Modulation of Motor Function by Stimulation of the Central and Peripheral Nervous System
Objectives
When a stroke damages the part of the brain that controls movement, people have weakness and difficulty using their hand. There is often some improvement, but many people have permanent disability in using the affected hand. Our previous research has shown that if we stimulate the nerves or the brain, we can temporarily improve how fast people with and without strokes can move their hands. But improvement is very slight and doesn t last long.
In this study, we are trying to see if different combinations of brain, skin and nerve stimulation might cause more improvement in motor function or learning. For this study, we will only include healthy people who have not had a stroke. We will use one or more types of electrical and magnetic stimulation of skin, nerves and the brain, or recording of behavior or brain activity alone without stimulation.
Study Population
Up to 1500 healthy volunteers, age 18 and older.
What will volunteers do in this study
Visits may include the following procedures:
Electromyography (EMG) which measures electrical activity of muscles.
Transcranial Magnetic Stimulation (TMS) where a wire coil is placed on the scalp, and brief electrical current creates a magnetic pulse that temporarily affect brain activity. This may feel like a pulling sensation where the coil is placed, and may result in twitches in the face, arm, or leg.
Transcranial direct current stimulation (tDCS), a technique in which a very weak electrical current is applied to the head in order to stimulate the brain.
Nerve Stimulation, where sticky pads or small metal disk electrodes attached to wires onto the skin to record muscle and nerve activity.
Magnetic resonance imaging (MRI) which uses a strong magnetic field and radio waves to take pictures of the brain. Some MRIs the volunteers are asked to lie still, and in others are asked to do various movements.
Magnetic resonance spectroscopy (MRS) uses a strong magnetic field and radio waves to take pictures of various chemicals in the brain using an MRI scanner.
Electroencephalogram (EEG) to record the electrical activity of the brain ( brain waves ).
Magnetoencephalography (MEG) records small magnetic field changes from brain activity.
Eye movement recordings
Behavioral Tests
Questionnaires
Pregnancy test (for those capable of getting pregnant)
How long is the study?
Volunteers in this study may have multiple visits. Each visit may last up to 8 hours. The number of visits we depend on the data the researchers want to collect. You may be asked to come back for visits over multiple years (up to 20 years). Taking part in this study is completely voluntary. People who volunteer to be in the study can change their mind at anytime.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Objectives
Noninvasive stimulation of the central and peripheral nervous system, including transcranial magnetic stimulation (TMS), transcranial direct and alternating current stimulation (tDCS and tACS, respectively) and cutaneous/peripheral nerve stimulation (C/PNS) alone or paired with TMS (paired associative stimulation, PAS), has been increasingly used in the investigation of cortical plasticity and as a possible adjuvant strategy in neurorehabilitation. It has been shown that TMS, tDCS, tACS and C/PNS can modulate motor function in healthy volunteers, as well as in patients with neurological disorders such as stroke.
One fundamental problem is that the optimal parameters of stimulation to modulate motor function by all of these techniques are not known. The purpose of this protocol has been to explore within safe guidelines, the effects of different stimulation parameters on motor cortical function, on oscillatory brain dynamics measured with magnetoencephalography (MEG) and electroencephalography (EEG), on eye movements, and on fMRI activation. In addition, this protocol was used to train new fellows coming to NINDS Human Cortical Physiology Section (HCPS) in the use of TMS, tDCS, tACS and C/PNS techniques.
We expected that information emerging from these studies would allow us to 1) optimize experimental protocols or stimulation parameters to collect pilot data in healthy volunteers for future patient-oriented hypothesis-driven protocols, 2) to collect pilot data for power analysis for future patient-oriented hypothesis driven protocols, and 3) to train new fellows in the use of these different methods.
As instructed, we had stopped recruitment under this protocol at the time we were informed by the NIH IRB that they determined this to be a thematic protocol (August 6, 2019). The four specific aims addressed under this protocol are:
- Aim 1. To identify resting behavioral and physiological substrates for neuromodulation of motor behavior
- Aim 2. To identify task-dependent behavioral and physiological substrates for neuromodulation of motor behavior
- Aim 3. To understand variability, rigor or/and reproducibility of brain stimulation effects.
As instructed, the purpose of this amendment is to request authorization to proceed with data analysis and publication. No new experiments will be carried out under this protocol.
Study Population
Up to 1500 healthy volunteers, age 18 and older.
