NCT06246942

Physiology of Human Brain Connectivity

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Accepted

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.

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

Interventions

Type	Name	Description
DEVICE	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	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).
DIAGNOSTIC_TEST	Magnetic resonance imaging (MRI)	Structural, diffusion, and functional MRI with a 3-Tesla Siemens scanner

Timeline

• Start date: 2024-12-13
• Primary completion: 2027-04-15
• Completion: 2027-04-15
• First posted: 2024-02-07
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States