Recruiting

Observational Study

Sponsor:

Shirley Ryan AbilityLab

Code:

NCT03723434

Conditions

Healthy

Stroke

Traumatic Brain Injury

Multiple Sclerosis

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Single-pulse transcranial magnetic stimulation (spTMS)

Paired associative stimulation (PAS)

Repetitive transcranial magnetic stimulation (rTMS)

Study Details

Brief summary:

The purpose of this study is to understand the physiology of connectivity between cortical regions in the human brain in healthy participants and in patients with white matter lesions. Specifically, the investigators will examine the effects of paired associative stimulation (PAS) which consists in delivering brief (< 1 ms) current pulses separated by a short millisecond-level time interval ("asynchrony") to two cortical areas. The used techniques are all non-invasive and considered safe in humans: transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and functional MRI (fMRI). Based on prior literature in animals and human studies, it is hypothesized that PAS may increase or decrease effective connectivity between the stimulated areas depending on the asynchrony value. The main outcome measure is source-resolved EEG responses evoked by single-pulse TMS; this is a more direct measure of neuronal changes occurring at the targeted cortical area than motor evoked potentials (MEPs) or sensor-level EEG responses used in previous studies.

Conditions

Healthy

Stroke

Traumatic Brain Injury

Multiple Sclerosis

Study ID

NCT03723434

Start date

May 31, 2017

Status verified date

Oct, 2018

Completion date

Nov, 2020

Anticipated

Primary completion date

Nov, 2020

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

Inclusion Criteria for Healthy Participants:

  • Age from 18 to 85 years
  • Right-handed
  • Normal hearing and (corrected) vision
  • Able to understand and give informed consent
  • English speaker

Inclusion Criteria for Patients:

  • Age from 18 to 85 years
  • Stroke (ischemic subcortical, intermediate level, chronic phase 3 weeks or more from lesion)
  • TBI (closed-skull, intermediate level, chronic phase 3 weeks or more from lesion)
  • MS (white matter subcortical lesion)
  • Clinical and radiological evidence supporting the above diagnoses
  • One or more behavioral symptoms possibly linked to the white matter lesion(s)
  • Stable medical condition
  • English speaker

Exclusion Criteria:

Exclusion Criteria for Healthy Participants:

  • Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
  • Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or 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

Exclusion Criteria for Patients:

  • Same as above, excluding the requirement of no structural brain lesion, and medications influencing brain function are allowed
  • Patients with cortical lesions or CSF-filled cysts/cavities near the TMS sites
  • MS patients with acute exacerbation

Study Design

Enrollment

76 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

active comparator: Healthy Participants

Healthy participants without disorders or medications influencing brain function will be scanned with MRI and undergo single-pulse TMS and PAS during several visits, each with a different asynchrony, while EEG and MEPs are recorded.

experimental: Patients

Participants with stroke, traumatic brain injury (TBI), or multiple sclerosis (MS) will be scanned with MRI and undergo single-pulse TMS and paired associative stimulation during several visits while EEG is recorded.

Interventions

Single-pulse transcranial magnetic stimulation (spTMS)

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, St Augustin, Germany).

Paired associative stimulation (PAS)

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, St Augustin, Germany).

Repetitive transcranial magnetic stimulation (rTMS)

Repetitive TMS (rTMS) will be applied at 1 and 20 Hz with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. 300 rTMS pulses will be delivered during 1 and 20 Hz stimulation. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, St Augustin, Germany).

Primary outcome measure

  • Changes in EEG effective connectivity [ Time Frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session). ]
  • Changes in resting-state EEG coherence [ Time Frame: Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Within-session (before versus after PAS at 1 and 60 minutes). Across-sessions (persistence of changes up to 1 month after last PAS session). ]

Central Contacts and Locations

Central contacts

Tommi Raij, MD, PhD

312-238-4401tommi.raij@northwestern.edu

Julio C Hernandez Pavon, PhD, DSc

312-238-6820julio.hpavon@northwestern.edu

Locations

Shirley Ryan AbilityLab

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Tommi Raij, MD, PhD

312-238-4401tommi.raij@northwestern.edu

More Information

Sponsor

Shirley Ryan AbilityLab

Last update posted

Oct 29, 2018

Last verified

Oct, 2018

Keywords

  • Human
  • Brain
  • Connectivity
  • Stroke
  • Traumatic brain injury
  • Multiple sclerosis
  • Transcranial magnetic stimulation
  • Paired associative stimulation
  • Electroencephalography
  • Magnetic resonance imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Shirley Ryan AbilityLab on 2018-10-29.