Design
No new experiments will be carried out under this protocol. Previously, healthy volunteers received one or more of the following types of stimulation alone or in combination: (1) single- and paired-pulse TMS with inter-stimulus intervals of greater than 1s and up to 20s and intensities of up to 100% of stimulator output; (2) 1 Hz TMS for up to 30mins and up to 115% of resting motor threshold (RMT) intensity; (3) tDCS applied at an intensity of up to 4 mA for a duration of up to 60mins, as long the total charge does not exceed 7.2 C; (4) tACS applied at a peak-to-peak intensity of up to 4 mA for a duration of up to 60 minutes, as long the total charge does not exceed 7.2 C; (5) C/PNS applied alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours, or intensities up to 300% of sensory threshold when C/PNS is paired with TMS. All of these parameters of stimulation and procedures have safely been used as previously reported in the literature. Sham stimulations were delivered for each modality as scientifically needed. Some sessions included recording of behavior or brain activity (such as behavioral testing, MRI, and MEG) if brain stimulation targets were unknown. This information was used to inform the design of brain stimulation protocols.
Each subject was able to participate in up to one experimental session per day, and up to 20 total sessions over a twenty year period under this protocol. A single session lasted no longer than 8 hours. Appropriate rest breaks and meal breaks occured during long sessions. CTDB was used to track the number of sessions per subject to ensure they did not exceed 20 sessions. Protocol AIs were responsible for entering the subjects/sessions into CTDB.
We previously tested the effects of different forms of stimulation on motor cortical excitability, cognitive and motor behavioral tasks, and brain state measures derived from neuroimaging data (i.e. - MRI, fMRI, MEG and EEG). Stimulation was be applied before, after, or during physiological (i.e. motor evoked potentials, M-wave, F-wave, or H-Reflexes), neuroimaging or behavioral measures.
Outcome Measures
No new outcome measures are proposed. Changes in motor cortical excitability were previously measured as the change in the average peak-to-peak amplitude of a motor evoked potential (MEP) as measured with EMG. Neuroimaging measures included changes in oscillatory brain activity power as measured with EEG or MEG, changes in BOLD fMRI activation or changes in functional connectivity (i.e. covarying fluctuations in BOLD or spectral power across the brain). Behavioral outcome measures focused on changes in performance as a function of learning, or as a function of applied brain stimulation.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
INCLUSION CRITERIA:
- Age 18 and older
- Willingness and ability to give consent
- Normal neurological examination
- Clearly dominant handedness (right or left) as assessed by Handedness scales
EXCLUSION CRITERIA:
- Any severe or progressive neurological disorder or severe medical condition, or history of seizures
- Chronic use of medications acting primarily on the central nervous system, which lower the seizure threshold or significantly alter cortical excitability such as antipsychotic drugs (chlorpromazine, clozapine), tricyclic or other antidepressants, or prescription stimulants.
- Pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments
- Diagnosis of drug dependence made by a health care provider (ICD-9-CM code 304)
- Staff from our section
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 1
Healthy Volunteers
|
<=1 Hz TMS for up to 30mins and up to 115% of resting motor threshold intensity (MT).
|
|
Sham Comparator: 1a
Healthy Volunteers
|
<=1 Hz TMS for up to 30mins and up to 115% of resting motor threshold intensity (MT).
|
|
Experimental: 2
Healthy Volunteers
|
tDCS up to 2 mA for up to 60mins.
|
|
Sham Comparator: 2a
Healthy Volunteers
|
tDCS up to 2 mA for up to 60mins.
|
|
Experimental: 3
Healthy Volunteers
|
tACS up to 1 mA for up to 10 minutes.
|
|
Sham Comparator: 3a
Healthy Volunteers
|
tACS up to 1 mA for up to 10 minutes.
|
|
Experimental: 4
Healthy Volunteers
|
CPNS alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours.
|
|
Sham Comparator: 4a
Healthy Volunteers
|
CPNS alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To identify task-dependent behavioral and physiological substrates for neuromodulation of motor behavior Aim
Time Frame: in data analysis
|
in data analysis
|
in data analysis
|
|
To understand variability, rigor or/and reproducibility of brain stimulation effects.
Time Frame: in data analysis
|
in data analysis
|
in data analysis
|
|
To identify resting behavioral and physiological substrates for neuromodulation of motor behavior Aim
Time Frame: in data analysis
|
in data analysis
|
in data analysis
|
Collaborators and Investigators
Investigators
- Principal Investigator: Leonardo G Cohen, M.D., National Institute of Neurological Disorders and Stroke (NINDS)
Publications and helpful links
General Publications
- Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. doi: 10.1016/s0168-5597(97)00096-8.
- Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain. 1994 Aug;117 ( Pt 4):847-58. doi: 10.1093/brain/117.4.847.
- Muellbacher W, Ziemann U, Boroojerdi B, Hallett M. Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior. Clin Neurophysiol. 2000 Jun;111(6):1002-7. doi: 10.1016/s1388-2457(00)00284-4.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 070122
- 07-N-0122
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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