols. Published in the journal Epilepsy and Behaviour, the authors, Giangennaro Coppola and colleagues, compared the effect of K448 with a set of his other compositions. Intriguingly they found that the composition set actually had a greater effect in epilepsy than K448…by a wide margin of 70% to 20%! Furthermore, the set was better tolerated by the children; they were less irritable and had a better nighttime sleep quality.   

https://www.publicdomainpictures.net/en/view-image.php?image=76907&picture=dog-amp-child-painting

It therefore appears as if it all rosy in the garden of music and the brain. But it is not! As every rose grows on a thorny tree, so do some forms of music trigger epileptic seizures. This so-called musicogenic epilepsy is well-recognised, and two recent culprits are the music of Sean Paul, discussed in the journal Scientific American , and the music of Ne Yo, explored by NME. Therefore you should craft your playlist wisely.

By CLASSICNEYO – Own workCC BY-SA 4.0Link

So, is it time for neurologists to start prescribing music?

Or is it too much of a double-edged sword?

Music is #SimplyIrresistible. Luca Florio on Flickr. https://www.flickr.com/photos/elle_florio/29516744480

via Mozart and epilepsy: the rhythm beats on – The Neurology Lounge

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[Abstract] Combining Transcutaneous Vagus Nerve Stimulation and Upper-Limb Robotic Rehabilitation in Chronic Stroke Patients

Introduction And Aims: Vagus nerve stimulation (VNS) is a promising approach for enhancing rehabilitation effects in stroke patients, but the invasiveness of this technique reduces its clinical application. Recently, a non-invasive technique for stimulating vagus nerve has been developed. We evaluated safety, feasibility, and efficacy of noninvasive VNS combined with robotic rehabilitation for improving upper limb functionality in chronic stroke.

First page of article

via Combining Transcutaneous Vagus Nerve Stimulation and Upper-Limb Robotic Rehabilitation in Chronic Stroke Patients – Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation

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[WEB SITE] Enhanced rehab for stroke doubles movement recovery.

Date: September 27, 2018

Source: University of Texas at Dallas

Summary: A novel therapy technique has been shown in a pilot study to double the rate of upper limb recovery in stroke patients, a leap forward in treating the nearly 800,000 Americans who suffer strokes each year.

FULL STORY

A novel therapy technique invented by researchers at The University of Texas at Dallas has been shown in a pilot study to double the rate of upper limb recovery in stroke patients, a leap forward in treating the nearly 800,000 Americans who suffer strokes each year.

The results of the study, funded by UT Dallas spinoff company MicroTransponder of Austin, Texas, were published Sept. 27 in the journal Stroke.

The findings indicate that targeted plasticity therapy — which involves stimulation of the vagus nerve — paired with traditional motor-skill rehabilitation is not only safe, but also twice as effective as rehab alone.

Dr. Jane Wigginton, the chief medical officer at UT Dallas’ Texas Biomedical Device Center (TxBDC) and an associate professor of emergency medicine at UT Southwestern Medical Center, led the Dallas site of the clinical trial, which involved 17 people across the country who had suffered a stroke.

“Stroke is too common and too debilitating for us to tolerate the status quo,” Wigginton said. “Patients need a real solution so they can get back to fully living their lives.”

Dr. Michael Kilgard, associate director and chief science officer of the TxBDC, invented targeted plasticity therapy (TPT). Kilgard, who is also the Margaret Fonde Jonsson Professor in the School of Behavioral and Brain Sciences (BBS), said the study results further validate the theories that he and his colleagues based their TPT work on beginning in 2009.

“We set out to design an approach that could transform long-term care and restore quality of life to patients for whom that has thus far been impossible,” said Kilgard, who was not involved in the clinical trial. “These results show our method has immense potential. We’re excited about what this could mean for millions of stroke patients worldwide.”

Researchers affiliated with the TxBDC and BBS developed the therapy technique, which pairs physical movements with precisely timed vagus nerve stimulation (VNS) — electrical stimulus of the nerve via a device implanted on the nerve in the neck.

The vagus nerve controls the parasympathetic nervous system, overseeing many unconscious functions such as circulation and digestion. Stimulating the nerve initiates neural plasticity — reorganization of the brain’s circuitry. The idea behind TPT is that synchronizing VNS with movement accelerates plasticity in a damaged brain, and with it, recovery.

A stroke occurs when blood flow to the brain is interrupted because of a blockage or a ruptured blood vessel. Limb mobility can be affected when nerve cells are damaged. Such forms of brain trauma are often treated with rehabilitation that includes repeated movement of the affected limb in an effort to regain motor skills. The approach is thought to work by helping the brain reorganize.

Several studies of Kilgard’s technique in animal models have previously demonstrated that it is effective in recovering limb function after stroke. A small clinical trial in Europe also provided encouraging data for its potential use in humans.

In 2009, UT Dallas licensed its VNS technique as a stroke and tinnitus treatment to MicroTransponder, which sponsored the new double-blind, placebo-controlled study. Neither the researchers nor the study subjects knew who was getting VNS stimulation and who was not.

Each study subject was a stroke patient whose stroke occurred between four months and five years prior to selection. After they had a VNS device implanted, the subjects received six weeks of in-clinic rehab followed by a home exercise program. About half were treated with active VNS while the rest received control VNS. All were assessed one, 30 and 90 days after therapy with a widely used, stroke-specific measure of performance impairment.

In addition to showing that the technique is safe, the researchers found that subjects receiving active VNS scored more than twice as high as control subjects at the 30- and 90-day intervals, opening the way for larger, more extensive clinical trials, Kilgard said. One such trial is in the recruitment phase and includes a study site in Dallas.

Story Source:

Materials provided by University of Texas at DallasNote: Content may be edited for style and length.


Journal Reference:

  1. Teresa J. Kimberley et al. Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke A Blinded Randomized Pilot StudyStroke, 2018 DOI: 10.1161/STROKEAHA.118.022279

 

via Enhanced rehab for stroke doubles movement recovery — ScienceDaily

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[Abstract] Safety, feasibility, and efficacy of transcutaneous vagus nerve stimulation combined with upper-limb robotic rehabilitation after stroke

Abstract

The efficacy of standard rehabilitation for improving upper limb functionality after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) combined with rehabilitation is a promising approach, but the invasiveness of this technique reduces its clinical application. Recently, a non-invasive technique for stimulating vagus nerve has been developed. Aim of this study is to evaluate safety, feasibility, and efficacy of noninvasive VNS combined with robotic rehabilitation for improving upper limb functionality in chronic stroke. We designed a proof-of-principle, double-blind, semi-randomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 consecutive working days. Efficacy was evaluated by change in upper extremity Fugl-Meyer score. After intervention, there were no adverse events and Fugl-Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in chronic stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.

via Safety, feasibility, and efficacy of transcutaneous vagus nerve stimulation combined with upper-limb robotic rehabilitation after stroke – ScienceDirect

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[WEB SITE] Vagus Nerve Stimulation Enhances Brain Plasticity

Sebastian Kaulitzki/Shutterstock

Vagus nerve illustrated in yellow.
Source: Sebastian Kaulitzki/Shutterstock

Vagus nerve stimulation (VNS) enhances targeted neuroplasticity, helping the brain build stronger neural connections after a stroke, according to pioneering research from the University of Texas at Dallas. Using an animal model, the researchers have demonstrated for the first time that pairing VNS with a physical therapy task accelerates the recovery of motor skills.

The researchers published their findings, “Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery,” in the journal Stroke. A human clinical trial of the same treatment, “Pivotal Study of VNS During Rehab After Stroke (VNS-REHAB),” is currently underway at 18 research sites across the US and in the UK. The goal of the study is to gauge the efficacy of paired vagus nerve stimulation in helping stroke patients recover motor skills more quickly.

What Is Vagus Nerve Stimulation?

