Posts Tagged Vagus Nerve Stimulation

[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.

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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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[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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[Abstract + References] Improving Stroke Rehabilitation with Vagus Nerve Stimulation

Abstract

Stroke is a leading cause of neurological damage, with an estimated 795,000 cases reported in the United States each year. A large percentage of patients who suffer a stroke exhibit long-term impairments in motor function. Poststroke rehabilitation in part aims to promote adaptive changes in neural circuits to support recovery of function, but insufficient or maladaptive plasticity often limits benefits. Adjunctive strategies that support plasticity in conjunction with rehabilitation represent a potential means to improve recovery after stroke. Vagus nerve stimulation (VNS) has emerged as one such targeted plasticity strategy, providing phasic activation of neuromodulatory nuclei associated with plasticity. Repeatedly pairing brief bursts of VNS with motor training drives robust, specific plasticity in neural circuits. A number of studies in animal models of stroke and neurological injury demonstrate that VNS paired with rehabilitative training improves recovery of motor function. Moreover, emerging evidence from clinical trials indicates that VNS delivered during rehabilitation promotes functional recovery in stroke patients. Here, we provide a discussion of the existing literature of VNS-based targeted plasticity therapies in the context of stroke and outline challenges for clinical implementation.

References

  1. 1.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135:e146–603.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Dobkin BH. Strategies for stroke rehabilitation. Lancet Neurol. 2004;3:528–36.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Dobkin BH. Rehabilitation after stroke. N Engl J Med. 2005;352:1677–84.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lai S, Studenski S, Duncan PW, Perera S. Persisting consequences of stroke measured by the stroke impact scale. Stroke. 2002;33:1840–4.CrossRefPubMedGoogle Scholar
  5. 5.
    Calautti C, Baron J. Functional neuroimaging studies of motor recovery after stroke in adults a review. Stroke. 2003;34:1553–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Nudo R, Friel K. Cortical plasticity after stroke: implications for rehabilitation. Rev Neurol. 1999;155:713.PubMedGoogle Scholar
  7. 7.
    Zhang J, Meng L, Qin W, Liu N, Shi FD, Yu C. Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke. Stroke. 2014;45:788–93.CrossRefPubMedGoogle Scholar
  8. 8.
    Liepert J, Miltner W, Bauder H, Sommer M, Dettmers C, Taub E, Weiller C. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neurosci Lett. 1998;250:5–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Hallett M. Plasticity of the human motor cortex and recovery from stroke. Brain Res Rev. 2001;36:169–74.CrossRefPubMedGoogle Scholar
  10. 10.
    Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF. Rates and predictors of seizure freedom with vagus nerve stimulation for intractable epilepsy. Neurosurgery. 2016;79:345–53.CrossRefPubMedGoogle Scholar
  11. 11.
    Heck C, Helmers SL, DeGiorgio CM. Vagus nerve stimulation therapy, epilepsy, and device parameters scientific basis and recommendations for use. Neurology. 2002;59:S31–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Hays SA. Enhancing rehabilitative therapies with vagus nerve stimulation. Neurotherapeutics. 2016;13(2):382–94.CrossRefPubMedGoogle Scholar
