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Influence of Brain Oscillation-Dependent TMS on Motor Function

This study is currently recruiting participants.
Verified September 18, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Sponsor:
ClinicalTrials.gov Identifier:
NCT03288220
First Posted: September 20, 2017
Last Update Posted: December 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
  Purpose

Background:

When people have a stroke, they often have difficulty moving their arms and hands. Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke can move their arms and hands. But the effects of TMS are minor, and it doesn t work for everyone. Researchers want to study how to time brain stimulation so that the effects are more consistent.

Objective:

To understand how the brain responds to transcranial magnetic stimulation so that treatments for people with stroke can be improved.

Eligibility:

Adults ages 18 and older who had a stroke at least 6 months ago

Healthy volunteers ages 18 and older

Design:

Participants will have up to 5 visits.

At visit 1, participants will be screened with medical history and physical exam. Participants with stroke will also have TMS and surface electromyography (sEMG).

For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple movements during TMS.

For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded.

At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the loud noise.

At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG, small electrodes on the scalp will record brainwaves. Participants will sit still, watch a movie, or do TMS.

Participants may be asked to have 2 extra visits to redo procedures.


Condition
Stroke Normal Physiology Aging

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Other
Official Title: Influence of Brain Oscillation-Dependent TMS on Motor Function

Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):

Primary Outcome Measures:
  • Corticospinal Excitability [ Time Frame: Ongoing ]

Secondary Outcome Measures:
  • Effective Intracortical Connectivity [ Time Frame: Ongoing ]

Estimated Enrollment: 74
Anticipated Study Start Date: December 20, 2017
Estimated Study Completion Date: July 3, 2021
Estimated Primary Completion Date: May 26, 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts
Stroke patients
--Age 18 and over; Mild to moderate unilateral or bilateral upper limb hemiparesis; Stroke onset > 6 months prior to participation
Healthy young adults
Healthy young adults--Age 18-59
Healthy older adults
Healthy older adults--Age 60 and over

Detailed Description:

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been customarily applied uncoupled from brain oscillatory activity (as measured using EEG waveforms), resulting in variability in the biological response to each stimulus, small effect sizes and significant inter-individual variability. Brain oscillatory activity (i.e., EEG waveform oscillatory activity) in the alpha band (8-12 Hz) is linked to cortical inhibition, motor function and cognitive processing, and therefore influences brain function. For example, corticospinal excitability (as measured with TMS) in healthy humans varies depending on the sensorimotor alpha oscillatory phase during which TMS is delivered: corticospinal excitability is higher when TMS is delivered during sensorimotor alpha oscillation troughs (i.e., maximum surface negativity) and lower when TMS is delivered during sensorimotor alpha oscillation peaks (i.e., maximum surface positivity). Here, we will first attempt replication of this result using closed-loop TMS in young healthy adults (Experiment 1). Subsequently, we aim to extend these findings to two new populations: healthy older adults (Experiment 2), and patients with chronic stroke (Experiment 3). Previous studies have demonstrated that older adults exhibit significant differences in motor cortical physiology compared to young adults, so Experiment 2 will be performed to determine whether a similar association between sensorimotor alpha oscillatory phase and corticospinal excitability is present in healthy aging. Finally, Experiment 3 will be performed to determine if the expected association between sensorimotor alpha oscillatory phase and corticospinal excitability is also present after chronic stroke. Importantly, acquiring information regarding how the aged and damaged brain respond to EEG waveform oscillation-dependent closed-loop TMS will be critical for developing more effective TMS-based (i.e., closed-loop) interventions. In all experiments, TMS delivery will be timed to specific sensorimotor alpha oscillation phases. We expect the results of this work to provide new insights into how corticospinal excitability is affected by sensorimotor alpha oscillation phase, which could lead to more effective use of sensorimotor alpha oscillation-dependent neuromodulatory TMS protocols in the future.

STUDY POPULATION: Up to 24 young healthy volunteers (ages 18-59), up to 24 older healthy volunteers (ages 60 and older), and up to 26 stroke patients (age 18 and older).