Alila Medical Media/Shutterstock

Source: Alila Medical Media/Shutterstock

Vagus nerve stimulation is delivered via a small, surgically implanted device that uses electrical impulses of varying intensities and pulse-widths to activate the vagus nerve. Electrical stimulation of the vagus nerve using VNS is an FDA-approved treatment for drug-resistant epilepsy and treatment-resistant depression. A recent proof-of-concept human study also found that VNS is a viable treatment for inflammatory joint diseases such as rheumatoid arthritis.

The sudden loss of blood flow after a stroke causes neurons in any stroke-affected brain region to die, which cuts off connections to other nerve cells. The loss of motor skills in an arm or leg after a stroke is caused by a loss of connectivity between nerve cells in the limb with corresponding motor regions of the brain.

Using an animal model, the UT Dallas researchers found that brief bursts of VNS strengthen communication pathways by building stronger cell connections in the brain after a stroke. In fact, their results show that coupling VNS with targeted movement therapies dramatically boosts the benefit of rehabilitative training after a stroke. And, in animal studies, these improvements lasted for months after the completion of VNS targeted therapy.

As the authors of this study, led by Eric C. Meyers, explain: “This study provides the first evidence that VNS paired with rehabilitative training after stroke (1) doubles long-lasting recovery on a complex task involving forelimb supination, (2) doubles recovery on a simple motor task that was not paired with VNS, and (3) enhances structural plasticity in motor networks.”

Michael Kilgard, associate director of the Texas Biomedical Device Center and professor of neuroscience in the School of Behavioral and Brain Sciences at UT Dallas, was a senior co-author of this research. Kilgard is the principal investigator at the UTD Cortical Plasticity Laboratory. His teamalso includes Seth Hays, a postdoctoral researcher in the School of Behavioral and Brain Sciences at UT Dallas, who specializes in targeted plasticity therapy to alleviate motor dysfunction.

“Our experiment was designed to ask this new question: After a stroke, do you have to rehabilitate every single action?” Kilgard said in a statement. “If VNS helps you, is it only helping with the exact motion or function you paired with stimulation? What we found was that it also improves similar motor skills as well, and that those results were sustained months beyond the completion of VNS-paired therapy.”

The UT Dallas researchers are optimistic that their latest research on targeted vagus nerve stimulation is a pivotal step toward creating guidelines for standardized usage of VNS during post-stroke therapy in humans. “We have long hypothesized that VNS is making new connections in the brain, but nothing was known for sure,” Hays said in a statement. “This is the first evidence that we are driving changes in the brain in animals after brain injury. It’s a big step forward in understanding how the therapy works — this reorganization that we predicted would underlie the benefits of VNS.”

Another recent study from UT Dallas found that moderate intensity vagus nerve stimulation optimized the neuroplasticity-enhancing and memory-enhancing effects of VNS more effectively than low or high-intensity stimulation. Notably, the researchers pinpointed that the optimal pulse width and current intensity were marked by an “inverted-U” pattern in which too much or too little VNS was less effective than a ‘Goldilocks’ sweet spot of moderate intensity that was just right. These 2017 findings were published in the journal Brain Stimulation.

Paired Vagus Nerve Stimulation Offers New Hope for Stroke Rehabilitation

In 2017, the makers of a vagus nerve stimulation device launched a randomized, double-blind clinical trial of VNS rehab for patients after a cerebrovascular stroke. This study, currently underway, will include up to 120 subjects at 18 clinical locations across the US and in the UK. The estimated conclusion date of preliminary research for this clinical trial is June 30, 2019.

The Ohio State University is one of the institutions participating in the paired VNS clinical trial. Marcie Bockbrader of the Wexner Medical Center at OSU is their principal investigator for the trial.

In a recent press release, Bockbrader said: “This nerve stimulation is like turning on a switch, making the patient’s brain more receptive to therapy. The goal is to see if we can improve motor recovery in people who have what is, in effect, a brain pacemaker implanted in their body. The idea is to combine this brain pacing with normal rehab, and see if patients who’ve been through all of their other usual therapies after a stroke can get even better.”