  13. 13.
    Hulsey DR, Riley JR, Loerwald KW, Rennaker RL, Kilgard MP, Hays SA. Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation. Exp Neurol. 2016;Google Scholar
  14. 14.
    Hulsey DR, Hays SA, Khodaparast N, Ruiz A, Das P, Rennaker RL, Kilgard MP. Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation. Brain Stimul. 2016;9(2):174–81.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nichols J, Nichols A, Smirnakis S, Engineer N, Kilgard M, Atzori M. Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors. Neuroscience. 2011;189:207–14.CrossRefPubMedGoogle Scholar
  16. 16.
    Seol GH, Ziburkus J, Huang SY, Song L, Kim IT, Takamiya K, Huganir RL, Lee HK, Kirkwood A. Neuromodulators control the polarity of spike-timing-dependent synaptic plasticity. Neuron. 2007;55:919–29.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    He K, Huertas M, Hong S, Tie X, Hell J, Shouval H, Kirkwood A. Distinct eligibility traces for LTP and LTD in cortical synapses. Neuron. 2015;88:528–38.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Flood JF, Smith GE, Morley JE. Modulation of memory processing by cholecystokinin: dependence on the vagus nerve. Science. 1987;236:832–4.CrossRefPubMedGoogle Scholar
  19. 19.
    Flood JF, Morley JE. Effects of bombesin and gastrin-releasing peptide on memory processing. Brain Res. 1988;460:314–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Williams C, Jensen RA. Effects of vagotomy on Leu-enkephalin-induced changes in memory storage processes. Physiol Behav. 1993;54:659–63.CrossRefPubMedGoogle Scholar
  21. 21.
    Jensen RA. Modulation of memory storage processes by peripherally acting pharmacological agents. Proc West Pharmacol Soc. 1996;39:85–9.PubMedGoogle Scholar
  22. 22.
    Talley CP, Clayborn H, Jewel E, McCarty R, Gold PE. Vagotomy attenuates effects of L-glucose but not of D-glucose on spontaneous alternation performance. Physiol Behav. 2002;77:243–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Nogueira PJ, Tomaz C, Williams CL. Contribution of the vagus nerve in mediating the memory-facilitating effects of substance P. Behav Brain Res. 1994;62:165–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Clark K, Krahl S, Smith D, Jensen R. Post-training unilateral vagal stimulation enhances retention performance in the rat. Neurobiol Learn Mem. 1995;63:213–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Clark KB, Naritoku DK, Smith DC, Browning RA, Jensen RA. Enhanced recognition memory following vagus nerve stimulation in human subjects. Nat Neurosci. 1999;2:94–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake JA, Sudanagunta SP, Borland MS, Kilgard MP. Reversing pathological neural activity using targeted plasticity. Nature. 2011;470:101–4.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Shetake JA, Engineer ND, Vrana WA, Wolf JT, Kilgard MP. Pairing tone trains with vagus nerve stimulation induces temporal plasticity in auditory cortex. Exp Neurol. 2011;233:342–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Engineer CT, Engineer ND, Riley JR, Seale JD, Kilgard MP. Pairing speech sounds with vagus nerve stimulation drives stimulus-specific cortical plasticity. Brain Stimul. 2015;8(3):637–44.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Borland MS, Vrana WA, Moreno NA, Fogarty EA, Buell EP, Sharma P, Engineer CT, Kilgard MP. Cortical map plasticity as a function of vagus nerve stimulation intensity. Brain Stimul. 2016;9:117–23.CrossRefPubMedGoogle Scholar
