HealthyNCT06246942
Physiology of Human Brain Connectivity
A study testing Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS) and Magnetic resonance imaging (MRI) in people with Healthy, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to investigate the effective connectivity between different regions of the human brain in healthy participants, and the mechanisms which influence and modulate its development. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS) and Magnetic resonance imaging (MRI)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2024to 15 Apr 2027
- 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 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age from 18 to 64 years
- Right-handed
- Normal hearing and (corrected) vision
- Able to understand and give informed consent
Who cannot join
- Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
- Metal in the body (e.g., rods, plates, screws, shrapnel, dentures that cannot be removed during the recordings, IUD)
- Suspected metallic particles in the eye
- Surgical clips in the head or previous neurosurgery
- Any magnetic particles in the body
- Cochlear implants
Show all 17Show fewer
- Prosthetic heart valves
- Epilepsy or any other type of seizure history
- Any neurological diagnoses or medications influencing brain function
- History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae)
- Known structural brain lesion
- Significant other disease (heart disease, malignant tumors, mental disorders)
- Significant claustrophobia; Ménière's disease
- Pregnancy (ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible), breast feeding
- Non prescribed drug use
- Failure to perform the behavioral tasks or neuropsychological evaluation tests
- Prisoners
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
Massachusetts General Hospital
Boston, Massachusetts, 02129
About this study
The purpose of this study is to investigate the effective connectivity between different regions of the human brain in healthy participants, and the mechanisms which influence and modulate its development. Specifically, the investigators will examine the effects of cortico-cortical paired associative stimulation (ccPAS) which is induced by the application of brief (< 1 ms) transcranial magnetic stimulation (TMS) pulses separated by a short millisecond-level time intervals ("asynchrony") to two different areas of the brain. All techniques are non-invasive and considered safe in humans: TMS, electroencephalography (EEG), and magnetic resonance imaging (MRI). Based on previous animal and human studies, it is hypothesized that ccPAS will increase or decrease effective connectivity between the stimulated areas depending on the asynchrony value. The main outcome measure is source-resolved EEG cortico-cortical evoked potentials (ccEPs) elicited by single-pulse TMS.
Read the detailed description
The purpose of this study is to determine the extent to which effective connectivity between different regions in the human brain can be selectively modulated by cortico-cortical paired associative stimulation (ccPAS) induced by transcranial magnetic stimulation (TMS). Study subjects will consist of healthy adults between the ages of 18 and 64 (N=80) . Participants will have TMS pulses applied to two brain regions, one in each hemisphere, where the two regions will be stimulated at a range of different temporal offsets ("asynchronies") characterized as being either shorter, longer, or approximately equal to the theorized inter-regional conduction delays, with absolute disparities between the asynchrony conditions on the order of milliseconds. Additionally, electroencephalography (EEG) will be concurrently measured to record cortico-cortical evoked potentials (ccEPs), which are the study's primary outcome measure. Asynchronies longer than the delay are hypothesized to increase effective connectivity and ccEP amplitudes, while shorter delays are expected to decrease them. This will be further supported by magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion MRI (dMRI) scans to provide structural and functional data to assist with ccPAS application.
The initial study visit will consist of the MRI scans followed by a TMS session to record participant motor thresholds. The ccPAS TMS-EEG procedures will then be performed over the course of three additional visits, with each asynchrony condition conducted on its own separate visit and at least a week between them. Prior to ccPAS application, single-pulse TMS will be applied to one brain area to record ccEPs, in addition to resting-state EEG and a behavioral motor test. These will be repeated two additional times, once 5 minutes after ccPAS and again at 60 minutes after, to observe effect duration. All techniques and devices are non-invasive and considered safe within the parameters of the study, with overall participation carrying only non-significant risk.
- Conditions
- Healthy
- Being tested
- Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS), Magnetic resonance imaging (MRI)
- Keywords
- Paired Associative Stimulation, Transcranial Magnetic Stimulation, Electroencephalography, Effective Connectivity, Human Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single-pulse transcranial magnetic stimulation (spTMS)Device
Single-pulse TMS (spTMS) will be delivered with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 80 spTMS will be repeated at 0.2 Hz. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, Bonn, Germany).
Paired associative stimulation (PAS)Device
Paired associative stimulation (PAS) will be applied with two TMS stimulators (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and two TMS coils. The pulses from each stimulator/coil will be repeated at 0.2 Hz, duration of run 15 minutes (180 pulses for each stimulator/coil). In different sessions, we will deliver PAS with different asynchrony values to examine their effects on effective connectivity. Coils will be navigated using an MRI-based TMS navigation system (Localite, Bonn, Germany).
