Frequency Effects of Transcutaneous Trigeminal Nerve Stimulation (eTNS) on Brain and Autonomic Function
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-35
SponsorXidian University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Crossover
Treatments tested in this trial
2Hz Transcutaneous Trigeminal Nerve Stimulation
DeviceActive 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).
120Hz Transcutaneous Trigeminal Nerve Stimulation
DeviceActive 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).
Sham Transcutaneous Trigeminal Nerve Stimulation
DeviceAn 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.
Treatment groups
25 Participants
are divided into 3 treatment groupsGroup A: 2Hz-eTNS ConditionExperimental treatment 1 intervention
Group B: 120Hz-eTNS ConditionExperimental treatment 1 intervention
Group C: Sham-eTNS ConditionSham comparator 1 intervention
Trial outcomes
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.
Time frame
During the 7-minute and 30-second fMRI scan for each stimulation condition.Secondary outcomes
1
Functional Connectivity (FC) within and outside the Central Autonomic Network
The strength of dynamic and static functional connectivity between key nodes of the CAN and other whole-brain regions. Connectivity matrices will be computed and compared across the 2Hz-eTNS, 120Hz-eTNS, and Sham conditions to evaluate how different stimulation frequencies modulate brain network communications.
Time frame
During the 7-minute and 30-second fMRI scan for each stimulation condition.2
Change in Heart Rate Variability Assessed by Low Frequency to High Frequency (LF/HF) Ratio
The LF/HF ratio is a frequency-domain measure of heart rate variability derived from PPG data, reflecting the sympathovagal balance. Data will be aggregated as the mean LF/HF ratio during each stimulation condition.
Time frame
Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.3
Change in Respiratory Rate
Respiratory rate is extracted from concurrent respiratory belt signals to assess respiratory patterns. Data will be aggregated as the mean respiratory rate (measured in breaths per minute) during each stimulation condition.
Time frame
Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.4
Central-Autonomic Coupling Index
The degree of synchronization between central neural activity and peripheral autonomic output. This will be quantified by calculating the correlation coefficients or mutual information between the low-frequency fluctuations of the BOLD signals in CAN regions and the concurrent peripheral autonomic time-series data (HRV and respiration). The coupling strength will be compared between the 2Hz and 120Hz conditions.
Time frame
Computed from data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov