Vagus Nerve Stimulation During Rehabilitative Training Improves Functional Recovery After Intracerebral Hemorrhage

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

doi:10.1161/strokeaha.114.006654

Cited by 119 publications

(113 citation statements)

References 14 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%

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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%

“…Our group evaluated whether VNS paired with rehabilitative training could improve recovery of forelimb function in a rat model of ICH [75]. Rats were trained to proficiency on a skilled forelimb task and then received a severe hemorrhagic lesion in the midbrain to impair use of the trained forelimb.…”

Section: Preclinical Studies For Intracerebral Hemorrhagementioning

confidence: 99%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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“…Vagus nerve stimulation (VNS) is a minimally invasive neuroprosthetic approach that might be used to provide tight temporal and circuit-specific modulation of brain areas and synapses engaged in an ongoing task. A series of recent studies from Michael Kilgard's group at The University of Texas at Dallas have shown that pairing VNS with discrete sensory or motor stimuli (e.g., a tone or a lever pull) is highly effective in promoting cortical plasticity to treat tinnitus 7 , or to overcome motor deficits following stroke [8][9][10] . In addition, non-contingent VNS that occurs within a short time-window after learning similarly promotes cortical plasticity and enhances memory consolidation in rats and in humans [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

“…These effects have already been used clinically to reverse pathological plasticity in the auditory cortex to treat tinnitus 50 . Similarly, repeated pairing of VNS with a motor behavior has been shown to reorganize motor cortex 8 and this targeted plasticity is highly effective in the recovery of function in different animal models of stroke 9,10 .…”

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confidence: 99%

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Childs

Alvarez-Dieppa

McIntyre

et al. 2015

JoVE

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Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory. Video LinkThe video component of this article can be found at

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“…[5][6][7][8] Recently, an implementation that uses short bursts of VNS paired with rehabilitative therapy has been demonstrated to enhance functional recovery in animal models of stroke. [9][10][11][12] In both ischemic and hemorrhagic models of stroke, pairing VNS with rehabilitation improved multiple measures of forelimb performance. 9,12 Given the effectiveness of pairing VNS with physical rehabilitation to enhance functional recovery in multiple models of brain injury and neurological disorders, we hypothesized that VNS would also be an effective tool to enhance functional recovery following TBI.…”

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confidence: 99%

Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury

Pruitt

Schmid

Kim

et al. 2016

Journal of Neurotrauma

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119

127

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Traumatic Brain Injury (TBI) is one of the largest health problems in the United States, and affects nearly 2 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 VNS paired with rehabilitative therapy, whereas 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 5 weeks significantly increased recovery of both forelimb strength and success rate on the isometric pull task compared with 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.

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Vagus Nerve Stimulation During Rehabilitative Training Improves Functional Recovery After Intracerebral Hemorrhage

Cited by 119 publications

References 14 publications

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Vagus Nerve Stimulation Delivered with Motor Training Enhances Recovery of Function after Traumatic Brain Injury

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