Healthy Adult ParticipantsNCT07593859
Overcoming the Barriers to Effective Transcranial Temporal Interference Stimulation in Humans
A study testing transcranial Temporal Interference Stimulation in people with Healthy Adult Participants, run by Northeastern University at 1 site in United States.
Trial summary
Transcranial temporal interference stimulation (TIS) is an emerging novel tool for non-invasive transcranial brain stimulation that holds the potential for focal and steerable neuromodulation, and the possibility to stimulate focally at depth. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Participants
- What is being tested?
- transcranial Temporal Interference 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 siteUnited States
- Study dates
- 1 Feb 2026to 1 Oct 2029
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Free of neurological or orthopedic conditions that may impact the ability to participate.
- Right-hand dominant (self-reported)
- Aged 18-65 years
Who cannot join
- Ferromagnetic metal implants in the brain/skull or elsewhere (dental implants excluded).
- Any implanted electronic device (e.g. cardiac pacemaker, cochlear implant, deep brain stimulator, medication infusion pump; vagal nerve stimulator)
- Diseased or damaged skin on face or scalp
- History of migraines, fainting, seizures/epilepsy, or psychiatric illness
- Neurological disorder or intracranial lesion
- Frequent or severe headaches
Show all 13Show fewer
- Prior adverse reaction to transcranial magnetic stimulation
- Currently pregnant
- Suspected or diagnosed heart problems (e.g. arrhythmia, cardiac disturbances).
- Insulin-dependent diabetes
- Suspected or diagnosed epilepsy or a familial history of epilepsy
- Use of alcohol or recreational drugs in the prior 12 hours
- Use of prescription and over the counter medications will be grounds for exclusion except for: contraceptive (birth control) drugs (e.g. those containing ethinyl estradiol and/or norethindrone), and seasonal allergy medications (e.g. cetirizine (Zyrtec), fexofenadine (Allegra), and loratadine (Claritin)).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Northeastern University
Boston, Massachusetts, 02115-5724
Mathew Yarossi, PhD, 7027828483, m.yarossi@northeastern.edu
Mathew Yarossi, PhD
About this study
Transcranial temporal interference stimulation (TIS) is an emerging novel tool for non-invasive transcranial brain stimulation that holds the potential for focal and steerable neuromodulation, and the possibility to stimulate focally at depth. TIS involves combining two high frequency waveforms to create a waveform with a "beat" frequency that is physiological relevant for neuromodulation. Successful applications to deep brain targets as well as steerability of the stimulation focus have been demonstrated in mice. Numerous recent investigations in humans have shown great clinical potential for this technology, however several questions about the basic mechanism of TIS action remain. The investigators will apply TIS to the motor cortex of humans and use established transcranial magnetic stimulation techniques to assess cortical excitability in relation to the phase of the TIS waveform. Using TMS, the investigators will i) validate that effects of TIS are due to the "beat" frequency and not the high frequency carrier signal, ii) evaluate the effect of the TIS carrier frequency, and iii) evaluate that whether changes in corticospinal excitability outlast the period of stimulation. Knowledge gained from this experiment will provide a basis for the future use of TIS for clinical applications, including informing parameter optimization.
Read the detailed description
Remedies for treatment resistance in psychiatric and neurological disorders is a great unmet need. Invasive neuromodulation, such as deep brain stimulation (DBS), applied to a targeted brain region is one option that has helped regulate or modify, abnormal electrical patterns in many patients with neurological deficits; However, invasive approaches carry significant risks while having limited targeting flexibility. Transcranial temporal interference stimulation (TIS) is a non-invasive neuromodulation method with much more favorable focus in deep brain targets than traditional forms of transcranial alternating current stimulation (tACS). tTIS achieves its focal effect by delivering two sinusoidal currents, that are both high in frequency, but that are slightly different from one another (e.g. 1000 kHz and 1020 kHz) through electrodes placed on the scalp. Frequencies that are in the kilohertz range alone do not elicit neuronal response, however the interaction of the two high-frequency currents creates an electric field with a high-frequency carrier (fc, e.g. 1010 kHZ) that is modulated by a low-frequency beat (fb, e.g. 20 Hz). If fc is high enough (>1 kHz) and fb low enough (<100 Hz), neurons respond much more strongly to fb than fc.