Magnetic resonance imaging (MRI)Diagnostic test
Structural, diffusion, and functional MRI with a 3-Tesla Siemens scanner
| Study group | Role | What they receive |
|---|---|---|
| Healthy Participants | Experimental | All participants will be scheduled for a minimum of four separate visits. The first visit will consist of MRI scanning sessions (including T1 and T2 structural MRI, diffusion MRI, and resting-state fMRI), followed by a single-pulse TMS session to determine the participant's resting motor threshold. The remaining three visits consist of a series of TMS-EEG runs using the paired associative stimulation (PAS) methodology. Each visit will be restricted to a single asynchrony condition with every participant receiving all three conditions over the course of the three visits. Participants will not be informed of which asynchrony condition they are receiving on any given visit.
Some subjects may be invited for additional sessions for the purposes of optimizing TMS, EEG, or MRI parameters, and to assess test-retest reliability. Receives: Device: Single-pulse transcranial magnetic stimulation (spTMS); Device: Paired associative stimulation (PAS); Diagnostic Test: Magnetic resonance imaging (MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in EEG effective connectivity
EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne 64, Bittium, Kuopio, Finland). Data will be collected before (Pre) and at 5 minutes (Post-1) and at 60 minutes (Post-2) after PAS. To record spTMS-evoked EEG responses the investigators will deliver 80 single TMS pulses to the two areas receiving PAS, one target after the other in separate runs. Effective connectivity will be measured by comparing the source-resolved EEG evoked response waveforms before (Pre) and at 5 (Post-1) and at 60 minutes after PAS (Post-2).
Measured: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Secondary outcomes (2)
Changes in resting-state EEG coherence
Resting-state EEG will be recorded with a 64-channel whole-head device (NeurOne 64, Bittium, Kuopio, Finland). Data will be collected before (Pre) and at 5 minutes (Post-1) and at 60 minutes (Post-2) after PAS. Resting-state EEG coherence will be computed in the source space for the two areas receiving PAS.
Measured: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Changes in bimanual coordination task performance
Participants will engage in a simple bimanual coordination task before (Pre), 5 minutes following (Post-1), and 60 minutes following (Post-2) PAS application for the purpose of providing behavioral data on inter-hemisphere connections between the motor cortices. The measure will be quantified by comparisons between participant task performance pre- and post- PAS application.
Measured: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2024
- Study start13 Dec 2024
- Primary completion15 Apr 2027 (estimated)
- Study completion15 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Model description
- PAS will be applied to two cortical targets at a minimum of 3 different asynchronies to modulate connectivity. PAS may selectively increase or decrease effective connectivity depending on the asynchrony. Negative asynchronies are expected to decrease effective connectivity, whereas positive asynchronies to increase it. All participants will be stimulated with all 3 asynchronies (on different visits).
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tommi A. Raij, Massachusetts General Hospital
- Investigators
- Tommi Raij, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06246942
- Sponsor's protocol ID
- 2024p000098
- Other IDs
- 5R01NS126337
- Status last verified
- Nov 2025
- First submitted
- 30 Jan 2024
- Last updated
- 10 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized EEG and MRI data
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiology of Human Brain Connectivity
- ClinicalTrials.gov ID
- NCT06246942
- Acronym / sponsor ID
- 2024p000098
- Conditions
- Healthy
- Keywords
- Paired Associative Stimulation, Transcranial Magnetic Stimulation, Electroencephalography, Effective Connectivity, Human Brain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 13 Dec 2024 (actual)
- Primary completion
- 15 Apr 2027 (estimated)
- Study completion
- 15 Apr 2027 (estimated)
- First posted
- 7 Feb 2024 (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 effective connectivity between different regions of the human brain in healthy participants, and the mechanisms which influence and modulate its development. Specifically, the investigators will examine the effects of cortico-cortical paired associative stimulation (ccPAS) which is induced by the application of brief (< 1 ms) transcranial magnetic stimulation (TMS) pulses separated by a short millisecond-level time intervals ("asynchrony") to two different areas of the brain. All techniques are non-invasive and considered safe in humans: TMS, electroencephalography (EEG), and magnetic resonance imaging (MRI). Based on previous animal and human studies, it is hypothesized that ccPAS will increase or decrease effective connectivity between the stimulated areas depending on the asynchrony value. The main outcome measure is source-resolved EEG cortico-cortical evoked potentials (ccEPs) elicited by single-pulse TMS.
Detailed description
The purpose of this study is to determine the extent to which effective connectivity between different regions in the human brain can be selectively modulated by cortico-cortical paired associative stimulation (ccPAS) induced by transcranial magnetic stimulation (TMS). Study subjects will consist of healthy adults between the ages of 18 and 64 (N=80) . Participants will have TMS pulses applied to two brain regions, one in each hemisphere, where the two regions will be stimulated at a range of different temporal offsets ("asynchronies") characterized as being either shorter, longer, or approximately equal to the theorized inter-regional conduction delays, with absolute disparities between the asynchrony conditions on the order of milliseconds. Additionally, electroencephalography (EEG) will be concurrently measured to record cortico-cortical evoked potentials (ccEPs), which are the study's primary outcome measure. Asynchronies longer than the delay are hypothesized to increase effective connectivity and ccEP amplitudes, while shorter delays are expected to decrease them. This will be further supported by magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion MRI (dMRI) scans to provide structural and functional data to assist with ccPAS application.
