Investigating the Transcutaneous vs. Transcranial Mechanisms of Trigeminal Nerve Stimulation (eTNS) Using fMRI
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-35
SponsorXidian University
About this trial
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 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
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).
Trial design
Design model
Crossover
Treatments tested in this trial
Topical Lidocaine
DrugApplication of a local anesthetic over the forehead targeting the supraorbital nerve branch prior to the MRI scan, intended to block peripheral transcutaneous nerve conduction.
Direct Current eTNS (DC-eTNS)
DeviceActive 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.
Sham DC-eTNS
DeviceAn inactive or sensory-matched sham stimulation administered during a 7-minute and 30-second BOLD fMRI sequence to serve as a baseline comparator.
Treatment groups
25 Participants
are divided into 2 treatment groupsGroup A: Lidocaine Anesthesia SessionExperimental treatment 3 interventions
Group B: No-Anesthesia SessionActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Amplitude of Low-Frequency Fluctuations (ALFF) in the Brainstem
The primary neuroimaging metric is the ALFF of the BOLD signal, specifically targeting the brainstem regions that encompass the primary nodes of the trigeminal nerve. To differentiate the transcutaneous and transcranial mechanisms, the core statistical analysis will evaluate the interaction effect by comparing the ALFF contrast of (DC-eTNS minus Sham) in the No-Anesthesia condition against the contrast of (DC-eTNS minus Sham) in the Anesthesia (Lidocaine) condition.
Time frame
Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.Secondary outcomes
1
Brainstem-to-Cortex Functional Connectivity
The strength of functional connectivity between the targeted brainstem nuclei and widespread cortical regions. Connectivity maps will be calculated and compared between the Anesthesia and No-Anesthesia conditions across the active DC-eTNS and Sham phases to evaluate how blocking peripheral pathways alters neural network communication.
Time frame
Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.2
Whole-Brain Cortical Activation Levels
Differences in whole-brain BOLD signal activation and deactivation patterns. This will assess the overall cortical response to DC-eTNS and determine how these activation levels are modulated when the peripheral somatosensory afferent pathways are temporarily blocked by local anesthesia.
Time frame
During the 7-minute and 30-second fMRI scan for each stimulation condition.3
Autonomic Nervous System (ANS) Activity Metrics
Peripheral autonomic physiological changes assessed via continuous respiratory belt and photoplethysmography (PPG) signals. Key parameters include Heart Rate Variability (HRV) indices (e.g., LF/HF ratio, RMSSD) and respiratory amplitude/rate. The variations in these metrics will be compared between the Anesthesia and No-Anesthesia states during DC-eTNS and Sham.
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 (coupling) between central neural activity (BOLD signal fluctuations in brainstem/cortical regions) and peripheral autonomic outputs (HRV and respiratory signals). This metric aims to reveal whether the transcutaneous or transcranial pathway is the primary driver of central-autonomic integration during DC-eTNS.
Time frame
Computed from the multi-modal data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.Sponsors and contacts
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Source ClinicalTrials.gov