Below is a YouTube video of Marcie Bockbrader and colleagues in their paired VNS therapy lab along with a patient describing his stroke rehab process:

For this clinical trial, each study participant receives three one-hour sessions of intensive physiotherapy per week for a total of six weeks. The goal is to improve task-specific motor arm function. Half of the group participating in this clinical trial had a vagus nerve stimulation device surgically implanted; the other half will serve as a control group.

During each rehabilitation therapy session, whenever a patient correctly performs a particular motor skill, the therapist pushes a button to trigger an optimal pulse width and current intensity of vagus nerve stimulation. The hypothesis is that if precise and accurate movements are positively reinforced by a brief burst of VNS during a trial-and-error learning process that these actions become “hardwired” into the brain more quickly.

“We are trying to see if this neurostimulator could be used to boost the effective therapy, creating a sort of ‘supercharged therapy.’ We want to determine if patients can recover more quickly through the use of this stimulation,” Bockbrader concluded.

References

Eric C. Meyers, Bleyda R. Solorzano, Justin James, Patrick D. Ganzer, Elaine S. Lai, Robert L. Rennaker, Michael P. Kilgard, Seth A. Hays. “Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke Recovery.” Stroke (First published online: January 25,  2018) DOI: 10.1161/STROKEAHA.117.019202

Kristofer W. Loerwald, Michael S. Borland, Robert L. Rennaker II, Seth A. Hays, Michael P. Kilgard. “The Interaction of Pulse Width and Current Intensity on the Extent of Cortical Plasticity Evoked by Vagus Nerve Stimulation.” Brain Stimulation (First published online: November 15, 2017) DOI: 10.1016/j.brs.2017.11.007

via Vagus Nerve Stimulation Enhances Brain Plasticity | Psychology Today

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[Abstract] Vagus nerve stimulation intensity influences motor cortex plasticity

Highlights

Recovery after neurological injury is thought to be dependent on plasticity.

Moderate intensity VNS paired with motor training enhances motor cortex plasticity.

Low and high intensity VNS paired with motor training fail to enhance plasticity.

The intensity of stimulation is a critical factor in VNS-dependent plasticity.

Optimizing stimulation paradigms may enhance VNS efficacy in clinical populations.

Abstract

Background

Vagus nerve stimulation (VNS) paired with forelimb motor training enhances reorganization of movement representations in the motor cortex. Previous studies have shown an inverted-U relationship between VNS intensity and plasticity in other brain areas, such that moderate intensity VNS yields greater cortical plasticity than low or high intensity VNS. However, the relationship between VNS intensity and plasticity in the motor cortex is unknown.

Objective

In this study we sought to test the hypothesis that VNS intensity exhibits an inverted-U relationship with the degree of motor cortex plasticity in rats.

Methods

Rats were taught to perform a lever pressing task emphasizing use of the proximal forelimb musculature. Once proficient, rats underwent five additional days of behavioral training in which low intensity VNS (0.4 mA), moderate intensity VNS (0.8 mA), high intensity VNS (1.6 mA), or sham stimulation was paired with forelimb movement. 24 h after the completion of behavioral training, intracortical microstimulation (ICMS) was used to document movement representations in the motor cortex.

Results

VNS delivered at 0.8 mA caused a significant increase in motor cortex proximal forelimb representation compared to training alone. VNS delivered at 0.4 mA and 1.6 mA failed to cause a significant expansion of proximal forelimb representation.

Conclusion

Moderate intensity 0.8 mA VNS optimally enhances motor cortex plasticity while low intensity 0.4 mA and high intensity 1.6 mA VNS fail to enhance plasticity. Plasticity in the motor cortex exhibits an inverted-U function of VNS intensity similar to previous findings in auditory cortex.

via Vagus nerve stimulation intensity influences motor cortex plasticity – Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation

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