Modeling TMS-induced Cortical Network Activity

NCT ID: NCT05288959

Last Updated: 2022-03-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2027-03-31

Brief Summary

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.

Detailed 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.

Conditions

Healthy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy participants

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.

Group Type: EXPERIMENTAL

Session 2: Single-pulse TMS (spTMS)

Intervention Type: DEVICE

Uni-focal TMS (MagVenture, Farum, Denmark) is delivered to one brain area while EEG/EMG (NeurOne, Bittium, Kuopio, Finland) are recorded. The targeted brain areas and TMS intensities may vary across runs. An MRI-based TMS navigation system (Localite, Bonn, Germany) is used to navigate the TMS coil.

Sessions 3 - 5: Paired associative stimulation (PAS)

Intervention Type: DEVICE

During each PAS run, bi-focal TMS (MagVenture, Farum, Denmark) is delivered to two brain areas while EEG/EMG (NeurOne, Bittium, Kuopio, Finland) are recorded. The asynchronies between the two TMS coils are kept constant within each session but differ across sessions. Within each session, to observe PAS effects on connectivity, uni-focal spTMS is delivered to the stimulated areas before and after the PAS modulation while EEG/EMG (NeurOne, Bittium, Kuopio, Finland) are recorded. In addition, resting-state EEG/EMG and a behavioral measure (bimanual task coordination) are recorded before and after the PAS modulation. An MRI-based TMS navigation system (Localite, Bonn, Germany) is used to navigate the TMS coils.

Interventions

Session 2: Single-pulse TMS (spTMS)

Uni-focal TMS (MagVenture, Farum, Denmark) is delivered to one brain area while EEG/EMG (NeurOne, Bittium, Kuopio, Finland) are recorded. The targeted brain areas and TMS intensities may vary across runs. An MRI-based TMS navigation system (Localite, Bonn, Germany) is used to navigate the TMS coil.

Intervention Type: DEVICE

Sessions 3 - 5: Paired associative stimulation (PAS)

During each PAS run, bi-focal TMS (MagVenture, Farum, Denmark) is delivered to two brain areas while EEG/EMG (NeurOne, Bittium, Kuopio, Finland) are recorded. The asynchronies between the two TMS coils are kept constant within each session but differ across sessions. Within each session, to observe PAS effects on connectivity, uni-focal spTMS is delivered to the stimulated areas before and after the PAS modulation while EEG/EMG (NeurOne, Bittium, Kuopio, Finland) are recorded. In addition, resting-state EEG/EMG and a behavioral measure (bimanual task coordination) are recorded before and after the PAS modulation. An MRI-based TMS navigation system (Localite, Bonn, Germany) is used to navigate the TMS coils.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Aapo Nummenmaa

Assistant in Neuroscience

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Aapo Nummenmaa, PhD

Role: STUDY_DIRECTOR

Massachusetts General Hospital

Locations

Mass General Brigham

Charlestown, Massachusetts, United States

Countries

United States

Central Contacts

Aapo Nummenmaa, PhD

Role: CONTACT

nummenma@mgh.harvard.edu

617-726-2000

Tommi Raij, MD, PhD

Role: CONTACT

raij@mgh.harvard.edu

617-726-2000

Facility Contacts

Aapo Nummenmaa, PhD

Role: primary

nummenma@mgh.harvard.edu

617-726-2000

Tommi Raij, MD, PhD

Role: backup

raij@mgh.harvard.edu

617-726-2000

Other Identifiers

R01NS126337-01 (pending)

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

R01NS126337-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2014p002652

Identifier Type: -

Identifier Source: org_study_id