RecruitingNot ApplicableNCT07657260

Investigating the Transcutaneous vs. Transcranial Mechanisms of Trigeminal Nerve Stimulation (eTNS) Using fMRI

Differentiating the Transcutaneous and Transcranial Mechanisms of Direct Current Trigeminal Nerve Stimulation on Brainstem and Autonomic Function: A Randomized, Sham-Controlled, Crossover fMRI Study With Local Anesthesia

Sponsor

Xidian University

Enrollment

25 participants

Start Date

Jun 21, 2026

Study Type

INTERVENTIONAL

Conditions

Healthy Volunteers fMRI Research Neurophysiology

Summary

Transcutaneous Trigeminal Nerve Stimulation (eTNS) is a non-invasive technique that modulates brain activity by applying electrical currents to the forehead. However, it remains unclear whether its effects are primarily driven by activating peripheral nerves in the skin (the transcutaneous pathway) or by the electrical current passing directly through the skull into the brain (the transcranial pathway). This study aims to differentiate these two mechanisms in healthy volunteers. Participants will complete two separate MRI scanning sessions. In one session, a local anesthetic (lidocaine) will be applied to numb the skin over the forehead (specifically the supraorbital nerve branch) to temporarily block the peripheral nerve signals. In the other session, no anesthesia will be used. During both sessions, participants will receive active direct current eTNS (DC-eTNS) and a sham (inactive) stimulation while inside a 3T MRI scanner. Researchers will simultaneously measure brain activity (fMRI) and physiological signals (breathing and heart rate). By comparing the brain and bodily responses between the anesthetized and non-anesthetized conditions, the study seeks to determine exactly how eTNS signals travel to and affect the brainstem, cortex, and autonomic nervous system.

Eligibility

Min Age: 18 YearsMax Age: 35 Years

Inclusion Criteria5

Healthy volunteers, aged 18 to 40 years old.
Right-handed.
Generally healthy with no history of neurological, psychiatric, or severe cardiovascular diseases.
Normal physical and neurological examinations.
Capable of understanding the study procedures and voluntarily signing the written informed consent form.

Exclusion Criteria8

Known allergy, hypersensitivity, or adverse reactions to Lidocaine or other amide-type local anesthetics. (Crucial for this specific study design)
Contraindications to MRI scanning (e.g., claustrophobia, cardiac pacemakers, artificial cochlea, metallic braces, or any other ferromagnetic implants).
Female participants who are pregnant, lactating, or suspect they might be pregnant.
Contraindications to transcranial or transcutaneous electrical stimulation (e.g., personal or family history of epilepsy/seizures, implanted brain stimulators).
Any active skin disease, inflammation, lesions, cuts, or abrasions on the forehead (specifically over the supraorbital area), which could alter electrical impedance or anesthetic absorption.
History of trigeminal neuralgia, facial nerve palsy, or chronic facial pain. Current or recent (within the past month) use of any medications known to affect the central nervous system, autonomic nervous system, or pain perception (e.g., analgesics, antidepressants, beta-blockers, or sedatives).
History of substance abuse, heavy smoking, or excessive daily consumption of alcohol or caffeine.
Irregular sleep patterns, shift work, or severe sleep deprivation within 24 hours prior to the scanning sessions.

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Interventions

DRUGTopical Lidocaine

Application of a local anesthetic over the forehead targeting the supraorbital nerve branch prior to the MRI scan, intended to block peripheral transcutaneous nerve conduction.

DEVICEDirect Current eTNS (DC-eTNS)

Active direct current electrical stimulation applied via electrodes on the forehead. The stimulation is synchronized with a 7-minute and 30-second BOLD fMRI sequence, which includes a 15-second current ramp-up phase at the beginning and a 15-second current ramp-down phase at the end.

DEVICESham DC-eTNS

An inactive or sensory-matched sham stimulation administered during a 7-minute and 30-second BOLD fMRI sequence to serve as a baseline comparator.