  30. 30.
    Porter BA, Khodaparast N, Fayyaz T, Cheung RJ, Ahmed SS, Vrana WA, Rennaker RL II, Kilgard MP. Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. Cereb Cortex. 2011;22:2365–74.CrossRefPubMedGoogle Scholar
  31. 31.
    Khodaparast N, Hays SA, Sloan AM, Fayyaz T, Hulsey DR, Rennaker RL II, Kilgard MP. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabil Neural Repair. 2014;28:698–706.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Hays SA, Khodaparast N, Sloan AM, Fayyaz T, Hulsey DR, Ruiz AD, Pantoja M, Kilgard MP, Rennaker RL II. The bradykinesia assessment task: an automated method to measure forelimb speed in rodents. J Neurosci Methods. 2013;214:52–61.CrossRefPubMedGoogle Scholar
  33. 33.
    Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL II, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiol Dis. 2013;60:80–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Canning CG, Ada L, Adams R, O’Dwyer NJ. Loss of strength contributes more to physical disability after stroke than loss of dexterity. Clin Rehabil. 2004;18:300–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Harris JE, Eng JJ. Paretic upper-limb strength best explains arm activity in people with stroke. Phys Ther. 2007;87:88–97.CrossRefPubMedGoogle Scholar
  36. 36.
    Hays SA, Khodaparast N, Ruiz A, Sloan AM, Hulsey DR, Rennaker RL, Kilgard MP. The timing and amount of vagus nerve stimulation during rehabilitative training affect post-stroke recovery of forelimb strength. Neuroreport. 2014;25(9):676–82.CrossRefPubMedGoogle Scholar
  37. 37.
    Kelly-Hayes M, Beiser A, Kase CS, Scaramucci A, D’Agostino RB, Wolf PA. The influence of gender and age on disability following ischemic stroke: the Framingham study. J Stroke Cerebrovasc Dis. 2003;12:119–26.CrossRefPubMedGoogle Scholar
  38. 38.
    Freitas C, Perez J, Knobel M, Tormos JM, Oberman L, Eldaief M, Bashir S, Vernet M, Peña-Gómez C, Pascual-Leone A. Changes in cortical plasticity across the lifespan. Front Aging Neurosci. 2011;3Google Scholar
  39. 39.
    Pascual-Leone A, Freitas C, Oberman L, Horvath JC, Halko M, Eldaief M, Bashir S, Vernet M, Shafi M, Westover B. Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI. Brain Topogr. 2011;24:302–15.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hays SA, Ruiz A, Bethea T, Khodaparast N, Carmel JB, Rennaker RL, Kilgard MP. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. Neurobiol Aging. 2016;43:111–8.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bagg S, Pombo AP, Hopman W. Effect of age on functional outcomes after stroke rehabilitation. Stroke. 2002;33:179–85.CrossRefPubMedGoogle Scholar
  42. 42.
    Kwakkel G, Kollen BJ, van der Grond J, Prevo AJH. Probability of regaining dexterity in the flaccid upper limb impact of severity of paresis and time since onset in acute stroke. Stroke. 2003;34:2181–6.CrossRefPubMedGoogle Scholar
  43. 43.
    Biernaskie J, Chernenko G, Corbett D. Efficacy of rehabilitative experience declines with time after focal ischemic brain injury. J Neurosci. 2004;24:1245–54.CrossRefPubMedGoogle Scholar
  44. 44.
    Teasell R, Bitensky J, Salter K, Bayona NA. The role of timing and intensity of rehabilitation therapies. Top Stroke Rehabil. 2005;12:46.CrossRefPubMedGoogle Scholar
  45. 45.
    Salter BK, Hartley BM, Foley BN. Impact of early vs delayed admission to rehabilitation on functional outcomes in persons with stroke. J Rehabil Med. 38, 2006;Google Scholar
  46. 46.
