Noninvasive VNS to Facilitate Excitability in Motor Cortex

Combining Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) With Transcranial Magnetic Stimulation (TMS) to Enhance Cortical Excitability

Transcranial Magnetic Stimulation (TMS) positively influences motor rehabilitation in stroke recovery. Transcutaneous auricular vagus nerve stimulation (taVNS) has shown effects on cortical plasticity. We investigate whether combination of TMS and taVNS is more effective at motor cortex excitability than either modality alone.

Study Overview

• Status: Completed
• Conditions: Stroke; Stroke Sequelae; Motor Activity
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation; Device: transcutaneous auricular vagus nerve stimulation (taVNS)

Detailed Description

The investigators aim to determine the effects of taVNS on motor cortex excitability. The hypothesis is that taVNS alone (sham rTMS + active taVNS) will induce increases in motor cortex excitability (post-stimulation compared to baseline). The investigators expect these changes will be of a lesser magnitude than those of TMS alone (active rTMS + sham taVNS) due to the indirect mechanistic approach of taVNS. Another aim is to determine whether taVNS-paired TMS is more effective at inducing cortical excitability than TMS alone, as it is hypothesized that pairing two forms of neuromodulation (active rTMS + active taVNS) will increase TMS-induced cortical excitability in the motor cortex when compared to single modality approaches (active rTMS + sham taVNS; sham rTMS + active taVNS). Furthermore, it is expected that this increase is timing sensitive, and the paired approach will induce larger TMS-induced cortical excitability compared to unpaired neuromodulation (active taVNS + active taVNS).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-80
• endorsing good health

Exclusion Criteria:

• no TMS-induced motor cortex excitability changes in response to 20Hz motor cortex rTMS
• active psychiatric or neurological disorders
• history of CNS disease, concussion, overnight hospitalization, or other neurologic sequelae, tumors, seizures, frequent or severe headaches
• metal implanted above the neck
• currently taking seizure reducing medications
• currently taking psychotropic medications
• any psychotropic medication taken within 5 half-lives of procedure time
• abuse or dependence of drugs (excluding nicotine and caffeine)
• currently taking medications that lower the seizure threshold
• taking any of the stimulants, thyroid medication, or steroids
• implanted devices/ferrous metal of any kind
• history of seizure or seizure disorder
• inability to determine motor threshold.
• Pregnant females and children under the age of 18 will be excluded for safety reasons
• No vulnerable populations or special classes of subjects will be considered for participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMS combined with taVNS	Device: Transcranial Magnetic Stimulation; transcranial magnetic stimulation delivers magnetic pulses to the brain through the scalp/skull; Device: transcutaneous auricular vagus nerve stimulation (taVNS); non-invasive vagus nerve stimulation delivers electricity to the ear

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Combined taVNS and TMS	We will monitor and record adverse events of combined taVNS TMS intervention.	every 10 minutes following for 30 minutes

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2020
• Primary Completion (Actual): June 12, 2023
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: stroke; recovery; motor cortex; TMS; motor; VNS
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 00089851

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share data except through peer-review.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes