Clinical trial NCT05288959: Modeling TMS-induced Cortical Network Activity
Official title: Modeling TMS-induced Cortical Network Activity
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Healthy
Keywords: human
brain
connectivity
paired associative stimulation
TMS-EEG
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2022-03-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Each subject serves as their own control. First, inter-regional conduction delays are measured in a uni-focal TMS session with EEG. Thereafter, bi-focal TMS (PAS) will be applied in three separate sessions, each using a different asynchrony. PAS may selectively increase or decrease effective connectivity depending on the asynchrony. Specifically, negative asynchronies (a few milliseconds shorter than the inter-regional conduction delay) are expected to decrease effective connectivity, zero asynchrony (equal to conduction delay) is predicted to have no effect, whereas positive asynchronies (a few milliseconds longer than the inter-regional conduction delay) are expected to increase it.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Cortico-cortical evoked potential (ccEP) latencies
timeFrame: 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.
measure: Change in cortico-cortical evoked potential (ccEP) amplitudes
timeFrame: Recorded in each bi-focal TMS (PAS) session, on average on Days 28, 35, and 42 (Sessions 3, 4, and 5, respectively).
Secondary outcomes:
measure: MRI structural connectivity
timeFrame: Once on Day 1 (Session 1, before first TMS session).
measure: MRI functional connectivity
timeFrame: Once on Day 1 (Session 1, before first TMS session).
measure: Change in bimanual coordination task (BCT) performance
timeFrame: Recorded in each bi-focal TMS (PAS) session, on average on Days 28, 35, and 42 (Sessions 3, 4, and 5, respectively).
measure: Change in resting-state EEG (rs-EEG) connectivity using phase slope index (PSI)
timeFrame: Recorded in each bi-focal TMS (PAS) session, on average on Days 28, 35, and 42 (Sessions 3, 4, and 5, respectively).
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Mass General Brigham
state: Massachusetts
Study officials:
affiliation: Mass General Brigham
name: Aapo Nummenmaa, PhD
role: STUDY_DIRECTOR
References: