Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns

Badran, Bashar W.; Jenkins, Dorothea; DeVries, William H.; Dancy, Morgan; Summers, Philipp M.; Mappin, Georgia; Bernstein, Henry H.; Bikson, Marom; Coker-Bolt, Patricia; George, Mark S.

doi:10.1016/j.brs.2018.06.009

Cited by 25 publications

(14 citation statements)

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“…After obtaining parental consent, we enrolled 14 participants who were consulted for G-tube placement in a prospective, open-label phase 0 trial to determine the feasibility, safety, and potential clinical benefit of a novel taVNS-paired oromotor rehabilitation paradigm in neonates with oromotor dyscoordination. We reported on five of the participants in this trial in an earlier brief communication (Badran et al, 2018b). Our primary clinical outcomes were improved PO feeding volumes and attaining full PO feeds adequate for discharge, thereby avoiding G-tube implantation (Figure 1).…”

Section: Study Overviewmentioning

confidence: 99%

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation for Oromotor Feeding Problems in Newborns: An Open-Label Pilot Study

Badran

Jenkins

Cook

et al. 2020

Front. Hum. Neurosci.

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Neonates born premature or who suffer brain injury at birth often have oral feeding dysfunction and do not meet oral intake requirements needed for discharge. Low oral intake volumes result in extended stays in the hospital (>2 months) and can lead to surgical implant and explant of a gastrostomy tube (G-tube). Prior work suggests pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke, and transcutaneous auricular VNS (taVNS) has emerged as promising noninvasive form of VNS. Pairing taVNS with bottle-feeding rehabilitation may improve oromotor coordination and lead to improved oral intake volumes, ultimately avoiding the need for G-tube placement. We investigated whether taVNS paired with oromotor rehabilitation is tolerable and safe and facilitates motor learning in infants who have failed oral feeding. We enrolled 14 infants [11 premature and 3 hypoxic-ischemic encephalopathy (HIE)] who were slated for G-tube placement in a prospective, open-label study of taVNS-paired rehabilitation to increase feeding volumes. Once-daily taVNS was delivered to the left tragus during bottle feeding for 2 weeks, with optional extension. The primary outcome was attainment of oral feeding volumes and weight gain adequate for discharge without G-tube while also monitoring discomfort and heart rate (HR) as safety outcomes. We observed no adverse events related to stimulation, and stimulation-induced HR reductions were transient and safe and likely confirmed vagal engagement. Eight of 14 participants (57%) achieved adequate feeding volumes for discharge without G-tube (mean treatment length: 16 ± 6 days). We observed significant increases in feeding volume trajectories in responders compared with pre-stimulation (p < 0.05). taVNS-paired feeding rehabilitation appears safe and may improve oral feeding in infants with oromotor dyscoordination, increasing the rate of discharge without G-tube, warranting larger controlled trials.

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Section: Study Overviewmentioning

confidence: 99%

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation for Oromotor Feeding Problems in Newborns: An Open-Label Pilot Study

Badran

Jenkins

Cook

et al. 2020

Front. Hum. Neurosci.

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“…Available data from human studies describing regional brain activation in response to non-invasive VNS varies substantially from study to study (Kraus et al, 2007; Frangos et al, 2015; Yakunina et al, 2017; Badran et al, 2018a). Moreover, human studies using tVNS at the tragus failed to demonstrate significant activation of the locus coeruleus, a key brainstem nucleus in the actions of VNS, compared to sham stimulation (Yakunina et al, 2017; Badran et al, 2018b). These studies may explain the reduced efficacy of human studies with non-invasive VNS compared to cervical VNS (Bauer et al, 2016; Barbella et al, 2018).…”