DESIGN: Each experiment will begin with MRI to allow for co-registration with a frameless stereotactic device for the precise targeting of TMS. In Experiment 1, healthy young adults will receive single-pulse, closed-loop TMS to the motor cortex hand area (M1-hand) during sensorimotor alpha oscillation (a) troughs (i.e., maximum surface negativity), (b) peaks (i.e., maximum surface positivity), and (c) uncoupled from sensorimotor alpha oscillation phase (as measured with EEG) using a within-subject design. In Experiment 2, healthy older adults will complete the same procedures described for Experiment 1. In Experiment 3, chronic stroke patients will also complete the same procedures described for Experiment 1, except that TMS will be delivered to the ipsilesional M1-hand. For each experiment, up to 700 single-pulse TMS pulses will be delivered (excluding pulses used to identify scalp hotspot and resting motor threshold), and all subjects will be given rest breaks as needed.

OUTCOME MEASURES: For all experiments, the primary outcome measure is corticospinal excitability. The secondary outcome measure is effective intracortical connectivity between M1 and the rest of the brain. Exploratory outcome measures include MEP amplitude variability, TMS-induced oscillations, and resting state EEG brain connectivity.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy young adults -Age 18-59; -Healthy older adults -Age 60 and over; Stroke patients
Criteria
  • INCLUSION CRITERIA:
  • Healthy young adults:

    • Age 18-59
    • Willingness/ability to provide informed consent
  • Healthy older adults:

    • Age 60 and over
    • Willingness/ability to provide informed consent

Stroke patients:

  • Age 18 and over
  • Mild to moderate unilateral or bilateral upper limb hemiparesis
  • Stroke onset > 6 months prior to participation
  • Intact M1 sufficient to induce motor evoked potentials in the affected hand/wrist following ipsilesional TMS, as evaluated during the TMS Screening.
  • Willingness/ability to provide informed consent

    • If the investigator feels the individual s capacity to provide informed consent is questionable, the NIH Human Subjects Protection Unit (HSPU) will be requested to determine the individual s ability to consent.

EXCLUSION CRITERIA:

  • Healthy young adults:

    • Presence of severe neurological or medical disorder (e.g. Parkinson s disease or multiple sclerosis)
    • History of seizures
    • Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), tri-cyclic or other anti-depressants, benzodiazepines or prescription stimulants
    • MRI contraindications, as per NMR Center MRI Safety Screening Questionnaire, such as metal implants and pregnancy. Pregnancy for women of childbearing potential will be assessed using pregnancy test within 24 hours preceding MRI procedures.
    • TMS contraindications, such as:

      • Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside the eye or skull
      • Hearing loss
    • Staff from our section
  • Healthy older adults:

    • Presence of severe neurological or medical disorder (e.g. Parkinson s disease or multiple sclerosis)
    • History of seizures
    • Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), tri-cyclic or other anti-depressants, benzodiazepines or prescription stimulants
    • MRI contraindications, as per NMR Center MRI Safety Screening Questionnaire, such as metal implants and pregnancy. Pregnancy for women of childbearing potential will be assessed using pregnancy test within 24 hours preceding MRI procedures.
    • TMS contraindications, such as:

      • Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside the eye or skull
      • Hearing loss
    • Staff from our section
  • Stroke patients:

    • Presence of severe neurological or medical disorder, other than stroke (e.g. Parkinson s disease or multiple sclerosis)
    • History of brainstem stroke
    • History of seizures
    • Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), benzodiazepines or prescription stimulants
    • MRI contraindications, as per NMR Center MRI Safety Screening Questionnaire, such as metal implants and pregnancy. Pregnancy for women of childbearing potential will be assessed using pregnancy test within 24 hours preceding MRI procedures.
    • TMS contraindications, such as:

      • Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside the eye or skull
      • Hearing loss
    • Staff from our section
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03288220


Contacts
Contact: Sara Hussain, Ph.D. (301) 594-1484 sara.hussain@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Principal Investigator: Leonardo G Cohen, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT03288220     History of Changes
Other Study ID Numbers: 170168
17-N-0168
First Submitted: September 19, 2017
First Posted: September 20, 2017
Last Update Posted: December 15, 2017
Last Verified: September 18, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Stroke