Ear Stimulation for Brain Activity

Overseen By Bashar W Badran, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Olanzapine, Chlorpromazine, Lithium, others

Disqualifiers: Seizure, Epilepsy, Psychosis, Mania, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

96 Participants Needed

Trial Summary

What is the purpose of this trial?

In this one-visit, randomized, double-blind, sham-controlled trial, we plan to use a novel concurrent transcutaneous auricular neurostimulation (tAN) paradigm during functional magnetic resonance imaging (fMRI) paradigm in 96 individuals to determine whether tAN administered to two cranial nerves simultaneously produces greater neurophysiologic effects than stimulating solely to the auricular branch of the vagus nerve (ABVN) or the auriculotemporal nerve (ATN; branch of trigeminal nerve) alone. Within the MRI scanner, each participant will be connected to a series of electrodes that stimulate 4 targets (ABVN only, ATN only, ABVN plus ATN, and Sham).

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, chlorpromazine, or lithium.

What data supports the effectiveness of the treatment tAN, Transcutaneous Auricular Neurostimulation, tAN?

Research on similar treatments, like transcutaneous auricular vagus nerve stimulation (taVNS), shows that applying electrical currents to the ear can activate brain areas related to hearing and emotions. This suggests that tAN might also influence brain activity, potentially helping with conditions like tinnitus. ^{1 2 3 4 5}

Is ear stimulation for brain activity safe for humans?

Ear stimulation, specifically transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe for humans. Most studies report only mild and temporary side effects like ear pain, headache, and tingling, with no severe adverse events linked to the treatment. ^{1 2 6 7 8}

How is the treatment tAN different from other treatments for brain activity?

Transcutaneous Auricular Neurostimulation (tAN) is unique because it uses electrical stimulation applied to the ear to activate the vagus nerve, potentially influencing brain activity through non-invasive means. This approach is different from other treatments as it targets the auricular branch of the vagus nerve, which may activate specific pathways in the brain without the need for medication. ^{2 3 4 9 10}

Eligibility Criteria

This trial is for individuals aged 18-65 who can consent to participate. It's not suitable for those with frequent/severe headaches, contraindications for MRI, untreated medical/neurological/psychiatric conditions, psychosis or mania history, metal implants in head/heart/neck, brain surgery or heart issues history, seizure risk factors like family history or certain medications use, significant head injury history, substance abuse problems or if pregnant.

Inclusion Criteria

I am between 18 and 65 years old.

I can make my own medical decisions and sign consent forms.

Exclusion Criteria

I often have severe headaches.

I have had a serious head injury or concussion in the past.

I have had a heart attack or irregular heartbeat.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants undergo a one-visit, randomized, double-blind, sham-controlled trial involving transcutaneous auricular neurostimulation (tAN) during fMRI

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• tAN

Trial Overview The study tests the effects of transcutaneous auricular neurostimulation (tAN) on two cranial nerves during an fMRI scan. Participants will be randomly assigned to receive tAN targeting different nerve combinations (vagus nerve alone, trigeminal branch alone, both together) versus a sham (fake stimulation), to see which has greater neurological impact.

Participant Groups

Group I: Auricular Neurostimulation (Active 3) 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 -Combo stimulation (stimulation of both the 15Hz cymba conchae and 100HZ tragus)

Group II: 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 -ATNS Only stimulation (100Hz stimulation of the tragus)

Group III: 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 -ABVN Only stimulation (15Hz stimulation of cymba conchae)

Group IV: 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)

Group V: Auricular Neurostimulation (Sham 2) 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 (100Hz stimulation of the earlobe)

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

In a study involving 50 young adults, transcutaneous auricular nerve stimulation (taNS) at 130 µA significantly decreased cardiac output, with distinct gender-related responses observed: women experienced a drop in heart rate, while men showed reductions in stroke volume and contractility.

The findings suggest that the taNS protocol may have potential for modulating cardiac autonomic responses, but further research is needed to explore its therapeutic applications in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic responses to low-level transcutaneous auricular nerve stimulation in young volunteers. Šinkovec, M., Trobec, R., Kamenski, T., et al.[2023]

Transcutaneous electrical nerve stimulation (TENS) applied to the auricula significantly reduced tinnitus severity and associated anxiety and stress levels in a study of 60 patients, with results showing a notable difference compared to a placebo group.

Both one-ear and two-ear TENS treatments were effective, but there was no significant difference in efficacy between the two methods, indicating that TENS can be a viable treatment option for chronic subjective tinnitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous electrical nerve stimulation (TENS) on chronic subjective tinnitus. Tutar, B., Atar, S., Berkiten, G., et al.[2020]

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 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]

Transauricular vagus nerve stimulation (taVNS) at specific auricular acupoints (CO10-12, TF4) effectively activates brain regions associated with auditory processing and emotional regulation, as shown by significant changes in blood oxygenation level dependent (BOLD) signals in a study of 24 healthy subjects.

The study suggests that taVNS could be a promising treatment for tinnitus, as it demonstrated the ability to stimulate key areas of the brain involved in hearing and emotional response, indicating its potential therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI. Peng, L., Mu, K., Liu, A., et al.[2022]

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) 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]

In a pilot study involving 46 patients with acute tinnitus, those receiving verum TENS showed significant symptom relief after 4 weeks, as indicated by improvements in the Tinnitus Severity Scale, Tinnitus Questionnaire, and Tinnitus Handicap Inventory.

The study found no adverse events related to TENS treatment, suggesting it is a safe option for managing acute tinnitus symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Randomized Controlled Trial of Transcutaneous Electrical Nerve Stimulation for Patients With Acute Tinnitus. Li, L., Shi, H., Wang, M.[2021]

Auricular stimulation can trigger acute pupillary responses (PRs), indicating that it may activate noradrenergic pathways in the brain, which are important for therapeutic effects.

The study involved 19 participants and found that higher pulse amplitudes and frequencies led to stronger and quicker pupillary responses, particularly when stimulating the canal area of the ear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans. Urbin, MA., Lafe, CW., Simpson, TW., et al.[2021]

Transcutaneous electrical stimulation of the anterior part of the left outer auditory canal effectively activates specific vagal afferents, as indicated by significant decreases in BOLD signals in key brain regions associated with the vagus nerve, suggesting a targeted method for CNS stimulation.

In contrast, stimulation of the posterior part of the auditory canal resulted in less specific changes in brain activity, indicating that the anterior stimulation may be more effective for therapeutic applications in psychiatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study. Kraus, T., Kiess, O., Hösl, K., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Hemodynamic responses to low-level transcutaneous auricular nerve stimulation in young volunteers. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous electrical nerve stimulation (TENS) on chronic subjective tinnitus. [2020]

3. Singapore pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

A Pilot Randomized Controlled Trial of Transcutaneous Electrical Nerve Stimulation for Patients With Acute Tinnitus. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study. [2016]