Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke

Abstract

Implanted vagus nerve stimulation (VNS) delivered concurrently with upper limb rehabilitation has been shown to improve arm function after stroke. Transcutaneous auricular VNS (taVNS) offers a non-invasive alternative to implanted VNS and may provide similar therapeutic benefit. There is much discussion about the optimal approach for combining VNS and physical therapy, as such we sought to determine whether taVNS administered during robotic training, specifically delivered during the premotor planning stage for arm extension movements, would confer additional motor improvement in patients with chronic stroke. Thirty-six patients with chronic, moderate-severe upper limb hemiparesis (>6 months; mean Upper Extremity Fugl-Meyer score = 25 ± 2, range 13–48), were randomized to receive 9 sessions (1 h in length, 3x/week for 3 weeks) of active (N = 18) or sham (N = 18) taVNS (500 ms bursts, frequency 30 Hz, pulse width 0.3 ms, max intensity 5 mA, ∼250 stimulated movements per session) delivered during robotic training. taVNS was triggered by the onset of a visual cue prior to center-out arm extension movements. Clinical assessments and surface electromyography (sEMG) measures of the biceps and triceps brachii were collected during separate test sessions. Significant motor improvements were measured for both the active and sham taVNS groups, and these improvements were robust at 3 month follow-up. Compared to the sham group, the active taVNS group showed a significant reduction in spasticity of the wrist and hand at discharge (Modified Tardieu Scale; taVNS = –8.94% vs. sham = + 2.97%, p < 0.05). The EMG results also demonstrated significantly increased variance for the bicep peak sEMG amplitude during extension for the active taVNS group compared to the sham group at discharge (active = 26.29% MVC ± 3.89, sham = 10.63% MVC ± 3.10, mean absolute change admission to discharge, p < 0.01), and at 3-month follow-up, the bicep peak sEMG amplitude was significantly reduced in the active taVNS group (P < 0.05). Thus, robot training improved the motor capacity of both groups, and taVNS, decreased spasticity. taVNS administered during premotor planning of movement may play a role in improving coordinated activation of the agonist-antagonist upper arm muscle groups by mitigating spasticity and increasing motor control following stroke.Clinical Trial Registration:www.ClinicalTrials.gov, identifier (NCT03592745).

Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor

“…The similar results are shown in other studies about non-invasive VNS. Transcutaneous auricular VNS, applied noninvasively to the peripheral auricular branch of the VS, can also improve the upper limb motor function of the patients suffered from cerebral I/R injury [ 36 – 38 ]. Furthermore, it has been suggested that sensor function can be significantly improved in chronic stroke patients following VNS treatment paired with the conventional rehabilitation [ 39 , 40 ].…”

Efficacy and Safety of Vagus Nerve Stimulation on Upper Limb Motor Recovery After Stroke. A Systematic Review and Meta-Analysis

“…Chang et al (44) is the most recent study that evaluated the efficacy of the transcutaneous auricular VNS on the upper limb motor function. In this clinical trial, the authors included 34 patients with unilateral supratentorial chronic (>6 months) stroke.…”

“…The risk of bias assessment was applied to the six clinical trials (Dawson et (34,43,44,46,47,49) upon which the initial meta-analysis for the assessment of VNS efficacy for motor rehabilitation was based. All studies had low risk of bias in the selective reporting domain.…”

“…There have been multiple clinical studies that have evaluated the safety and efficacy of implanted and transcutaneous VNS in the recovery of motor function after stroke (34,(43)(44)(45)(46)(47)(48)(49), and recently, meta-analyses have suggested that VNS has a positive effect on upper limb function in stroke patients (50)(51)(52), however these reviews did not evaluate the effect vagus nerve stimulation according to time since stroke. The aim of this systematic review is to summarize and analyze the scientific evidence of the safety and efficacy of both implanted and transcutaneous VNS for the management of upper limb motor impairment after stroke.…”

Vagus nerve stimulation paired with rehabilitation for motor function, mental health and activities of daily living after stroke: a systematic review and meta-analysis

“…Accumulating clinical trials favoured VNS+Rehab for improving upper limb function in patients after a stroke 18–25. To date several meta-analyses have combined the effects of VNS+Rehab on upper limb function in patients who had a stroke and demonstrated that VNS might be beneficial for upper limb function recovery 26–28.…”