    Khodaparast N, Kilgard MP, Casavant R, Ruiz A, Qureshi I, Ganzer PD, Rennaker RL 2nd, Hays SA. Vagus nerve stimulation during rehabilitative training improves forelimb recovery after chronic ischemic stroke in rats. Neurorehabil Neural Repair. 2016;30(7):676–84.CrossRefPubMedGoogle Scholar
  47. 47.
    Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344:1450–60.CrossRefPubMedGoogle Scholar
  48. 48.
    Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5:53–63.CrossRefPubMedGoogle Scholar
  49. 49.
    Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson LM, Truelsen T. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990–2010: findings from the global burden of disease study 2010. Lancet Glob Health. 2013;1:e259–81.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Auriat AM, Wowk S, Colbourne F. Rehabilitation after intracerebral hemorrhage in rats improves recovery with enhanced dendritic complexity but no effect on cell proliferation. Behav Brain Res. 2010;214:42–7.CrossRefPubMedGoogle Scholar
  51. 51.
    M. Santos, A. Pagnussat, R. Mestriner, C. Netto. Motor skill training promotes sensorimotor recovery and increases microtubule-associated protein-2 (MAP-2) immunoreactivity in the motor cortex after intracerebral hemorrhage in the rat. ISRN Neurol 2013. (2013).Google Scholar
  52. 52.
    Liang H, Yin Y, Lin T, Guan D, Ma B, Li C, Wang Y, Zhang X. Transplantation of bone marrow stromal cells enhances nerve regeneration of the corticospinal tract and improves recovery of neurological functions in a collagenase-induced rat model of intracerebral hemorrhage. Mol Cells. 2013;36:17–24.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Hays SA, Khodaparast N, Hulsey DR, Ruiz A, Sloan AM, Rennaker RL II, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke. 2014;45(10):3097–30100.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Pruitt D, Schmid A, Kim L, Abe C, Trieu J, Choua C, Hays S, Kilgard M, Rennaker RL II. Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury. J Neurotrauma. 2016;33(9):871–9.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, Hilmi O, McLean J, Forbes K, Kilgard MP, Rennaker RL, Cramer SC, Walters M, Engineer N. Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke. 2016;47:143–50.CrossRefPubMedGoogle Scholar
  56. 56.
    Clinical Trials Identifier: NCT01669161, Paired vagus nerve stimulation (VNS) with rehabilitation for upper limb function improvement after stroke. ClinicalTrials. gov. Bethesda: National Library of Medicine (US). https://clinicaltrials.gov/ct2/show/NCT01669161 (2014).
  57. 57.
    Dawson J, McGrane F. Vagus nerve stimulation and upper limb rehabilitation. Curr Phys Med Rehabil Rep. 2016;4:186–9.CrossRefGoogle Scholar
  58. 58.
    Clinical Trials Identifier: NCT02243020, .VNS during rehabilitation for improved upper limb motor function after stroke. ClinicalTrials. gov. Bethesda: National Library of Medicine (US). https://clinicaltrials.gov/ct2/show/study/NCT02243020 (2014).
  59. 59.
    Krahl SE, Senanayake SS, Handforth A. Destruction of peripheral C-fibers does not Alter subsequent vagus nerve stimulation-induced seizure suppression in rats. Epilepsia. 2001;42:586–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Ruffoli R, Giorgi FS, Pizzanelli C, Murri L, Paparelli A, Fornai F. The chemical neuroanatomy of vagus nerve stimulation. J Chem Neuroanat. 2011;42:288–96.CrossRefPubMedGoogle Scholar
  61. 61.
    Evans M, Verma-Ahuja S, Naritoku D, Espinosa J. Intraoperative human vagus nerve compound action potentials. Acta Neurol Scand. 2004;110:232–8.CrossRefPubMedGoogle Scholar
  62. 62.
    T. Verlinden, K. Rijkers, G. Hoogland, A. Herrler. Morphology of the human cervical vagus nerve: implications for vagus nerve stimulation treatment. Acta Neurol Scand. (2015).Google Scholar
  63. 63.
    Hammer N, Glätzner J, Feja C, Kühne C, Meixensberger J, Planitzer U, Schleifenbaum S, Tillmann BN, Winkler D. Human vagus nerve branching in the cervical region. PLoS One. 2015;10:e0118006.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    U. Planitzer, N. Hammer, I. Bechmann, J. Glätzner, S. Löffler, R. Möbius, B. N. Tillmann, D. Weise, D. Winkler. Positional relations of the cervical vagus nerve revisited. In: Neuromodulation: technology at the neural interface. (2017).Google Scholar
  65. 65.
    Roosevelt RW, Smith DC, Clough RW, Jensen RA, Browning RA. Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat. Brain Res. 2006;1119:124–32.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Castoro MA, Yoo PB, Hincapie JG, Hamann JJ, Ruble SB, Wolf PD, Grill WM. Excitation properties of the right cervical vagus nerve in adult dogs. Exp Neurol. 2011;227:62–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Mollet L, Raedt R, Delbeke J, El Tahry R, Grimonprez A, Dauwe I, De Herdt V, Meurs A, Wadman W, Boon P. Electrophysiological responses from vagus nerve stimulation in rats. Int J Neural Syst. 2013;23:1350027.CrossRefPubMedGoogle Scholar
  68. 68.
    Clark K, Smith D, Hassert D, Browning R, Naritoku D, Jensen R. Posttraining electrical stimulation of vagal afferents with concomitant vagal efferent inactivation enhances memory storage processes in the rat. Neurobiol Learn Mem. 1998;70:364–73.CrossRefPubMedGoogle Scholar
  69. 69.
    Follesa P, Biggio F, Gorini G, Caria S, Talani G, Dazzi L, Puligheddu M, Marrosu F, Biggio G. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res. 2007;1179:28–34.CrossRefPubMedGoogle Scholar
  70. 70.
    Ploughman M, Windle V, MacLellan CL, White N, Doré JJ, Corbett D. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke. 2009;40:1490–5.CrossRefPubMedGoogle Scholar
  71. 71.
    Schäbitz W, Berger C, Kollmar R, Seitz M, Tanay E, Kiessling M, Schwab S, Sommer C. Effect of brain-derived neurotrophic factor treatment and forced arm use on functional motor recovery after small cortical ischemia. Stroke. 2004;35:992–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Dan Y, Poo M. Spike timing-dependent plasticity of neural circuits. Neuron. 2004;44:23–30.CrossRefPubMedGoogle Scholar
  73. 73.
    Alvarez-Dieppa AC, Griffin K, Cavalier S, McIntyre CK. Vagus nerve stimulation enhances extinction of conditioned fear in rats and modulates arc protein, CaMKII, and GluN2B-containing NMDA receptors in the basolateral amygdala. Neural Plast. 2016;2016Google Scholar
  74. 74.
    Xu T, Yu X, Perlik AJ, Tobin WF, Zweig JA, Tennant K, Jones T, Zuo Y. Rapid formation and selective stabilization of synapses for enduring motor memories. Nature. 2009;462:915–9.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Ay I, Lu J, Ay H, Gregory Sorensen A. Vagus nerve stimulation reduces infarct size in rat focal cerebral ischemia. Neurosci Lett. 2009;459:147–51.CrossRefPubMedGoogle Scholar
  76. 76.
    Ay I, Ay H. Ablation of the sphenopalatine ganglion does not attenuate the infarct reducing effect of vagus nerve stimulation. Auton Neurosci. 2013;174:31–5.CrossRefPubMedGoogle Scholar
  77. 77.
    Ay I, Nasser R, Simon B, Ay H. Transcutaneous cervical vagus nerve stimulation ameliorates acute ischemic injury in rats. Brain Stimul. 2015;9(2):166–73.CrossRefPubMedPubMedCentralGoogle Scholar

