Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke

Khodaparast, Navid; Hays, Seth A.; Sloan, Andrew M.; Hulsey, Daniel R.; Ruiz, Andrea; Pantoja, Maritza; Rennaker, Robert L.; Kilgard, Michael P.

doi:10.1016/j.nbd.2013.08.002

Cited by 126 publications

(174 citation statements)

References 93 publications

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“…VNS paired with rehabilitative training significantly improved recovery of volitional forelimb strength compared with rehabilitative training without VNS after TBI. Consistent with previous studies, VNS did not reduce lesion size, suggesting that VNS does not improve motor recovery through gross neuroprotection [59,60,75]. These findings extend the efficacy of VNS paired with rehabilitative training to a model of TBI.…”

Section: Preclinical Studies For Traumatic Brain Injurysupporting

confidence: 89%

“…VNS paired with rehabilitative training fully restored forelimb performance by the second week of treatment and significantly improved recovery compared to rehabilitative training without VNS. A second study by the same group extended these findings to recovery of forelimb strength after stroke [60]. VNS paired with rehabilitative training resulted in significantly greater recovery of volitional forelimb strength over the course of therapy compared with rehabilitative training without VNS.…”

Section: Preclinical and Clinical Studies For Ischemic Strokementioning

confidence: 79%

“…VNS paired with rehabilitative training resulted in significantly improved forelimb function compared to rehabilitative training without VNS. However, VNS therapy failed to restore fully forelimb function to prelesion levels, unlike the complete recovery observed in models of ischemic stroke [59][60][61]. To determine whether recovery was limited by an insufficient amount of VNS, a cohort of rats received VNS delivered on every attempted trial rather than only successful trials, resulting in~40 % more paired stimulations during therapy.…”

Section: Preclinical Studies For Intracerebral Hemorrhagementioning

confidence: 99%

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Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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Section: Preclinical Studies For Traumatic Brain Injurysupporting

confidence: 89%

Section: Preclinical and Clinical Studies For Ischemic Strokementioning

confidence: 79%

Section: Preclinical Studies For Intracerebral Hemorrhagementioning

confidence: 99%

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Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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“…Behavioral deficits in animal models of chronic ischemic stroke, intracerebral hemorrhage, and traumatic brain injury improve significantly more when VNS is paired with rehabilitative training compared to rehabilitation alone Khodaparast, 2013Pruitt, 2016). Importantly, VNS provides no benefit when it is delivered two hours after the end of daily rehabilitation .…”

Section: Discussionmentioning

confidence: 99%

“…VNS is used to reduce seizure frequency in some patients with epilepsy (Howland, 2014) with a 30 seconds on, 5 minutes off stimulation paradigm. Animal research indicates that brief, 0.5 second bursts of 0.8 mA VNS triggers release of norepinephrine and acetylcholine in the cerebral cortex, which can restore synaptic connectivity after brain injury and improve function if delivered during rehabilitative training , 2014, Hulsey, 2016, 2017, Khodaparast, 2013Nichols, 2011;Porter, 2012;Pruitt, 2016). It is not yet known, whether brief bursts of VNS paired with tactile discrimination training can improve the recovery of sensory function after stroke.…”

Section: Introductionmentioning

confidence: 99%

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient

Kilgard

Rennaker

Alexander

et al. 2018

NRE

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BACKGROUND:Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitation can enhance neural plasticity in the primary sensory and motor cortices, improve forelimb function after stroke in animal models and improve motor function in patients with arm weakness after stroke. OBJECTIVE:To gain "first-in-man" experience of VNS paired with tactile training in a patient with severe sensory impairment after stroke. METHODS:During the long-term follow-up phase of a clinical trial of VNS paired with motor rehabilitation, a 71-year-old man who had made good motor recovery had ongoing severe sensory loss in his left hand and arm. He received VNS paired with tactile therapy in an attempt to improve his sensory function. During twenty 2-hour sessions, each passive and active tactile event was paired with a 0.5 second burst of 0.8 mA VNS. Sensory function was measured before, halfway through, and after this therapy. RESULTS:The patient did not report any side effects during or following VNS+Tactile therapy. Quantitative measures revealed lasting and clinically meaningful improvements in tactile threshold, proprioception, and stereognosis. After VNS+Tactile therapy, the patient was able to detect tactile stimulation to his affected hand that was eight times less intense, identify the joint position of his fingers in the affected hand three times more often, and identify everyday objects using his affected hand seven times more often, compared to baseline. CONCLUSIONS:Sensory function significantly improved in this man following VNS paired with tactile stimulation. This approach merits further study in controlled clinical trials.

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Restoration of Somatosensory Function by Pairing Vagus Nerve Stimulation with Tactile Rehabilitation

Darrow

Mian

Torres

et al. 2020

Annals of Neurology

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ObjectiveSensory dysfunction is a common consequence of many forms of neurological injury, including stroke and nerve damage. Rehabilitative paradigms that incorporate sensory retraining can provide modest benefits, but the majority of patients are left with lasting sensory loss. We have developed a novel strategy that uses closed‐loop vagus nerve stimulation (VNS) paired with tactile rehabilitation to enhance synaptic plasticity and facilitate recovery of sensory function.MethodsA clinical case report provides initial evidence that a similar implementation of closed‐loop VNS paired with a tactile rehabilitation regimen could improve recovery of somatosensory function. Here, we sought to build on these promising initial clinical data and rigorously evaluate the ability of VNS paired with tactile rehabilitation to improve recovery in an animal model of chronic sensory loss. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection (https://osf.io/xsnj5/).ResultsVNS paired with tactile rehabilitation resulted in a significant and nearly complete recovery of mechanosensory withdrawal thresholds. Equivalent tactile rehabilitation without VNS failed to improve sensory function. This VNS‐dependent restoration of sensory thresholds was maintained for several months after the cessation of stimulation, illustrating long‐term benefits. Moreover, VNS paired with tactile rehabilitation resulted in significant generalized improvements in other measures of sensorimotor forepaw function.InterpretationGiven the safety and tolerability of VNS therapy, these findings suggest that incorporating VNS paired with sensory retraining into rehabilitative regimens may represent a fundamentally new method to increase recovery of sensory function after neurological injury. ANN NEUROL 2020;87:194–205

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Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke

Cited by 126 publications

References 93 publications

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient

Restoration of Somatosensory Function by Pairing Vagus Nerve Stimulation with Tactile Rehabilitation

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