Modeling TMS-induced Cortical Network Activity

Mass General Brigham

Status: Not yet enrolling

Conditions: Healthy

Treatments: Device: Sessions 3 - 5: Paired associative stimulation (PAS); Device: Session 2: Single-pulse TMS (spTMS)

Study type: Interventional

Funder types: Other

Identifiers

NCT05288959

R01NS126337-01 (pending) (Other Grant/Funding Number)

R01NS126337-01 (U.S. NIH Grant/Contract)

2014p002652

Details and patient eligibility

About

This is a study of normal brain physiology in healthy human volunteers. The study aims to understand the physiology of connectivity between brain regions. To reach this aim, it delivers single-pulse transcranial magnetic stimulation (spTMS) to one or two brain areas at a time while electroencephalography (EEG) is measured. When only one brain area is stimulated (uni-focal TMS), the goal is to record how many milliseconds it takes for the activity to spread from the stimulated area to other brain regions (conduction delay). When two brain areas are stimulated (bi-focal TMS), the TMS pulses are separated by a short millisecond-level time interval ("asynchrony") in a so-called paired associative stimulation (PAS) design. The central hypothesis is that PAS may increase or decrease connectivity between the stimulated areas depending on the asynchrony value. All techniques in the study are non-invasive and considered safe.

Full description

The goal of the study is to illuminate the physiology of inter-regional connectivity in the human brain. Participants are healthy adult volunteers without disorders or medications influencing brain function (N=80). During uni-focal TMS, only one brain area is stimulated at a time, and the conduction delays and connectivity strengths between the stimulated brain area and other brain regions are quantified with source-resolved EEG. During the bi-focal TMS sessions, a range of negative and positive PAS asynchronies (from minus 50 to + 50 ms relative to the conduction delays) will be tested in separate sessions, and the within-session connectivity changes from PAS are estimated by applying uni-focal TMS before and after PAS. The targeted brain areas include the primary motor cortices in the left and right hemisphere as well as areas outside the primary motor cortices. All techniques included in the study are non-invasive and considered safe: TMS, EEG, electromyography (EMG), magnetic resonance imaging (MRI), diffusion MRI (dMRI), functional MRI (fMRI), and behavioral measures. The TMS parameters in this study are considered safe, as only single or pairs of TMS pulses are delivered.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy
• Normal hearing and (corrected) vision
• Able to understand and give informed consent

Exclusion criteria

• Metal in the body (rods, plates, screws, shrapnel, dentures, IUD)
• Metallic particles in the eye
• Surgical clips in the head or previous neurosurgery
• Cardiac pacemaker or pacemaker wires
• Neurostimulators
• Implanted pumps
• Any magnetic particles in the body
• Cochlear implants
• Prosthetic heart valves
• Epilepsy or any other type of seizure history
• Significant claustrophobia
• Meniere's disease
• Pregnancy or breast-feeding
• Diagnoses or medications (neurological or psychiatric) influencing brain function
• History of, or current, substance abuse
• History of developmental disorders (e.g., dyslexia)
• Failure to perform the behavioral tasks
• Prisoners

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

Healthy participants

Experimental group

Description:

All participants participate in five core sessions. Session 1 consists of MRI scans (T1-weighted, T2-weighted, diffusion MRI, resting-state fMRI). Thereafter, there are four TMS-EEG sessions. Session 2 delivers uni-focal spTMS to various cortical targets while EEG is recorded to determine inter-regional conduction delays. Thereafter, Sessions 3 - 5 deliver bi-focal TMS (PAS), each session using a different asynchrony (shorter, equal to, or longer than the conduction delay). The three PAS sessions are at least one week apart. Each of the PAS sessions have three segments: (a) TMS-EEG-behavioral recordings before PAS, (b) the PAS modulation, and (c) TMS-EEG-behavioral recordings after PAS. In addition to these core sessions, some participants may be invited for additional sessions for parameter optimization and for assessing test-retest repeatability.

Treatment:

Device: Session 2: Single-pulse TMS (spTMS)

Device: Sessions 3 - 5: Paired associative stimulation (PAS)