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

Abstract

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

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

“…VNS also improved rehabilitation in cervical spine injury rats ( Darrow et al, 2020b ). There was benefit to somatosensory rehabilitation using similar parameters to those used by motor recovery experiments ( Darrow et al, 2020a ).…”

“…Plasticity is a consistent and strong field of VNS research that may shed light on many fundamental principles of neuroscience as a whole. There are several other studies examined in this section and Table 4 but not discussed in detail ( Clark et al, 1995 , 1999 ; Bajbouj et al, 2007 ; Biggio et al, 2009 ; Vanneste et al, 2017 ; Buell et al, 2019 ; Hulsey et al, 2019 ; Meyers et al, 2019 ; Sanders et al, 2019 ; Darrow et al, 2020a , b ).…”

Common Cholinergic, Noradrenergic, and Serotonergic Drugs Do Not Block VNS-Mediated Plasticity

“…Vagus nerve stimulation paired with rehabilitation enhances recovery from a wide array of neurological disorders ( Khodaparast et al, 2013 , 2014 ; Hays et al, 2014b , 2016 ; Dawson et al, 2016 , 2021 ; Pruitt et al, 2016b , 2021 ; Ganzer et al, 2018 ; Kilgard et al, 2018 , 2021 ; Kimberley et al, 2018 ; Meyers et al, 2018 , 2019 ; Darrow et al, 2020a , b , 2021 ) by increasing synaptic plasticity in central networks activated by rehabilitation ( Porter et al, 2012 ; Hulsey et al, 2016 , 2019 ; Meyers et al, 2018 ; Morrison et al, 2019 , 2021 ; Tseng et al, 2020 ). This enhancement of synaptic plasticity is mediated by coordinated action of cholinergic, noradrenergic, and serotonergic systems ( Dorr, 2006 ; Roosevelt et al, 2006 ; Nichols et al, 2011 ; Hulsey et al, 2017 ).…”

“…Vagus nerve stimulation (VNS) paired with rehabilitation has emerged as a therapeutic strategy to enhance recovery in a range of neurological disorders, including stroke ( Khodaparast et al, 2013 , 2014 ; Hays et al, 2014b , 2016 ; Dawson et al, 2016 , 2021 ; Kilgard et al, 2018 ; Kimberley et al, 2018 ; Meyers et al, 2018 ; Pruitt et al, 2021 ), traumatic brain injury ( Pruitt et al, 2016b ), neuropathy ( Meyers et al, 2019 ; Darrow et al, 2020a , 2021 ), spinal cord injury (SCI; Ganzer et al, 2018 ; Darrow et al, 2020b ; Kilgard et al, 2021 ), and post-traumatic stress disorder (PTSD; George et al, 2008 ; Pena et al, 2014 ; Noble et al, 2017 ; Kilgard et al, 2020 ; Souza et al, 2020 ). Following a recently completed pivotal study, VNS paired with rehabilitation has received United States FDA approval as the first neuromodulation therapy for chronic stroke ( Dawson et al, 2021 ; FDA, 2021 ).…”

Rebuilding Body–Brain Interaction from the Vagal Network in Spinal Cord Injuries

“…In addition, long-term active VNS paired with rehabilitation training can benefit the functional recovery of patients following ischemic stroke [66]. VNS in animal models of spinal or peripheral injury has been demonstrated to improve sensory and motor function of the forelimbs, on combining the stimulation with active rehabilitation training [67][68][69]. A stronger connection has been recorded between the brain and the deafferented muscles, with the possibility of improving the synaptic strength of the spared connections or to create new ones (in continuity with reports on the reinforcement of the connectivity of the corticospinal tract) [67,68].…”