Healthy
Conditions
Keywords
Paired Associative Stimulation, Transcranial Magnetic Stimulation, Electroencephalography, Effective Connectivity, Human Brain
Brief 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.
Interventions
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).
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_TESTMagnetic resonance imaging (MRI)
Structural, diffusion, and functional MRI with a 3-Tesla Siemens scanner
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
Participants will not be informed of the asynchrony value for each visit. The order of asynchronies is randomized.
Intervention model description
PAS will be applied to two cortical targets at a minimum of 3 different asynchronies to modulate connectivity. PAS may selectively increase or decrease effective connectivity depending on the asynchrony. Negative asynchronies are expected to decrease effective connectivity, whereas positive asynchronies to increase it. All participants will be stimulated with all 3 asynchronies (on different visits).
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Age from 18 to 64 years * Right-handed * Normal hearing and (corrected) vision * Able to understand and give informed consent
Exclusion criteria
* Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps * Metal in the body (e.g., rods, plates, screws, shrapnel, dentures that cannot be removed during the recordings, IUD) * Suspected metallic particles in the eye * Surgical clips in the head or previous neurosurgery * Any magnetic particles in the body * Cochlear implants * Prosthetic heart valves * Epilepsy or any other type of seizure history * Any neurological diagnoses or medications influencing brain function * History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae) * Known structural brain lesion * Significant other disease (heart disease, malignant tumors, mental disorders) * Significant claustrophobia; Ménière's disease * Pregnancy (ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible), breast feeding * Non prescribed drug use * Failure to perform the behavioral tasks or neuropsychological evaluation tests * Prisoners
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in EEG effective connectivity | Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS) | EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne 64, Bittium, Kuopio, Finland). Data will be collected before (Pre) and at 5 minutes (Post-1) and at 60 minutes (Post-2) after PAS. To record spTMS-evoked EEG responses the investigators will deliver 80 single TMS pulses to the two areas receiving PAS, one target after the other in separate runs. Effective connectivity will be measured by comparing the source-resolved EEG evoked response waveforms before (Pre) and at 5 (Post-1) and at 60 minutes after PAS (Post-2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in resting-state EEG coherence | Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS) | Resting-state EEG will be recorded with a 64-channel whole-head device (NeurOne 64, Bittium, Kuopio, Finland). Data will be collected before (Pre) and at 5 minutes (Post-1) and at 60 minutes (Post-2) after PAS. Resting-state EEG coherence will be computed in the source space for the two areas receiving PAS. |
| Changes in bimanual coordination task performance | Within-session (Before PAS, 5 minutes after PAS, 60 minutes after PAS) | Participants will engage in a simple bimanual coordination task before (Pre), 5 minutes following (Post-1), and 60 minutes following (Post-2) PAS application for the purpose of providing behavioral data on inter-hemisphere connections between the motor cortices. The measure will be quantified by comparisons between participant task performance pre- and post- PAS application. |
Countries
United States
Contacts
Primary ContactNetri Pajankar, MS
Backup ContactGabriel Fadel, MS
Outcome results
None listed