Healthy ParticipantsNCT07668167
Combined Regulatory Effects of 40 Hz eTNS and Multisensory Stimulation on Brain Networks
A study testing 40 Hz External Trigeminal Nerve Stimulation, 40 Hz Auditory Stimulation and 40 Hz Visual Stimulation in people with Healthy Participants, run by Xidian University at 1 site in China.
Trial summary
The purpose of this study is to investigate the independent and interactive effects of 40Hz auditory, visual, and external trigeminal nerve stimulation (eTNS) on brain state dynamics and functional connectivity. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Participants
- What is being tested?
- 40 Hz External Trigeminal Nerve Stimulation, 40 Hz Auditory Stimulation and 40 Hz Visual Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 16 Jun 2026to 23 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy adults aged ≥18 years old.
- Normal or corrected-to-normal vision and hearing (essential for 40Hz visual and auditory stimulation).
- Right-handedness.
- Willing to participate in the study and capable of providing written informed consent.
Who cannot join
- Personal or family history of epilepsy or seizures (crucial safety criteria for 40Hz flicker and electrical stimulation).
- History of any neurological or psychiatric disorders.
- Presence of metallic implants in the head, cardiac pacemakers, or other implanted electronic medical devices.
- Skin lesions, infections, or hypersensitivity at the eTNS stimulation site (maxillary branch of the trigeminal nerve).
- Current use of psychoactive medications or substances that may significantly alter EEG signals or brain state dynamics.
- Pregnant or lactating individuals.
- Poor sleep quality or irregular sleep-wake cycles prior to the experiment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xidian University
Xi'an, Shaanxi, 71000
Xue-Juan Yang, +8615691826100, xjyang@xidian.edu.cn
xjyang@xidian.edu.cn
About this study
Official title: A Study on the Enhancing Effects of 40 Hz Combined Trigeminal-Sensory Stimulation on Working Memory
The purpose of this study is to investigate the independent and interactive effects of 40Hz auditory, visual, and external trigeminal nerve stimulation (eTNS) on brain state dynamics and functional connectivity. While 40Hz visual and auditory sensory stimulation have been explored for potential cognitive and therapeutic benefits, the underlying mechanisms on large-scale brain networks and the potential effects of combining multiple modalities remain unclear.
This study aims to determine whether multimodal co-stimulation genuinely compounds network-level effects or if targeted dual-pairings are more efficient for brain network reorganization. In this within-subject study, 23 participants will receive all eight possible combinations of 40Hz auditory, visual, and eTNS (targeting the maxillary branch) in a randomized order. Each stimulation condition will last for 5 minutes, separated by 1-minute inter-stimulus intervals. Continuous electroencephalography (EEG) will be recorded throughout the procedures to evaluate brain responses. The collected EEG data will be analyzed using microstate analysis, functional connectivity analysis, and graph-theoretic network analysis. Ultimately, the study seeks to understand how these non-invasive stimulation techniques, independently and together, drive large-scale network reorganization and optimize the balance between local specialization and global integration in the brain.
Read the detailed description
Physical neuromodulation at 40 Hz has emerged as a promising therapeutic approach, with visual and auditory stimulation demonstrating the capacity to entrain gamma oscillations and confer cognitive benefits. Analogous effects have also been observed with electrical approaches, including external trigeminal nerve stimulation (eTNS). While the prevailing assumption in the field suggests that combining multiple sensory modalities will more comprehensively recruit distributed brain circuitry and yield greater therapeutic effects, the mechanistic foundations of this additive hypothesis remain contested. Furthermore, recent evidence indicates that network-level reorganization, rather than localized gamma entrainment, may represent a more causally relevant substrate for these cognitive improvements.
This study is designed to systematically characterize the independent and interactive effects of 40Hz auditory, visual, and eTNS stimulation on brain state dynamics, functional connectivity, and graph-theoretic network properties. The trial employs a fully crossed 2×2×2 within-subject design. A total of 23 participants will undergo all eight possible combinations of 40Hz stimulation modalities: sham (no stimulation), auditory only, visual only, eTNS only, auditory + visual, auditory + eTNS, visual + eTNS, and the three-way combination of auditory + visual + eTNS.