Safety and tolerability of TIS has recently been demonstrated in humans with findings indicating that TIS poses no greater risk than other common non-invasive techniques for transcranial current stimulation (TCS). The spatial distribution of the beat field (Eb) is distinct from other noninvasive stimulation methods in three ways: 1) it is focal, 2) it can peak deep in the brain, 3) it can be steered through the brain without moving the electrodes. These features have been demonstrated in mouse experiments, and in human simulation studies.
In humans, motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) applied to the motor cortex provide an established assay of corticospinal excitability. TMS experiments have provided direct evidence that phase-dependent neuromodulation can be induced by transcranial alternating current stimulation (tACS), a form of transcranial current stimulation that is similar to temporal interference stimulation (TIS) but lacks focality and steerability, yet has been key to understanding its neurophysiological effects in humans. For example, recent experimental results showed that TMS pulses time locked to tACS over motor cortex induced MEP amplitude modulation that was dependent on the phase of the tACS oscillatory currents. Building on this finding, the investigators will provide TMS pulses to motor cortex during tTIS and investigate whether neuromodulation of corticospinal excitability depends on the phase of beat frequency (fb). Similar to the experiments that showed neural activation in mice, the investigators will also investigate whether the strength of the effect depends on the carrier frequency (fc). The investigators will use computationally optimized electrode placement, with high- and low-frequency controls, to test that effects are unambiguously due to fb. Finally, the investigators will assess corticospinal excitability PRE and POST stimulation to investigate neuroplasticity induced by TIS. The knowledge gained in this experiment will demonstrate the extent to which modulation effects of TIS in humans are due entrainment of neural activity at fb. This information will provide a basis for the future use of tTIS for clinical applications.
- Conditions
- Healthy Adult Participants
- Being tested
- transcranial Temporal Interference Stimulation
- Keywords
- transcranial temporal interference stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial Temporal Interference StimulationDevice
We will apply temporal interference stimulation (tTIS) for 20 minutes over the motor cortex concurrent with single-pulse transcranial magnetic stimulation (TMS) (also over the motor cortex). Motor evoked potentials will be recorded using electromyography (EMG).
| Study group | Role | What they receive |
|---|---|---|
| 990-1010 Hz fb | Experimental | 990-1010 Hz fb Receives: Device: transcranial Temporal Interference Stimulation |
| 1990-2010 Hz fb | Experimental | 1990-2010 Hz fb Receives: Device: transcranial Temporal Interference Stimulation |
| 1000-1000 Hz fb | Experimental | 1000-1000 Hz fb Receives: Device: transcranial Temporal Interference Stimulation |
| 2000-2000 Hz fb | Experimental | 2000-2000 Hz fb Receives: Device: transcranial Temporal Interference Stimulation |
| 20 Hz | Experimental | 20 Hz Receives: Device: transcranial Temporal Interference Stimulation |
| sham | Sham comparator | sham Receives: Device: transcranial Temporal Interference Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Online phase-dependent modulation of corticospinal excitability using the relevance value (R.V.)
Explained variance (R2) of best-fit sinusoids will be multiplied by the variance of measured values to obtain the established "relevance value" (R.V.), to be used as our primary outcome. Relevance values assume phase-dependent modulation with a large amplitude is more meaningful than one with small amplitude and the same R2. Critically, phase-dependent responses to TIS represent direct evidence of modulation at beat frequency (fb).
Measured: Periprocedural
Secondary outcomes (2)
Offline neuroplastic effects from pre to post
We define neuro- plastic effects as sustained modulation of excitability fol- lowing cessation of transcranial current sitmulation (tCS). Fifteen single-pulse MEPs will be acquired at the FDI hotspot prior to and at 0, 15 and 30 minutes after tCS (tpre, t0, t15, t30). Our primary outcome will be MEP amplitude change from tpre to t0.
Measured: Periprocedural
Offline neuroplastic post effects
Retention of neuromodulation at t15 and t30.
