Modulation of Motor Function by Stimulation of the Central and Peripheral Nervous System

NCT00453505 | Completed Early Phase 1

• 2 other identifiers: 07012207-N-0122
• Study Type: interventional
• Target: 1,007
• Locations: 1 country
• Sites: 1

Brief Summary

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 is 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 will be 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 expect that information emerging from these studies will allow us to 1) optimize experimental protocols or stimulation parameters to collect pilot data in healthy volunteer 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. Study Population Up to 1500 healthy volunteers, age 18 and older. Design Healthy volunteers will 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, 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 will be delivered for each modality as scientifically needed. Some substudies may involve recording of behavior or brain activity only (such as behavioral testing, MRI, and MEG) if brain stimulation targets are unknown. This information can help design future brain stimulation protocols. Each subject may participate in up to 20 sessions. A single session may last no longer than 8 hours to allow for initial testing paradigm followed by retests or performing other components of the same substudy later in the day. Appropriate rest breaks and meal breaks will occur during long sessions. Subjects participate in one experimental session per day under this protocol. The 20 experimental sessions will be scheduled over a twenty-year period. CTDB is used to track the number of sessions per subject so it does not exceed 20 sessions. The AIs are responsible for entering the subjects/sessions into CTDB. We will test the effects of these 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 may be applied before, after, or during physiological (i.e. motor evoked potentials, M-wave, F-wave, or H-Reflexes), neuroimaging or behavioral measures. Under this protocol, we conduct: Exploratory Sub-studies: These substudies are exploratory in nature and are conducted in order to develop information to generate better informed future hypotheses and/or power analyses. We have set an upper limit of 40 subjects per sub-study. Hypothesis-Testing Sub-studies: Hypothesis-testing sub-studies are studies with specific hypotheses to be tested. These sub-studies undergo statistical and PIRC review after 6 subjects per group (e.g., after 12 subjects, 6 per arm, if two groups are studied), before additional subjects can be recruited. Together, the P.I. and PIRC will decide whether to continue the sub-study with more subjects without an amendment or whether an amendment or protocol would be necessary. A memo requesting a review of hypothesis-testing sub-studies for possible additional enrollment (beyond 6) will be sent to PIRC and the statistical reviewer. This protocol is ......

Conditions

Motor Function of Healthy Physiology

Keywords

Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation; Peripheral Nerve Stimulation; Primary Motor Cortex; Corticomotor Excitability; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (3)

• To identify task-dependent behavioral and physiological substrates for neuromodulation of motor behavior Aim

  in data analysis

  in data analysis

• To understand variability, rigor or/and reproducibility of brain stimulation effects.

  in data analysis

  in data analysis

• To identify resting behavioral and physiological substrates for neuromodulation of motor behavior Aim

  in data analysis

  in data analysis

Study Arms (8)

1

EXPERIMENTAL

Healthy Volunteers

Device: TMS

1a

SHAM COMPARATOR

Healthy Volunteers

Device: TMS

2

EXPERIMENTAL

Healthy Volunteers

Device: tDCS

2a

SHAM COMPARATOR

Healthy Volunteers

Device: tDCS

3

EXPERIMENTAL

Healthy Volunteers

Device: tACS

3a

SHAM COMPARATOR

Healthy Volunteers

Device: tACS

4

EXPERIMENTAL

Healthy Volunteers

Device: CPNS

4a

SHAM COMPARATOR

Healthy Volunteers

Device: CPNS

Interventions

TMS DEVICE

\<=1 Hz TMS for up to 30mins and up to 115% of resting motor threshold intensity (MT).

1; 1a

tDCS DEVICE

tDCS up to 2 mA for up to 60mins.

2; 2a

tACS DEVICE

tACS up to 1 mA for up to 10 minutes.

3; 3a

CPNS DEVICE

CPNS alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours.

4; 4a

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 and older
• Willingness and ability to give consent
• Normal neurological examination
• Clearly dominant handedness (right or left) as assessed by Handedness scales

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 9474057 BACKGROUND

• 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.

  PMID: 7922470 BACKGROUND

• 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.

  PMID: 10825706 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Transcranial Direct Current Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Leonardo G Cohen, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2007
• First Posted: March 29, 2007
• Study Start: January 14, 2007
• Primary Completion: November 8, 2019
• Study Completion: December 20, 2019
• Last Updated: May 7, 2026

Record last verified: 2025-06-11

Locations

US (1)