Modulation of Motor Function by Stimulation of the Central and Peripheral Nervous System
Keywords
Abstract
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:
1. Aim 1. To identify resting behavioral and physiological substrates for neuromodulation of motor behavior
2. Aim 2. To identify task-dependent behavioral and physiological substrates for neuromodulation of motor behavior
3. 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 receive 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 are 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 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.
Dates
| Last Verified: | 02/03/2020 |
| First Submitted: | 03/27/2007 |
| Estimated Enrollment Submitted: | 03/27/2007 |
| First Posted: | 03/28/2007 |
| Last Update Submitted: | 10/01/2020 |
| Last Update Posted: | 10/04/2020 |
| Actual Study Start Date: | 01/13/2007 |
| Estimated Primary Completion Date: | 11/07/2019 |
| Estimated Study Completion Date: | 12/19/2019 |
Condition or disease
Intervention/treatment
Diagnostic Test: 1
Diagnostic Test: 1
Diagnostic Test: 1
Diagnostic Test: 1
Diagnostic Test: 1
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: 1 Healthy adults | Diagnostic Test: 1 The MRI studies were conducted on a 3 or 7 Tesla MRI scanner located in the NIH Magnetic Resonance Imaging Research Facility (NMRF), under the guidelines of the FDA, NIH, and NMRF. Subjects lie down in the scanner in a comfortable position, and will be monitored by investigators in the control room. They are able to communicate with the investigators by intercom at the operating console at all times. If subjects ask to stop the experiment, they will be removed immediately from the scanner. During the scan, the subjects hear a rhythmic tapping sound caused by the switching of the gradient coil that is necessary to produce the image. They are required to wear Nonmagnetic earplugs. The scanning session lasts up to approximately 2 hours. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| Criteria | - INCLUSION CRITERIA: 1. Age 18 and older 2. Willingness and ability to give consent 3. Normal neurological examination 4. Clearly dominant handedness (right or left) as assessed by Handedness scales EXCLUSION CRITERIA: 1. Any severe or progressive neurological disorder or severe medical condition, or history of seizures 2. 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. 3. 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 4. Diagnosis of drug dependence made by a health care provider (ICD-9-CM code 304) 5. Staff from our section |
Outcome
Primary Outcome Measures
1. Our overall goal in this protocol has been to optimize experimental protocols or stimulation parameters to collect pilot data in healthy volunteers for future patient-oriented hypothesis-driven protocols. [annually]
Secondary Outcome Measures
1. Aim 1. To identify resting behavioral and physiological substrates for neuromodulation of motor behavior [annually]
2. 2) Aim 2. To identify dependent behavioral and physiological substrates for neuromodulation of motor behavior. [annually]
3. 3) Aim 3. To understand variability, rigor or/and reproducibility of brain stimulation effects [annually]