During the experimental session, the eTNS will specifically target the maxillary branch of the trigeminal nerve. The eight stimulation conditions will be administered in a randomized order for each participant. Each stimulation block will last for 5 minutes, separated by 1-minute inter-stimulus intervals to prevent carry-over effects.
Continuous electroencephalography (EEG) will be recorded throughout the session using a 32-channel eego™ mylab system (ANT Neuro, Netherlands) to capture real-time cortical responses. Following data acquisition, standard preprocessing pipelines will be applied, including notch filtering, 0.5-45Hz bandpass filtering, average re-referencing, ICA-based artifact rejection, and bad channel interpolation.
- Conditions
- Healthy Participants
- Being tested
- 40 Hz External Trigeminal Nerve Stimulation, 40 Hz Auditory Stimulation, 40 Hz Visual Stimulation, Sham Stimulation
- Keywords
- External trigeminal nerve stimulation (eTNS), 40Hz stimulation, Multimodal neuromodulation, Brain network reorganization, Network topology, Functional connectivity, EEG microstates
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
40 Hz External Trigeminal Nerve StimulationDevice
Electrical stimulation targeting the maxillary branch of the trigeminal nerve at a frequency of 40 Hz
40 Hz Auditory StimulationDevice
Auditory sensory stimulation delivered at 40 Hz for 5-minute durations
40 Hz Visual StimulationDevice
Visual sensory stimulation delivered at a frequency of 40 Hz for 5-minute durations
Sham StimulationOther
Inactive control stimulation designed to mimic the sensory experience of the active modalities without delivering actual 40 Hz therapeutic stimulation
| Study group | Role | What they receive |
|---|---|---|
| Experimental Crossover Group | Experimental | All participants are enrolled in this single crossover arm. Each participant will receive all eight combinations of 40Hz stimulation (auditory, visual, and external trigeminal nerve stimulation [eTNS] targeting the maxillary branch) in a randomized order, including a sham condition. Each stimulation condition lasts for 5 minutes, separated by 1-minute inter-stimulus intervals. Receives: Device: 40 Hz External Trigeminal Nerve Stimulation; Device: 40 Hz Auditory Stimulation; Device: 40 Hz Visual Stimulation; Other: Sham Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole-Brain Functional Connectivity (Phase-Locking Value)
Measured: Day1 (during the single experimental session)
Secondary outcomes (3)
EEG Microstate Dynamics (Mean Duration and Segment Density)
Brain state dynamics evaluated via microstate analysis of global field power (GFP) peaks. Primary metrics extracted include the mean duration and segment density (occurrence rate per minute) of identified microstate classes to assess modality-specific regulation.
Measured: Up to 1 hour (during the single experimental session)
EEG Phase-Locking Value (PLV)-Derived Global Efficiency
Continuous electroencephalography (EEG) data will be recorded. The specific parameter extracted from the EEG is the Phase-Locking Value (PLV) across theta (4-7Hz), alpha (8-12Hz), beta (13-30Hz), and gamma (31-45Hz) frequency bands. These PLV functional connectivity matrices will be used to construct weighted brain networks across a sparsity threshold range of 0.1 to 0.5. Global efficiency, a graph-theoretic metric representing network-wide communication integration, will then be calculated and reported based on these PLV networks.
Measured: Day1 (during the single experimental session)
EEG Phase-Locking Value (PLV)-Derived Small-World Propensity
Continuous electroencephalography (EEG) data will be recorded. The specific parameter extracted from the EEG is the Phase-Locking Value (PLV) across theta (4-7Hz), alpha (8-12Hz), beta (13-30Hz), and gamma (31-45Hz) frequency bands. These PLV functional connectivity matrices will be used to construct weighted brain networks across a sparsity threshold range of 0.1 to 0.5. Small-world propensity, a graph-theoretic metric evaluating the balance between local network specialization and global integration, will then be calculated and reported based on these PLV networks.