via Improving Stroke Rehabilitation with Vagus Nerve Stimulation | SpringerLink

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[ARTICLE] Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke – Full Text

Abstract

Background and Purpose—Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke.

Methods—Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl–Meyer Assessment-Upper Extremity).

Results—Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl–Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, −0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl–Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6).

Conclusions—This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed.

Introduction

Arm weakness is common after stroke, and its treatment is recognized as an area of considerable need.1 Approximately 85% of patients with stroke present with arm weakness,2 and 60% of stroke survivors with nonfunctional arms at 1 week do not recover function by 6 months.3Current treatment for arm weakness typically comprises intensive, task-specific, and repetitive rehabilitative interventions or occasionally methods such as constraint-induced movement therapy and electric neurostimulation.4 A recent meta-analysis and large-scale trials show the effects of current treatments for arm weakness to be modest.5,6 Novel and more effective treatments are needed. Improvement in arm function should improve quality of life for stroke survivors, reduce comorbidities associated with loss of independence, and reduce cost to the healthcare system.7

Intensive training has been shown to facilitate a range of neuroplastic brain events.8 It is possible that augmentation of neuroplasticity to promote reorganization of neural networks is required to more fully recover motor function.9 However, no practical and effective method exists to achieve this and even if such changes occur, it is unclear whether they are clinically meaningful or long term. This study is a preliminary investigation of an intervention designed to promote specific neuroplasticity; vagus nerve stimulation (VNS) paired with movement to drive task-specific plasticity in the motor cortex.1012 VNS activates neurons in the basal forebrain and locus coeruleus and results in release of acetylcholine and norepinephrine, respectively, which are known to facilitate reorganization of cortical networks.13 We recently demonstrated in a rat model of ischemic stroke that pairing forelimb rehabilitation with VNS significantly increases recovery of forelimb speed and strength when compared with rehabilitation alone.14,15 Our subsequent studies demonstrated that VNS paired with rehabilitative training also improves recovery in a rat model of intracerebral hemorrhage,16 and that precise timing of VNS with specific motor movements yields optimal recovery.17

We hypothesize that VNS paired with upper-limb rehabilitation therapy will result in greater recovery of arm function than rehabilitation alone in adults with chronic ischemic stroke. We performed the first-in-human evaluation of VNS paired with upper-limb rehabilitation after ischemic stroke. The main objective of the study was to evaluate the safety and feasibility of paired VNS therapy after stroke and to provide clinical data for sample size calculations for larger studies. […]

 

Continue —> Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke | Stroke

Figure 1. Schematic of vagus nerve stimulation device use in a typical therapy session.

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[ARTICLE] Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation Improves Upper Limb Function after Stroke – Full Text

Abstract

The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, 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 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 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.

1. Introduction

Upper limb impairment is a common consequence of stroke with a deep impact on patient’s quality of life. Since the efficacy of standard rehabilitative therapy is limited, alternative strategies are needed. Robot-assisted rehabilitation can be useful in stroke patients because it allows an intensive as well as task-specific training characterized by high repetition of movements in a strongly motivating environment [13]. Several studies have explored the possibility to potentiate the effect of robotic therapy by the association with noninvasive human brain stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), that can induce neuroplasticity via long-term potentiation-/depression- (LTP-/LTD-) like phenomena [4]. Although intriguing, the evidence in support of this strategy remains low [56]. Indeed, the literature analysis of the published data seems to demonstrate that the association of rTMS with robotic training has the same clinical gain derived from robotic therapy alone. Moreover, rTMS is contraindicated in patients who suffered from haemorrhagic stroke for the risk of inducing seizures [7]. For these reasons, there is great interest in the development of alternative techniques of neuromodulation that can foster the effect of robotic therapy.

Vagus nerve stimulation (VNS) is approved as adjunctive treatment for refractory epilepsy and depression but is currently under investigation for a wide range of neurological diseases [8]. In particular, recent studies have demonstrated that VNS paired with rehabilitation significantly improves forelimb strength and movement speed in rat models of ischemic [9] and haemorrhagic stroke [10]. VNS is believed to enhance the benefits of rehabilitation by promoting neuroplasticity [11]. Preliminary data [12] have showed that such approach is also feasible in patients; however, the diffusion of this technique is limited by its invasiveness. Indeed, VNS requires the surgical implantation of a stimulator of the cervical branch of the vagus nerve. Recently, it has been proposed a noninvasive technique that consists of transcutaneous stimulation of the vagus nerve (tVNS) in external auditory channel at the inner side of the tragus. Both neuroimaging [13] and neurophysiological [14] studies have demonstrated that the effect of tVNS on brain activity is quite similar to the effect induced by traditional, invasive VNS.

The aim of the present study was to explore whether tVNS can enhance the benefit induced by robotic rehabilitation on motor function of the upper limb in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. […]

Continue —> Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation Improves Upper Limb Function after Stroke

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[WEB SITE] Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy – NEUROSURGERY Report

Abstract

BACKGROUND: Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response.

OBJECTIVE: To elucidate rates and predictors of seizure freedom with VNS.

METHODS: We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies.

RESULTS: Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom.

