Recruiting

ccPAS

Sponsor:

Massachusetts General Hospital

Code:

NCT06246942

Conditions

Healthy

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Accepted

Interventions

Single-pulse transcranial magnetic stimulation (spTMS)

Paired associative stimulation (PAS)

Magnetic resonance imaging (MRI)

Study Details

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.

Conditions

Healthy

Study ID

NCT06246942

Start date

Dec 13, 2024

Status verified date

Nov, 2025

Completion date

Apr 15, 2027

Anticipated

Primary completion date

Apr 15, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 64

Healthy Volunteers: Accepted

Inclusion Criteria:

  • Age from 18 to 64 years
  • Right-handed
  • Normal hearing and (corrected) vision
  • Able to understand and give informed consent

Exclusion Criteria:

  • 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
  • Failure to perform the behavioral tasks or neuropsychological evaluation tests
  • Prisoners

Study Design

Enrollment

80 participants

Anticipated

Intervention Model

Single group

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Healthy Participants

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.

Interventions

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).

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).

Magnetic resonance imaging (MRI)

Structural, diffusion, and functional MRI with a 3-Tesla Siemens scanner

Primary outcome measure

  • Changes in EEG effective connectivity [ Time Frame: Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS) ]

Central Contacts and Locations

Central contacts

Netri Pajankar, MS

617-726-2000npajankar@mgh.harvard.edu

Gabriel Fadel, MS

617-726-2000gfadel@mgh.harvard.edu

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02129

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Nov 10, 2025

Last verified

Nov, 2025

Keywords

  • Paired Associative Stimulation
  • Transcranial Magnetic Stimulation
  • Electroencephalography
  • Effective Connectivity
  • Human Brain

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2025-11-10.