Measured: Day 1 (during the single experimental session)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2026
- Study start16 Jun 2026
- Primary completion22 Jun 2026
- Study completion23 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xidian University
- Sponsor type
- University, hospital or other
- Collaborators
- Xi'an Central Hospital
- Responsible party
- Sponsor
- Investigators
- Xue-Juan Yang, Principal investigator, Xidian University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07668167
- Sponsor's protocol ID
- 20260612
- Status last verified
- Jun 2026
- First submitted
- 12 Jun 2026
- Last updated
- 1 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD), particularly raw continuous electrophysiological recordings (EEG), contains sensitive and potentially identifiable biometric information. In accordance with institutional data security policies and ethical guidelines regarding participant privacy, raw IPD will not be made publicly available. However, aggregated statistical data and summary results will be published in peer-reviewed journals. De-identified, summary-level data or analytical scripts may be shared by the corresponding author upon reasonable academic request, subject to formal institutional review and approval.
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on the Enhancing Effects of 40 Hz Combined Trigeminal-Sensory Stimulation on Working Memory
- ClinicalTrials.gov ID
- NCT07668167
- Acronym / sponsor ID
- 20260612
- Conditions
- Healthy Participants
- Keywords
- External trigeminal nerve stimulation (eTNS), 40Hz stimulation, Multimodal neuromodulation, Brain network reorganization, Network topology, Functional connectivity, EEG microstates
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Xidian UniversityUniversity, hospital or other
- Collaborators
- Xi'an Central Hospital
- Study start
- 16 Jun 2026 (actual)
- Primary completion
- 22 Jun 2026 (actual)
- Study completion
- 23 Jun 2026 (estimated)
- First posted
- 25 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the independent and interactive effects of 40Hz auditory, visual, and external trigeminal nerve stimulation (eTNS) on brain state dynamics and functional connectivity. While 40Hz visual and auditory sensory stimulation have been explored for potential cognitive and therapeutic benefits, the underlying mechanisms on large-scale brain networks and the potential effects of combining multiple modalities remain unclear.
This study aims to determine whether multimodal co-stimulation genuinely compounds network-level effects or if targeted dual-pairings are more efficient for brain network reorganization. In this within-subject study, 23 participants will receive all eight possible combinations of 40Hz auditory, visual, and eTNS (targeting the maxillary branch) in a randomized order. Each stimulation condition will last for 5 minutes, separated by 1-minute inter-stimulus intervals. Continuous electroencephalography (EEG) will be recorded throughout the procedures to evaluate brain responses. The collected EEG data will be analyzed using microstate analysis, functional connectivity analysis, and graph-theoretic network analysis. Ultimately, the study seeks to understand how these non-invasive stimulation techniques, independently and together, drive large-scale network reorganization and optimize the balance between local specialization and global integration in the brain.
Detailed description
Physical neuromodulation at 40 Hz has emerged as a promising therapeutic approach, with visual and auditory stimulation demonstrating the capacity to entrain gamma oscillations and confer cognitive benefits. Analogous effects have also been observed with electrical approaches, including external trigeminal nerve stimulation (eTNS). While the prevailing assumption in the field suggests that combining multiple sensory modalities will more comprehensively recruit distributed brain circuitry and yield greater therapeutic effects, the mechanistic foundations of this additive hypothesis remain contested. Furthermore, recent evidence indicates that network-level reorganization, rather than localized gamma entrainment, may represent a more causally relevant substrate for these cognitive improvements.
This study is designed to systematically characterize the independent and interactive effects of 40Hz auditory, visual, and eTNS stimulation on brain state dynamics, functional connectivity, and graph-theoretic network properties. The trial employs a fully crossed 2×2×2 within-subject design. A total of 23 participants will undergo all eight possible combinations of 40Hz stimulation modalities: sham (no stimulation), auditory only, visual only, eTNS only, auditory + visual, auditory + eTNS, visual + eTNS, and the three-way combination of auditory + visual + eTNS.
