Physiology of Interregional Connectivity in the Human Brain

NCT03723434 | Unknown

• 1 other identifier: STU00204239
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Changes in EEG effective connectivity

  EEG will be recorded with a 64-channel whole-head TMS-compatible device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) 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-PAS) and at 1 (Post-PAS T1) and at 60 minutes after PAS (Post-PAS T60).

  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

  Resting-state EEG will be recorded with a 64-channel whole-head device (NeurOne, Bittium, Kuopio, Finland). Data will be collected before (Pre-PAS) and at 1 minute (Post-PAS T1) and at 60 minutes (Post-PAS T60) after PAS. Resting-state EEG coherence will be computed in the source space for the two areas receiving PAS from 1 to 100 Hz.

  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).

Secondary Outcomes (3)

• Motor evoked potentials (MEPs)

  Experiment A: Within-session (before versus after PAS at 1 and 60 minutes). Experiment B: Done only in patients where the M1 was targeted with PAS.

• MRI functional connectivity

  Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.

• MRI structural connectivity

  Experiment A: Baseline. Experiment B: Baseline to 1 month after the last PAS session.

Study Arms (2)

Healthy Participants

ACTIVE COMPARATOR

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.

Device: Single-pulse transcranial magnetic stimulation (spTMS); Device: Paired associative stimulation (PAS); Device: Repetitive transcranial magnetic stimulation (rTMS)

Patients

EXPERIMENTAL

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.

Device: Single-pulse transcranial magnetic stimulation (spTMS); Device: Paired associative stimulation (PAS)

Interventions

Single-pulse transcranial magnetic stimulation (spTMS) DEVICE

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).

Healthy Participants; Patients

Paired associative stimulation (PAS) DEVICE

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).

Healthy Participants; Patients

Repetitive transcranial magnetic stimulation (rTMS) DEVICE

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).

Healthy Participants

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shirley Ryan AbilityLab: lead
• Northwestern University: collaborator

Study Sites (1)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Stroke; Brain Injuries, Traumatic; Multiple Sclerosis

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Tommi Raij, MD, PhD

  Shirley Ryan AbilityLab 355 East Erie St, Chicago, IL Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University, Chicago, IL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tommi Raij, MD, PhD

CONTACT

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

Julio C Hernandez Pavon, PhD, DSc

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Scientist, Brain Stimulation Director

Model Details: PAS will be applied to two cortical targets at 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.

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 29, 2018
• Study Start: May 31, 2017
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: October 29, 2018

Record last verified: 2018-10

Locations

US (1)