Physiology of Human Brain Connectivity
2 other identifiers
interventional
80
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable healthy
Started Dec 2024
Longer than P75 for not_applicable healthy
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 30, 2024
CompletedFirst Posted
Study publicly available on registry
February 7, 2024
CompletedStudy Start
First participant enrolled
December 13, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 15, 2027
November 10, 2025
November 1, 2025
2.3 years
January 30, 2024
November 7, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Secondary Outcomes (2)
Changes in resting-state EEG coherence
Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Changes in bimanual coordination task performance
Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS)
Study Arms (1)
Healthy Participants
EXPERIMENTALAll 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.
Interventions
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) 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).
Structural, diffusion, and functional MRI with a 3-Tesla Siemens scanner
Eligibility Criteria
You may qualify if:
- Age from 18 to 64 years
- Right-handed
- Normal hearing and (corrected) vision
- Able to understand and give informed consent
You may not qualify if:
- 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
- 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
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Massachusetts General Hospital
Boston, Massachusetts, 02129, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tommi Raij, MD, PhD
Massachusetts General Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Masking Details
- Participants will not be informed of the asynchrony value for each visit. The order of asynchronies is randomized.
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 30, 2024
First Posted
February 7, 2024
Study Start
December 13, 2024
Primary Completion (Estimated)
April 15, 2027
Study Completion (Estimated)
April 15, 2027
Last Updated
November 10, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- After publication
- Access Criteria
- Reasonable request
Anonymized EEG and MRI data