Measured: Periprocedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2026
- Study start1 Feb 2026
- Primary completion1 Oct 2029 (estimated)
- Study completion1 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Adult 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
- Randomised
- Intervention model
- Crossover
- Model description
- Healthy, right-handed adults (18-65 yo) will participate following institutionally approved informed consent. Participants will be free of neurological diagnoses, head trauma resulting in loss of consciousness, psychiatric or cognitive conditions, and will meet tCS and TMS safety requirements. Throughout all experiments participants will sit comfortably, arms supported at their sides, feet on a foot rest, viewing a dot on the wall facing them. The experiment is a double-blind randomized cross-over study that will include 23-30 individuals. All study conditions will be evaluated in separate sessions, which will be counterbalanced across participants and spaced 48-96 hrs apart to prevent carry-over effects. We will test for phase-dependent and neuroplastic effects of TIS in a controlled study with 6 conditions.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northeastern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Mathew Yarossi, Northeastern University
- Investigators
- Mathew Yarossi, PhD, Principal investigator, Northeastern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07593859
- Sponsor's protocol ID
- 25-02-54
- Other IDs
- 5R01NS133229
- Status last verified
- May 2026
- First submitted
- 5 May 2026
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Overcoming the Barriers to Effective Transcranial Temporal Interference Stimulation in Humans
- ClinicalTrials.gov ID
- NCT07593859
- Acronym / sponsor ID
- 25-02-54
- Conditions
- Healthy Adult Participants
- Keywords
- transcranial temporal interference stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Northeastern UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Feb 2026 (actual)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 1 Oct 2029 (estimated)
- First posted
- 18 May 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.
Transcranial temporal interference stimulation (TIS) is an emerging novel tool for non-invasive transcranial brain stimulation that holds the potential for focal and steerable neuromodulation, and the possibility to stimulate focally at depth. TIS involves combining two high frequency waveforms to create a waveform with a "beat" frequency that is physiological relevant for neuromodulation. Successful applications to deep brain targets as well as steerability of the stimulation focus have been demonstrated in mice. Numerous recent investigations in humans have shown great clinical potential for this technology, however several questions about the basic mechanism of TIS action remain. The investigators will apply TIS to the motor cortex of humans and use established transcranial magnetic stimulation techniques to assess cortical excitability in relation to the phase of the TIS waveform. Using TMS, the investigators will i) validate that effects of TIS are due to the "beat" frequency and not the high frequency carrier signal, ii) evaluate the effect of the TIS carrier frequency, and iii) evaluate that whether changes in corticospinal excitability outlast the period of stimulation. Knowledge gained from this experiment will provide a basis for the future use of TIS for clinical applications, including informing parameter optimization.
Detailed description
Remedies for treatment resistance in psychiatric and neurological disorders is a great unmet need. Invasive neuromodulation, such as deep brain stimulation (DBS), applied to a targeted brain region is one option that has helped regulate or modify, abnormal electrical patterns in many patients with neurological deficits; However, invasive approaches carry significant risks while having limited targeting flexibility. Transcranial temporal interference stimulation (TIS) is a non-invasive neuromodulation method with much more favorable focus in deep brain targets than traditional forms of transcranial alternating current stimulation (tACS). tTIS achieves its focal effect by delivering two sinusoidal currents, that are both high in frequency, but that are slightly different from one another (e.g. 1000 kHz and 1020 kHz) through electrodes placed on the scalp. Frequencies that are in the kilohertz range alone do not elicit neuronal response, however the interaction of the two high-frequency currents creates an electric field with a high-frequency carrier (fc, e.g. 1010 kHZ) that is modulated by a low-frequency beat (fb, e.g. 20 Hz). If fc is high enough (>1 kHz) and fb low enough (<100 Hz), neurons respond much more strongly to fb than fc.
Safety and tolerability of TIS has recently been demonstrated in humans with findings indicating that TIS poses no greater risk than other common non-invasive techniques for transcranial current stimulation (TCS). The spatial distribution of the beat field (Eb) is distinct from other noninvasive stimulation methods in three ways: 1) it is focal, 2) it can peak deep in the brain, 3) it can be steered through the brain without moving the electrodes. These features have been demonstrated in mouse experiments, and in human simulation studies.