The initial study visit will consist of the MRI scans followed by a TMS session to record participant motor thresholds. The ccPAS TMS-EEG procedures will then be performed over the course of three additional visits, with each asynchrony condition conducted on its own separate visit and at least a week between them. Prior to ccPAS application, single-pulse TMS will be applied to one brain area to record ccEPs, in addition to resting-state EEG and a behavioral motor test. These will be repeated two additional times, once 5 minutes after ccPAS and again at 60 minutes after, to observe effect duration. All techniques and devices are non-invasive and considered safe within the parameters of the study, with overall participation carrying only non-significant risk.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- PAS will be applied to two cortical targets at a minimum of 3 different asynchronies to modulate connectivity. PAS may selectively increase or decrease effective connectivity depending on the asynchrony. Negative asynchronies are expected to decrease effective connectivity, whereas positive asynchronies to increase it. All participants will be stimulated with all 3 asynchronies (on different visits).
| Arm | Type | Receives |
|---|---|---|
| Healthy Participants | Experimental | Device: Single-pulse transcranial magnetic stimulation (spTMS), Device: Paired associative stimulation (PAS), Diagnostic Test: Magnetic resonance imaging (MRI)All participants will be scheduled for a minimum of four separate visits. The first visit will consist of MRI scanning sessions (including T1 and T2 structural MRI, diffusion MRI, and resting-state fMRI), followed by a single-pulse TMS session to determine the participant's resting motor threshold. The remaining three visits consist of a series of TMS-EEG runs using the paired associative stimulation (PAS) methodology. Each visit will be restricted to a single asynchrony condition with every participant receiving all three conditions over the course of the three visits. Participants will not be informed of which asynchrony condition they are receiving on any given visit. Some subjects may be invited for additional sessions for the purposes of optimizing TMS, EEG, or MRI parameters, and to assess test-retest reliability. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age from 18 to 64 years
- Right-handed
- Normal hearing and (corrected) vision
- Able to understand and give informed consent
Key exclusion criteria (17 listed)
- Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
- Metal in the body (e.g., rods, plates, screws, shrapnel, dentures that cannot be removed during the recordings, IUD)
- Suspected metallic particles in the eye
- Surgical clips in the head or previous neurosurgery
- Any magnetic particles in the body
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 |
|---|---|---|
| Single-pulse transcranial magnetic stimulation (spTMS)Single-pulse TMS (spTMS) will be delivered with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 80 spTMS will be repeated at 0.2 Hz. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, Bonn, Germany). | Device | Healthy Participants |
| Paired associative stimulation (PAS)Paired associative stimulation (PAS) will be applied with two TMS stimulators (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and two TMS coils. The pulses from each stimulator/coil will be repeated at 0.2 Hz, duration of run 15 minutes (180 pulses for each stimulator/coil). In different sessions, we will deliver PAS with different asynchrony values to examine their effects on effective connectivity. Coils will be navigated using an MRI-based TMS navigation system (Localite, Bonn, Germany). | Device | Healthy Participants |
| Magnetic resonance imaging (MRI)Structural, diffusion, and functional MRI with a 3-Tesla Siemens scanner | Diagnostic test | Healthy Participants |
Primary outcome
Changes in EEG effective connectivity
Time frame: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne 64, Bittium, Kuopio, Finland). Data will be collected before (Pre) and at 5 minutes (Post-1) and at 60 minutes (Post-2) after PAS. To record spTMS-evoked EEG responses the investigators will deliver 80 single TMS pulses to the two areas receiving PAS, one target after the other in separate runs. Effective connectivity will be measured by comparing the source-resolved EEG evoked response waveforms before (Pre) and at 5 (Post-1) and at 60 minutes after PAS (Post-2).
2 secondary outcomes
Changes in resting-state EEG coherence
Time frame: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Changes in bimanual coordination task performance
Time frame: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
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 10 Nov 2025.
- Individual participant dataSharing planned: Yes. Anonymized EEG and MRI data
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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.
Tommi Raij, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single-pulse transcranial magnetic stimulation (spTMS), Paired associative stimulation (PAS) and Magnetic resonance imaging (MRI) in people with Healthy, run by Massachusetts General Hospital 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 4 inclusion and 17 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 10 Nov 2025. 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. 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 Netri Pajankar, MS (617-726-2000, npajankar@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in EEG effective connectivity (time frame: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)). 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 10 Nov 2025.