During the experimental session, the eTNS will specifically target the maxillary branch of the trigeminal nerve. The eight stimulation conditions will be administered in a randomized order for each participant. Each stimulation block will last for 5 minutes, separated by 1-minute inter-stimulus intervals to prevent carry-over effects.
Continuous electroencephalography (EEG) will be recorded throughout the session using a 32-channel eego™ mylab system (ANT Neuro, Netherlands) to capture real-time cortical responses. Following data acquisition, standard preprocessing pipelines will be applied, including notch filtering, 0.5-45Hz bandpass filtering, average re-referencing, ICA-based artifact rejection, and bad channel interpolation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Crossover Group | Experimental | Device: 40 Hz External Trigeminal Nerve Stimulation, Device: 40 Hz Auditory Stimulation, Device: 40 Hz Visual Stimulation, Other: Sham StimulationAll participants are enrolled in this single crossover arm. Each participant will receive all eight combinations of 40Hz stimulation (auditory, visual, and external trigeminal nerve stimulation [eTNS] targeting the maxillary branch) in a randomized order, including a sham condition. Each stimulation condition lasts for 5 minutes, separated by 1-minute inter-stimulus intervals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy adults aged ≥18 years old.
- Normal or corrected-to-normal vision and hearing (essential for 40Hz visual and auditory stimulation).
- Right-handedness.
- Willing to participate in the study and capable of providing written informed consent.
Key exclusion criteria (7 listed)
- Personal or family history of epilepsy or seizures (crucial safety criteria for 40Hz flicker and electrical stimulation).
- History of any neurological or psychiatric disorders.
- Presence of metallic implants in the head, cardiac pacemakers, or other implanted electronic medical devices.
- Skin lesions, infections, or hypersensitivity at the eTNS stimulation site (maxillary branch of the trigeminal nerve).
- Current use of psychoactive medications or substances that may significantly alter EEG signals or brain state dynamics.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 40 Hz External Trigeminal Nerve StimulationElectrical stimulation targeting the maxillary branch of the trigeminal nerve at a frequency of 40 Hz | Device | Experimental Crossover Group |
| 40 Hz Auditory StimulationAuditory sensory stimulation delivered at 40 Hz for 5-minute durations | Device | Experimental Crossover Group |
| 40 Hz Visual StimulationVisual sensory stimulation delivered at a frequency of 40 Hz for 5-minute durations | Device | Experimental Crossover Group |
| Sham StimulationInactive control stimulation designed to mimic the sensory experience of the active modalities without delivering actual 40 Hz therapeutic stimulation | Other | Experimental Crossover Group |
Primary outcome
Whole-Brain Functional Connectivity (Phase-Locking Value)
Time frame: Day1 (during the single experimental session)
3 secondary outcomes
EEG Microstate Dynamics (Mean Duration and Segment Density)
Time frame: Up to 1 hour (during the single experimental session)
EEG Phase-Locking Value (PLV)-Derived Global Efficiency
Time frame: Day1 (during the single experimental session)
EEG Phase-Locking Value (PLV)-Derived Small-World Propensity
Time frame: Day 1 (during the single experimental session)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: No. Individual participant data (IPD), particularly raw continuous electrophysiological recordings (EEG), contains sensitive and potentially identifiable biometric information. In accordance with institutional data security policies and ethical guidelines regarding participant privacy, raw IPD will not be made publicly available. However, aggregated statistical data and summary results will be published in peer-reviewed journals. De-identified, summary-level data or analytical scripts may be shared by the corresponding author upon reasonable academic request, subject to formal institutional review and approval.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xue-Juan Yang principal investigator
Xidian University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 40 Hz External Trigeminal Nerve Stimulation, 40 Hz Auditory Stimulation and 40 Hz Visual Stimulation in people with Healthy Participants, run by Xidian University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xue-Juan Yang, Phd (86-029-81891070, xjyang@xidian.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole-Brain Functional Connectivity (Phase-Locking Value) (time frame: Day1 (during the single experimental session)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.