CONCLUSION: Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients.

Source: Open Access: Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy | NEUROSURGERY Report

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[ARTICLE] Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy – Full Text

Abstract

BACKGROUND: Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response.

OBJECTIVE: To elucidate rates and predictors of seizure freedom with VNS.

METHODS: We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies.

RESULTS: Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom.

CONCLUSION: Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients.

 

Approximately 1% of the population has epilepsy, and seizures are refractory to antiepileptic drugs (AEDs) in approximately 30% of these individuals.1 Many patients with drug-resistant temporal or extratemporal lobe epilepsy can become seizure-free with surgical resection or ablation, but other patients with epilepsy are not candidates for resection given the presence of primary generalized seizures, nonlocalizable or multifocal seizure onset, or seizure onset from an eloquent brain region.2-5 Treatments based on neuromodulation, such as vagus nerve stimulation (VNS), have, therefore, become an increasingly important part of multimodal epilepsy treatment. VNS therapy was approved by the US Food and Drug Administration in 1997 as an adjunctive therapy for reducing seizures in patients with medically refractory epilepsy, and more than 80 000 patients have received treatment with VNS.6-8 The efficacy of VNS therapy has been evaluated by randomized controlled trials,9,10 retrospective case series,11,12 meta-analysis,13 and registry-based studies.14 These studies show that about 50% to 60% of patients achieve ≥50% reduction in seizure frequency after 2 years of treatment, and response rates increase over time, likely related to neuromodulatory effects with ongoing stimulation.13 Complete seizure freedom, however, is less common with VNS therapy and other neuromodulation treatment modalities.

Given that a minority of patients achieve seizure freedom with VNS, rates and predictors of seizure freedom have not been well studied and remain poorly understood. The vast majority of studies that evaluate VNS therapy focus on rate of response over time (defined as ≥50% reduction in seizures) and predictors of response; there has never been a large-scale evaluation of seizure freedom as a primary end point in patients treated with VNS. However, seizure freedom is the single best predictor of quality of life in patients with epilepsy,15,16 and therefore a better understanding of seizure freedom rates and predictors in patients treated with VNS therapy is critically needed. Importantly, this information may lead to improved patient selection and counseling in the treatment of drug-resistant epilepsy.

Here, we provide the first large-scale study of VNS therapy with a primary goal of defining seizure freedom rates and predictors, and comparing predictors of seizure freedom with those of overall response to treatment. Our study includes univariate and multivariate analyses of registry data including 5554 patients treated with VNS, and also includes a systematic review of the literature including 2869 patients across 78 studies, to help confirm registry-based results.

Continue —> Rates and Predictors of Seizure Freedom With Vagus Nerve Sti… : Neurosurgery

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[ARTICLE] Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury

ABSTRACT

Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly two million people every year. The effects of TBI, including weakness and loss of coordination, can be debilitating and last years after the initial injury. Recovery of motor function is often incomplete. We have developed a method using electrical stimulation of the vagus nerve paired with forelimb use by which we have demonstrated enhanced recovery from ischemic and hemorrhagic stroke. Here we have tested the hypothesis that vagus nerve stimulation (VNS) paired with physical rehabilitation could enhance functional recovery after TBI. We trained rats to pull on a handle to receive a food reward. Following training, they received a controlled-cortical impact (CCI) in the forelimb area of motor cortex opposite the trained forelimb, and were then randomized into two treatment groups. One group of animals received vagus nerve stimulation (VNS) paired with rehabilitative therapy, while another group received rehabilitative therapy without VNS. Following CCI, volitional forelimb strength and task success rate in all animals were significantly reduced. VNS paired with rehabilitative therapy over a period of five weeks significantly increased recovery of both forelimb strength and hit rate on the isometric pull task compared to rehabilitative training without VNS. No significant improvement was observed in the Rehab group. Our findings indicate that VNS paired with rehabilitative therapy enhances functional motor recovery after TBI.

via Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury | Abstract.

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