Modeling TMS-induced Cortical Network Activity

Healthy Clinical Trial

Official title:

Modeling TMS-induced Cortical Network Activity

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05288959
• Other study ID #: 2014p002652
• Secondary ID: R01NS126337-01 (
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2022
• Est. completion date: March 31, 2027

Study information

• Verified date: March 2022
• Source: Massachusetts General Hospital
• Contact: Aapo Nummenmaa, PhD
• Phone: 617-726-2000
• Email: nummenma[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: March 31, 2027
• Est. primary completion date: March 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Mass General Brigham	Charlestown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cortico-cortical evoked potential (ccEP) latencies	EEG/EMG are recorded with a 64/16-channel TMS-compatible device (NeurOne, Bittium, Kuopio, Finland) while spTMS is delivered. Thereafter, the sensor-space evoked potentials (EPs) undergo EEG source analysis to produce source-space ccEPs. For sessions with uni-focal TMS, the ccEPs latencies are used for determining the inter-regional conduction delays.	Recorded in the uni-focal TMS session, on average on Day 14 (Session 2). The ccEPs are measured once for each TMS location and intensity.
Primary	Change in cortico-cortical evoked potential (ccEP) amplitudes	EEG/EMG are recorded with a 64/16-channel TMS-compatible device (NeurOne, Bittium, Kuopio, Finland) while spTMS is delivered. Thereafter, the sensor-space evoked potentials (EPs) undergo EEG source analysis to produce source-space ccEPs. For sessions with bi-focal TMS (PAS), the ccEPs amplitudes are used for determining the within-session effects of PAS by measuring the change in amplitudes before versus after the PAS modulation.	Recorded in each bi-focal TMS (PAS) session, on average on Days 28, 35, and 42 (Sessions 3, 4, and 5, respectively).
Secondary	MRI structural connectivity	Diffusion MRI will be used to assess structural connectivity strengths between the stimulated areas in bi-focal TMS (PAS). The structural connectivity strengths will be compared with EEG-derived connectivity strengths.	Once on Day 1 (Session 1, before first TMS session).
Secondary	MRI functional connectivity	Resting-state fMRI will be used to assess functional connectivity strengths between the stimulated areas in bi-focal TMS (PAS). The functional connectivity strengths will be compared with EEG-derived connectivity strengths.	Once on Day 1 (Session 1, before first TMS session).
Secondary	Change in bimanual coordination task (BCT) performance	Behavioral measures of inter-hemispheric communication between the left and right motor cortices will be recorded with the BCT. Change is measured by comparing performance before vs. after the PAS modulation.	Recorded in each bi-focal TMS (PAS) session, on average on Days 28, 35, and 42 (Sessions 3, 4, and 5, respectively).
Secondary	Change in resting-state EEG (rs-EEG) connectivity using phase slope index (PSI)	EEG/EMG are recorded with a 64/16-channel TMS-compatible device (NeurOne, Bittium, Kuopio, Finland) during rest. Thereafter, unaveraged source-space time courses are extracted from the sensor-space EEG using source analysis techniques. The source-space time courses from the stimulated areas are analyzed for signs of connectivity changes by comparing the within-session PSI values before versus after the PAS modulation.	Recorded in each bi-focal TMS (PAS) session, on average on Days 28, 35, and 42 (Sessions 3, 4, and 5, respectively).