Ear Stimulation for Brain Activity

Overseen By Falon Sutton

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Seizure threshold reducers

Disqualifiers: MRI contraindications, Metal implants, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 30 minutes

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether stimulating different parts of the outer ear can alter brain function using transcutaneous auricular vagus nerve stimulation (taVNS). Researchers will observe brain reactions by analyzing images taken during the process. Participants are divided into groups: some receive real ear stimulation, while others receive a sham for comparison. Individuals who are generally healthy and can undergo an MRI scan are suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on brain function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use medications that lower the seizure threshold, like olanzapine or lithium.

What prior data suggests that this ear stimulation technique is safe?

Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe. Studies indicate that side effects are usually mild and short-lived. This applies to both types of ear stimulations being tested: one on the outer ear and one behind the ear. People without heart problems can use taVNS safely, and it has been used in other studies without serious issues. Overall, taVNS is considered a non-invasive and well-tolerated method. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcutaneous Auricular Neurostimulation (tAN) because it offers a non-invasive way to stimulate specific areas of the ear to influence brain activity. Unlike conventional treatments that might involve medications or more invasive procedures, tAN uses targeted electrical stimulation to potentially enhance brain function. By focusing on different ear targets, such as the mastoid process and cymba conchae, this method could precisely modulate brain activity. This innovative approach might pave the way for new strategies in managing neurological conditions, offering a fresh perspective beyond traditional therapies.

What evidence suggests that this ear stimulation technique is effective for brain activity?

This trial will compare different forms of transcutaneous auricular neurostimulation (tAN), including active and sham treatments. Research has shown that transcutaneous auricular vagus nerve stimulation (taVNS), similar to tAN, can help with various conditions. Studies have found that taVNS improves sleep quality for people with insomnia and reduces related symptoms. One study suggested that taVNS boosts cognitive flexibility, helping the brain switch between different thoughts more easily. Additionally, taVNS has been linked to increased activity in brain areas responsible for complex thinking. Overall, these findings suggest that taVNS may benefit brain and mental health. ^{5 6 7 8 9}

Who Is on the Research Team?

Xiaolong Peng

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for 24 healthy individuals interested in participating in a study to explore brain activation. Participants will undergo non-invasive ear stimulation while their brain images are taken using MRI.

Inclusion Criteria

I can understand and sign the consent form in English by myself.

Exclusion Criteria

I have had brain surgery in the past.

Pregnancy

I have an ear infection, skin irritation, or abnormal ear anatomy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive transcutaneous auricular vagus nerve stimulation (taVNS) at different ear sites while undergoing MRI scanning

30 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Auricular Neurostimulation (tAN)

Trial Overview

The study is testing the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on different outer parts of the ear and how it influences brain activity as seen on MRI scans.

How Is the Trial Designed?

Group I: Auricular Neurostimulation (Active 2) Active Control 1 Intervention

•Within the MRI scanner, each participant will be connected to a series of tAN electrodes that stimulate the following ear target -Mastoid stimulation (15Hz stimulation of mastoid process)

Group II: Auricular Neurostimulation (Active 1) Active Control 1 Intervention

•Within the MRI scanner, each participant will be connected to a series of tAN electrodes that stimulate the following ear target -Cymba stimulation (15Hz stimulation of cymba conchae)

Group III: Auricular Neurostimulation (Sham 1) Placebo Group 1 Intervention

•Within the MRI scanner, each participant will be connected to a series of tAN electrodes that stimulate the following ear target -Sham (15Hz stimulation of the earlobe)

Transcutaneous Auricular Neurostimulation (tAN) is already approved in United States for the following indications:

Approved in United States as Transcutaneous Auricular Neurostimulation (tAN) for:

• Relief of opioid withdrawal symptoms

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

The study demonstrates that millimeter wave (MMW) stimulation can selectively activate the auricular branch of the vagus nerve (ABVN) without affecting nearby non-vagal nerves, as shown by significant increases in local field potential (LFP) power in the nucleus tractus solitarii (NTS) during targeted stimulation.

In contrast, non-vagal nerve stimulation resulted in decreased LFP power, indicating that MMW can effectively differentiate between vagal and non-vagal responses, paving the way for a new clinical treatment approach for conditions like depression and epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. Song, HY., Shin, DW., Jung, SM., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and well-tolerated method for treating conditions like drug-resistant epilepsy, but a recent randomized double-blind trial found no significant difference in outcomes between high- and low-stimulation groups.

The most common side effect of taVNS is a tingling sensation or pain at the stimulation site, and while it shows promise, further research is needed to fully understand its efficacy and to potentially gain approval for insurance coverage in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. Yamamoto, T.[2022]

This study will investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 15 patients with a minimally conscious state, using five different frequencies (1, 10, 25, 50, and 100 Hz) to determine the optimal stimulation parameters.

The goal is to achieve stable improvements in consciousness levels in patients with disorders of consciousness by optimizing the taVNS neuromodulation technique, with results measured through the coma recovery scale-revised (CRS-R) and resting EEG assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. Zhai, W., Jiao, H., Zhuang, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive treatment method that applies electrical current to the outer ear to stimulate the vagus nerve, which has been explored for its therapeutic potential in various diseases.

Over the past two decades, taVNS has gained attention as an alternative to drug treatments, but the field also faces limitations that need to be addressed for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. Wang, Y., Li, SY., Wang, D., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) is a promising non-invasive alternative to traditional vagus nerve stimulation (VNS) for treating conditions like epilepsy and depression, which can be invasive and have side effects.

There is ongoing research into the best stimulation parameters and sites for tVNS, particularly focusing on stimulation at the outer ear, to optimize its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. Hilz, MJ., Bolz, A.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10133680/

Randomized trial of transcutaneous auricular vagus nerve ...

Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS ...

2.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2828072

Transcutaneous Auricular Vagus Nerve Stimulation for ...

Previous studies have demonstrated that taVNS cannot only effectively improve sleep quality in patients with insomnia, but also alleviate accompanying symptoms ...

3.

nature.com

nature.com/articles/s41598-025-17821-5

The effects of non-invasive transcutaneous auricular vagus ...

Our results suggest that taVNS increases homeostatic low-frequency oscillatory activity mainly over the right frontal hemisphere. Active taVNS ...

4.

frontiersin.org

frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2025.1569472/full

Impact of transcutaneous auricular vagus nerve stimulation ...

Conclusion: The findings suggest that taVNS enhances cognitive flexibility, especially in more complex tasks, providing a better understanding ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S1876201824001722

An fMRI-based machine learning analysis

This study showed that taVNS produced promising clinical efficacy in the treatment of mild and moderate MDD. Eleven FCs were selected out and were found to be ...

6.

nature.com

nature.com/articles/s41598-022-25864-1

Safety of transcutaneous auricular vagus nerve stimulation ...

Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11841445/

A pooled analysis of the side effects of non-invasive ...

These findings demonstrate a favorable safety profile of taVNS, with mostly mild and transient effects, supporting its use as a suitable non-invasive tool.

8.

frontiersin.org

frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1405310/full

Current status of transcutaneous auricular vagus nerve ...

According to data, persons without a history of heart disease can safely use taVNS. 2.2 taVNS attenuates tinnitus-triggered stress reaction: a ...

9.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1155/2020/8841752

Effect and Safety of Transcutaneous Auricular Vagus Nerve ...

At the endpoint, the FMA-U, WMFT, and FIM scores were significantly higher than before treatment (P < 0.05), and there was a significantly ...