Noninvasive Vagus Nerve Stimulation (VNS) for Neuromotor Adaptations

NCT ID: NCT03628976

Last Updated: 2022-09-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2021-06-28

Brief Summary

The study will examine how electrical stimulation of vagus nerve (i.e. nerve around the outer ear) from the skin surface during motor training influences a brain hormone (called norepinephrine), brain activity, and motor performance.

Detailed Description

Motor function is compromised with advanced age, and motor impairment is involved in various neuromotor injuries and disorders including stroke, spinal cord injury, amputation, and aging. Development of effective interventions for facilitating neuromotor adaptation is essential for accelerating or augmenting rehabilitation outcomes in the control of impaired limbs. The ultimate goal of the study is to find non-pharmacological and non-invasive neuromodulating interventions for enhancing the rehabilitation outcomes that may be applied to individuals with impaired motor function. In rats, implanted afferent vagus nerve stimulation paired with motor training enhanced neuromotor adaptation and motor recovery most likely through increased release of central neuromodulators that originate from the brainstem. The investigators propose to translate the findings in rats into humans by applying vagus nerve stimulation noninvasively. Transcutaneous VNS (tVNS) can noninvasively activate the brainstem including locus coeruleus, where norepinephrine (i.e. neuromodulator) is synthesized. However, it is unknown whether tVNS leads to increasing neuromodulators and facilitating neuromotor adaptations when combined with motor training in humans. With potential applicability of this novel intervention for facilitating neuromotor adaptation to various clinical human populations in future scope, it is essential to start with the basic understanding about the effect of tVNS on the neuromotor system and training-induced adaptation in neuromotor behavior in non-disabled humans. The overarching hypothesis is that an application of tVNS increases central norepinephrine and facilitates training-induced neuromotor adaptations in humans. The specific aim is to examine the effect of tVNS on central norepinephrine and training-induced neuromotor adaptations in humans. The effect of applying tVNS concurrently to visuomotor training will be investigated by comparing the changes in central norepinephrine and changes in the visuomotor skill and corticospinal excitability due to training with and without tVNS (sham) in non-disabled humans. The visuomotor skill will be assessed with the root-mean-square error of the produced force against the target force, which will be normalized to the maximal voluntary contraction force (MVC) . The investigators expect that subjects with concurrent tVNS during training show greater increases in the visuomotor skill and corticospinal excitability after training. The investigators also expect that tVNS increases central norepinephrine, and the amount of neuromotor adaptations due to training is associated with that of tVNS-induced increase in central norepinephrine. These expected findings will be the first evidence on the efficacy of concurrent tVNS with motor training for upregulating central norepinephrine and facilitating training-induced neuromotor adaptations in humans. They will open new scientific and clinical fields of study that will lead to the creation of motor rehabilitation paired with tVNS that can enhance rehabilitation outcomes in individuals with motor impairment. Demonstration of associated changes between central norepinephrine and neuromotor adaptations due to tVNS in non-disabled humans is a necessary step for applying tVNS to rehabilitation with the understanding of the underlying mechanism and for potentially using central norepinephrine as a predictor of tVNS efficacy in rehabilitation.

Conditions

Healthy Young Adults

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Sham-tVNS to ear lobe

Sham-tVNS will be applied to the ear lobe.

Group Type: SHAM_COMPARATOR

tVNS

Intervention Type: OTHER

Intervention

Motor training

Intervention Type: OTHER

Same finger training for both arms

tVNS to tragus

tVNS will be applied to the tragus.

Group Type: ACTIVE_COMPARATOR

tVNS

Intervention Type: OTHER

Intervention

Motor training

Intervention Type: OTHER

Same finger training for both arms

Interventions

tVNS

Intervention

Intervention Type: OTHER

Motor training

Same finger training for both arms

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Men and women in the age range of 18-39 years will be recruited. All subjects will be healthy and right-handed. Subjects will match the ethnic distribution in the local community.

Exclusion Criteria

• To ensure the safety associated with TMS and transcutaneous afferent vagus nerve stimulation, following adults will be excluded as in our previous studies (Buharin et al. 2013, 2014) and following the standard recommendations (Keel et al. 2001):

1. Younger than 18 years old or older than 39 years old

2. Left-handed

3. Skilled use of hands (e.g. professional musician)

4. High blood pressure (>140/90 mmHg)

5. Had cardiovascular problems

6. Obese (Body Mass Index: > 30 kg/m2)

7. Had sensory deficits in your limb

8. Had alcoholism

9. Had psychiatric disorders

10. Had an adverse reaction to TMS (a technique for non-invasive neural stimulation from the brain)

11. Had a seizure (an abnormal phenomenon of the brain marked by temporary abnormal neuronal activity. Symptoms include involuntary changes in body movement or function, sensation, awareness, or behavior.)

12. Someone in your family has epilepsy (recurrent seizures marking excessive synchronous neuronal activity in the brain)

13. Had an EEG (measurement of the electrical activity of the brain through the use of surface electrodes placed on the scalp) for clinical diagnosis

14. Had a stroke (the loss of brain function due to an interruption in the blood supply to the brain)

15. Had a head injury (include neurosurgery) that required a visit to a hospital

16. Suffer from frequent or severe headaches (e.g., migraine headaches within the last six months)

17. Have any metal permanently in your head (outside the mouth) such as shrapnel, surgical clips, or fragments from welding or metal work. Piercings and other metals on your head are OK if they will be removed before the study.

18. Have any implanted devices such as cardiac pacemakers (a medical device that uses electrical signals to regulate heart beat), medical pumps, or intra-cardiac lines

19. Had any other brain-related condition

20. Had any illness that caused brain injury (i.e. meningitis, aneurysm, brain tumor)

21. Had severe disease such as cardiologic, pulmonary, renal, endocrinal (hyperthyroidism or hypothyroidism), gastrointestinal or others.

22. Taking any medications other than over-the-counter medicine

23. Suspect you might be pregnant (if woman)

24. Have hearing problems, such as impaired hearing, tinnitus, etc.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Georgia Institute of Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Minoru Shinohara, PhD

Role: PRINCIPAL_INVESTIGATOR

Georgia Institute of Technology

Locations

Human Neuromuscular Physiology Lab

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R03NS106088-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H18151

Identifier Type: -

Identifier Source: org_study_id