Section: Non-invasive Vagus Nerve Stimulationmentioning

confidence: 99%

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke

et al. 2019

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Stroke is a leading cause of disability worldwide, and in approximately 60% of individuals, upper limb deficits persist 6 months after stroke. These deficits adversely affect the functional use of the upper limb and restrict participation in day to day activities. An important goal of stroke rehabilitation is to improve the quality of life by enhancing functional independence and participation in activities. Since upper limb deficits are one of the best predictors of quality of life after stroke, effective interventions targeting these deficits may represent a means to improve quality of life. An increased understanding of the neurobiological processes underlying stroke recovery has led to the development of targeted approaches to improve motor deficits. One such targeted strategy uses brief bursts of Vagus Nerve Stimulation (VNS) paired with rehabilitation to enhance plasticity and support recovery of upper limb function after chronic stroke. Stimulation of the vagus nerve triggers release of plasticity promoting neuromodulators, such as acetylcholine and norepinephrine, throughout the cortex. Timed engagement of neuromodulators concurrent with motor training drives task-specific plasticity in the motor cortex to improve function and provides the basis for paired VNS therapy. A number of studies in preclinical models of ischemic stroke demonstrated that VNS paired with rehabilitative training significantly improved the recovery of forelimb motor function compared to rehabilitative training without VNS. The improvements were associated with synaptic reorganization of cortical motor networks and recruitment of residual motor neurons controlling the impaired forelimb, demonstrating the putative neurobiological mechanisms underlying recovery of motor function. These preclinical studies provided the basis for conducting two multi-site, randomized controlled pilot trials in individuals with moderate to severe upper limb weakness after chronic ischemic stroke. In both studies, VNS paired with rehabilitation improved motor deficits compared to rehabilitation alone. The trials provided support for a 120-patient pivotal study designed to evaluate the efficacy of paired VNS therapy in individuals with chronic ischemic stroke. This manuscript will discuss the neurobiological rationale for VNS therapy, provide an in-depth discussion of both animal and human studies of VNS therapy for stroke, and outline the challenges and opportunities for the future use of VNS therapy.

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“…We have recently shown invasive VNS to have beneficial effects on human executive functions, specifically working memory (Sun et al, 2017b ), suggesting that VNS might be useful in the treatment of cognitive impairment. Considering the costs and risks involved in invasive stimulation, it is of great interest to determine whether a safer non-invasive stimulation, transcutaneous vagus nerve stimulation (tVNS; Badran et al, 2018b ; Redgrave et al, 2018 ), has similar potential for enhancing executive functions.…”

Section: Introductionmentioning

confidence: 99%

Reduced Frontal Nogo-N2 With Uncompromised Response Inhibition During Transcutaneous Vagus Nerve Stimulation—More Efficient Cognitive Control?

Pihlaja

Failla

Peräkylä

et al. 2020

Front. Hum. Neurosci.

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We have previously shown invasive vagus nerve stimulation to improve attention and working memory and alter emotion-attention interaction in patients with refractory epilepsy, suggesting that VNS might be useful in the treatment of cognitive impairment. The current research focuses on whether non-invasive, transcutaneous vagus nerve stimulation (tVNS) has similar effects to VNS. Furthermore, we aimed to assess whether tVNS has an impact on cognitive control in general or on underlying brain physiology in a task that mimics everyday life demands where multiple executive functions are engaged while encountering intervening emotional stimuli. Event-related potentials (ERP) evoked in such a task, specifically centro-parietal P3 and frontal N2 were used as biomarkers for attention allocation and cognitive control required to carry out the task. A single-blinded, sham-controlled, within-subject study on healthy subjects ( n = 25) was conducted using Executive Reaction Time Test (RT-test), a Go/NoGo task engaging multiple executive functions along with intervening threat-related distractors while EEG was recorded. tVNS at the left tragus and sham stimulation at the left ear lobe was alternately delivered throughout the task. To assess the impact of tVNS on neural activity underlying attention and cognitive control, centro-parietal P3 and frontal N2 peak amplitudes were measured in Go and NoGo conditions. Task performance was assessed with RTs and different error types reflecting cognitive control in general and distinct executive functions, such as working memory and response inhibition.No significant effects due to tVNS on performance in the Executive RT-test were observed. For N2 there was a main effect of stimulator status and a significant interaction of trial type (Go, NoGo) and stimulator status. Post hoc analysis revealed that tVNS resulted in a significant reduction of frontal N2 only in the NoGo condition. No significant effects were observed for P3 nor were there any effects of emotion. Diminished NoGo-N2 potential along with unaltered task performance during tVNS suggests fewer cognitive control resources were required to successfully withhold a prepotent response. Though caution is warranted, we suggest that tVNS may lead to more efficient neural processing with fewer resources needed for successful cognitive control, providing promise for its potential use in cognitive enhancement.

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Transcutaneous auricular vagus nerve stimulation (taVNS) for improving oromotor function in newborns

Cited by 25 publications

References 10 publications

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation for Oromotor Feeding Problems in Newborns: An Open-Label Pilot Study

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation for Oromotor Feeding Problems in Newborns: An Open-Label Pilot Study

Targeted Vagus Nerve Stimulation for Rehabilitation After Stroke

Reduced Frontal Nogo-N2 With Uncompromised Response Inhibition During Transcutaneous Vagus Nerve Stimulation—More Efficient Cognitive Control?

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