Frequency Effects of Transcutaneous Trigeminal Nerve Stimulation (eTNS) on Brain and Autonomic Function

NCT07662291 | Recruiting

• 1 other identifier: 20260617
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate how different frequencies of transcutaneous Trigeminal Nerve Stimulation (eTNS) affect brain activity and the autonomic nervous system in healthy individuals. Participants will undergo a 3T functional magnetic resonance imaging (fMRI) scan while receiving three different types of nerve stimulation: 2Hz eTNS, 120Hz eTNS, and a sham (inactive) stimulation. The order of these stimulations will be randomly assigned. During the brain scan, researchers will simultaneously monitor the participants' breathing and heart rhythms (using a finger sensor). The main goal is to understand how changing the frequency of eTNS influences the connection between the brain's networks and the body's unconscious physiological responses.

Conditions

Healthy Volunteers; fMRI Research

Keywords

Transcutaneous Trigeminal Nerve Stimulation; eTNS; Neuromodulation; Functional Magnetic Resonance Imaging / fMRI; Functional Connectivity; Frequency Effect; Blood Oxygenation Level-Dependent / BOLD; Central-Autonomic Coupling

Outcome Measures

Primary Outcomes (1)

• Difference in Blood Oxygenation Level-Dependent (BOLD) Signal Amplitude in the Brainstem

  The metric is the percent signal change in BOLD amplitude within predefined Regions of Interest (ROIs) of the brainstem (e.g., trigeminal nuclei, locus coeruleus, nucleus tractus solitarii). It is calculated as the BOLD signal difference between the 30-second stimulation "ON" blocks and the 30-second "OFF" blocks. Data will be aggregated as the mean percentage of BOLD signal change for each stimulation condition.

  During the 7-minute and 30-second fMRI scan for each stimulation condition.

Secondary Outcomes (4)

• Functional Connectivity (FC) within and outside the Central Autonomic Network

  During the 7-minute and 30-second fMRI scan for each stimulation condition.

• Change in Heart Rate Variability Assessed by Low Frequency to High Frequency (LF/HF) Ratio

  Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.

• Change in Respiratory Rate

  Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.

• Central-Autonomic Coupling Index

  Computed from data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.

Study Arms (3)

2Hz-eTNS Condition

EXPERIMENTAL

In this crossover phase, participants will receive 2Hz transcutaneous Trigeminal Nerve Stimulation (eTNS) during the 3T fMRI scan. The stimulation will be delivered during a 7-minute and 30-second BOLD sequence using a block design, which alternates between 30-second "ON" periods (active 2Hz stimulation) and 30-second "OFF" periods (no stimulation).

Device: 2Hz Transcutaneous Trigeminal Nerve Stimulation

120Hz-eTNS Condition

EXPERIMENTAL

In this crossover phase, participants will receive 120Hz transcutaneous Trigeminal Nerve Stimulation (eTNS) during the 3T fMRI scan. Similar to other active conditions, the stimulation will be delivered during a 7-minute and 30-second BOLD sequence using a block design, alternating between 30-second "ON" periods (active 120Hz stimulation) and 30-second "OFF" periods (no stimulation).

Device: 120Hz Transcutaneous Trigeminal Nerve Stimulation

Sham-eTNS Condition

SHAM COMPARATOR

In this crossover phase, participants will undergo the same fMRI scanning procedure and wear the exact same electrode pads as the active conditions, but will receive a sham stimulation. This phase also lasts for 7 minutes and 30 seconds and utilizes a simulated 30-second "ON" / 30-second "OFF" block design to maintain double-blinding.

Device: Sham Transcutaneous Trigeminal Nerve Stimulation

Interventions

120Hz Transcutaneous Trigeminal Nerve Stimulation DEVICE

Active electrical stimulation applied over the skin of the forehead targeting the branches of the trigeminal nerve. The stimulation frequency is set at 120Hz. It is synchronized with the fMRI sequence and continuous physiological monitoring (respiration and photoplethysmography).

120Hz-eTNS Condition

Sham Transcutaneous Trigeminal Nerve Stimulation DEVICE

An inactive or sensory-matched sham electrical stimulation designed to mimic the physical sensation of the device being active without delivering the therapeutic frequencies (2Hz or 120Hz). It is administered synchronously with the fMRI BOLD sequence and physiological monitoring to serve as a baseline comparator.

Sham-eTNS Condition

2Hz Transcutaneous Trigeminal Nerve Stimulation DEVICE

Active electrical stimulation applied over the skin of the forehead targeting the branches of the trigeminal nerve. The stimulation frequency is set at 2Hz. It is synchronized with the fMRI sequence and continuous physiological monitoring (respiration and photoplethysmography).

2Hz-eTNS Condition

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 transcutaneous electrical stimulation (e.g., personal or family history of epilepsy/seizures, trigeminal neuralgia, facial skin lesions, or active skin diseases on the forehead).
• Current or recent (within the past month) use of any medications known to affect the central nervous system or the autonomic nervous system (e.g., antidepressants, beta-blockers, sedatives, or sympathomimetics).
• 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 session.

Sponsors & Collaborators

• Xidian University: lead

Study Sites (1)

Xidian University

Xi'an, Shaanxi, 71000, China

RECRUITING

Central Study Contacts

Xue-Juan Yang

CONTACT

13227038185; xjyang@xidian.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 23, 2026
• Study Start (Estimated): August 6, 2026
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): August 20, 2026
• Last Updated: June 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)