In humans, motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) applied to the motor cortex provide an established assay of corticospinal excitability. TMS experiments have provided direct evidence that phase-dependent neuromodulation can be induced by transcranial alternating current stimulation (tACS), a form of transcranial current stimulation that is similar to temporal interference stimulation (TIS) but lacks focality and steerability, yet has been key to understanding its neurophysiological effects in humans. For example, recent experimental results showed that TMS pulses time locked to tACS over motor cortex induced MEP amplitude modulation that was dependent on the phase of the tACS oscillatory currents. Building on this finding, the investigators will provide TMS pulses to motor cortex during tTIS and investigate whether neuromodulation of corticospinal excitability depends on the phase of beat frequency (fb). Similar to the experiments that showed neural activation in mice, the investigators will also investigate whether the strength of the effect depends on the carrier frequency (fc). The investigators will use computationally optimized electrode placement, with high- and low-frequency controls, to test that effects are unambiguously due to fb. Finally, the investigators will assess corticospinal excitability PRE and POST stimulation to investigate neuroplasticity induced by TIS. The knowledge gained in this experiment will demonstrate the extent to which modulation effects of TIS in humans are due entrainment of neural activity at fb. This information will provide a basis for the future use of tTIS for clinical applications.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
- Model description
- Healthy, right-handed adults (18-65 yo) will participate following institutionally approved informed consent. Participants will be free of neurological diagnoses, head trauma resulting in loss of consciousness, psychiatric or cognitive conditions, and will meet tCS and TMS safety requirements. Throughout all experiments participants will sit comfortably, arms supported at their sides, feet on a foot rest, viewing a dot on the wall facing them. The experiment is a double-blind randomized cross-over study that will include 23-30 individuals. All study conditions will be evaluated in separate sessions, which will be counterbalanced across participants and spaced 48-96 hrs apart to prevent carry-over effects. We will test for phase-dependent and neuroplastic effects of TIS in a controlled study with 6 conditions.
| Arm | Type | Receives |
|---|---|---|
| 990-1010 Hz fb | Experimental | Device: transcranial Temporal Interference Stimulation990-1010 Hz fb |
| 1990-2010 Hz fb | Experimental | Device: transcranial Temporal Interference Stimulation1990-2010 Hz fb |
| 1000-1000 Hz fb | Experimental | Device: transcranial Temporal Interference Stimulation1000-1000 Hz fb |
| 2000-2000 Hz fb | Experimental | Device: transcranial Temporal Interference Stimulation2000-2000 Hz fb |
| 20 Hz | Experimental | Device: transcranial Temporal Interference Stimulation20 Hz |
| sham | Sham comparator | Device: transcranial Temporal Interference Stimulationsham |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Free of neurological or orthopedic conditions that may impact the ability to participate.
- Right-hand dominant (self-reported)
- Aged 18-65 years
Key exclusion criteria (13 listed)
- Ferromagnetic metal implants in the brain/skull or elsewhere (dental implants excluded).
- Any implanted electronic device (e.g. cardiac pacemaker, cochlear implant, deep brain stimulator, medication infusion pump; vagal nerve stimulator)
- Diseased or damaged skin on face or scalp
- History of migraines, fainting, seizures/epilepsy, or psychiatric illness
- Neurological disorder or intracranial lesion
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 |
|---|---|---|
| transcranial Temporal Interference StimulationWe will apply temporal interference stimulation (tTIS) for 20 minutes over the motor cortex concurrent with single-pulse transcranial magnetic stimulation (TMS) (also over the motor cortex). Motor evoked potentials will be recorded using electromyography (EMG). | Device | 1000-1000 Hz fb, 1990-2010 Hz fb, 20 Hz, 2000-2000 Hz fb, 990-1010 Hz fb, sham |
Primary outcome
Online phase-dependent modulation of corticospinal excitability using the relevance value (R.V.)
Time frame: Periprocedural
Explained variance (R2) of best-fit sinusoids will be multiplied by the variance of measured values to obtain the established "relevance value" (R.V.), to be used as our primary outcome. Relevance values assume phase-dependent modulation with a large amplitude is more meaningful than one with small amplitude and the same R2. Critically, phase-dependent responses to TIS represent direct evidence of modulation at beat frequency (fb).
2 secondary outcomes
Offline neuroplastic effects from pre to post
Time frame: Periprocedural
Offline neuroplastic post effects
Time frame: Periprocedural
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 18 May 2026.
- Individual participant dataSharing planned: Undecided
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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.
Mathew Yarossi, PhD principal investigator
Northeastern 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 transcranial Temporal Interference Stimulation in people with Healthy Adult Participants, run by Northeastern University at 1 site in United States.
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 3 inclusion and 13 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 18 May 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 United States. 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. Some participants in this study may receive a placebo. 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 Joanne Hall, M.Sc. (17027828483, hall.joa@northeastern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Online phase-dependent modulation of corticospinal excitability using the relevance value (R.V.) (time frame: Periprocedural). 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 18 May 2026; AzTrials last refreshed its copy on 31 Oct 2026.