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

15 giugno 2026 aggiornato da: Xidian University

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

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

This is an exploratory, randomized, sham-controlled, crossover functional neuroimaging study designed to isolate and differentiate the transcutaneous (peripheral nerve mediated) versus transcranial (direct electrical penetration) mechanisms of direct current Trigeminal Nerve Stimulation (DC-eTNS).

Healthy participants will undergo two separate study sessions in a randomized order:

Anesthesia Condition: Local anesthesia (Lidocaine) will be applied to the skin area corresponding to the supraorbital branch of the trigeminal nerve to temporarily block somatosensory afferent pathways.

No-Anesthesia Condition: The participant will undergo the same procedures without the application of local anesthesia.

During each session, participants will be scanned in a 3T MRI scanner. The imaging protocol will consist of a high-resolution structural T1-weighted scan, followed by two functional Blood Oxygenation Level-Dependent (BOLD) sequences: one for active DC-eTNS and one for Sham stimulation. Each functional BOLD sequence will last for 7 minutes and 30 seconds. The active DC-eTNS stimulation paradigm includes a 15-second current ramp-up phase at the beginning and a 15-second current ramp-down phase at the end to ensure participant comfort and safety.

Concurrently with the fMRI acquisition, continuous physiological monitoring will be conducted using a respiratory belt and a photoplethysmography (PPG) finger sensor to capture peripheral autonomic nervous system metrics.

Data Analysis Plan:

Primary Analysis: The primary objective is to evaluate the Amplitude of Low-Frequency Fluctuations (ALFF) specifically within the brainstem, focusing on the principal nodes of the trigeminal nerve. The core statistical comparison will assess the contrast of (DC-eTNS - Sham) under the No-Anesthesia condition versus (DC-eTNS - Sham) under the Anesthesia condition.

Secondary Analyses: Secondary neuroimaging analyses will investigate changes in dynamic and static functional connectivity between the brainstem nuclei and cortical regions, as well as whole-brain cortical activation disparities between the two sensory states.

Physiological and Coupling Analyses: Concurrent respiratory and PPG data will be analyzed to detect variations in autonomic nervous system activity (e.g., Heart Rate Variability). Furthermore, central-autonomic coupling indices will be calculated to examine how the different transmission pathways of DC-eTNS modulate the synchronization between central neural networks and peripheral autonomic output.

Tipo di studio

Interventistico

Iscrizione (Stimato)

25

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Cina
    • Shaanxi
      • Xi'an, Shaanxi, Cina, 71000
        • Reclutamento
        • Xidian University
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto

Accetta volontari sani

Sì

Descrizione

Inclusion Criteria:

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

Exclusion Criteria:

  1. Known allergy, hypersensitivity, or adverse reactions to Lidocaine or other amide-type local anesthetics. (Crucial for this specific study design)
  2. Contraindications to MRI scanning (e.g., claustrophobia, cardiac pacemakers, artificial cochlea, metallic braces, or any other ferromagnetic implants).
  3. Female participants who are pregnant, lactating, or suspect they might be pregnant.
  4. Contraindications to transcranial or transcutaneous electrical stimulation (e.g., personal or family history of epilepsy/seizures, implanted brain stimulators).
  5. 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.
  6. 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).
  7. History of substance abuse, heavy smoking, or excessive daily consumption of alcohol or caffeine.
  8. Irregular sleep patterns, shift work, or severe sleep deprivation within 24 hours prior to the scanning sessions.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione incrociata
  • Mascheramento: Separare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Lidocaine Anesthesia Session
In this crossover phase, participants will have a local anesthetic (Lidocaine) applied to the skin over the supraorbital branch of the trigeminal nerve to temporarily block somatosensory afferent pathways. Following the anesthesia, participants will undergo a 3T fMRI scan, during which they will receive both active Direct Current eTNS (DC-eTNS) and a Sham stimulation. Each stimulation sequence lasts for 7 minutes and 30 seconds.
Droga: Topical 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.
Dispositivo: Direct 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.
Dispositivo: Sham 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.
Comparatore attivo: No-Anesthesia Session
In this crossover phase, participants will NOT receive any local anesthesia. They will undergo the 3T fMRI scan with intact somatosensory pathways. Similar to the other arm, they will receive both active Direct Current eTNS (DC-eTNS) and a Sham stimulation. Each stimulation sequence lasts for 7 minutes and 30 seconds.
Dispositivo: Direct 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.
Dispositivo: Sham 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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Amplitude of Low-Frequency Fluctuations (ALFF) in the Brainstem
Lasso di tempo: Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
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.
Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Brainstem-to-Cortex Functional Connectivity
Lasso di tempo: Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
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.
Computed from the data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
Whole-Brain Cortical Activation Levels
Lasso di tempo: During the 7-minute and 30-second fMRI scan for each stimulation condition.
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.
During the 7-minute and 30-second fMRI scan for each stimulation condition.
Autonomic Nervous System (ANS) Activity Metrics
Lasso di tempo: Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.
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.
Continuously recorded during the 7-minute and 30-second fMRI scan for each stimulation condition.
Central-Autonomic Coupling Index
Lasso di tempo: Computed from the multi-modal data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.
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.
Computed from the multi-modal data acquired during the 7-minute and 30-second fMRI scan for each stimulation condition.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Xidian University

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

21 giugno 2026

Completamento primario (Stimato)

5 luglio 2026

Completamento dello studio (Stimato)

5 luglio 2026

Date di iscrizione allo studio

Primo inviato

15 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

15 giugno 2026

Primo Inserito (Effettivo)

18 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 20260618

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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