Normal PhysiologyNCT03018262
Neurophysiology of Surround Inhibition in the Human Motor Cortex
An observational study of Normal Physiology, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Movement disorders have many different causes and symptoms. Researchers still do not fully understand which parts of the brain are involved in fine movement. They want to learn about which brain regions could be abnormal in people with movement disorders. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Physiology
- What is being tested?
- TMS - sub-study 1, TMS - sub-study 2 and TMS - sub-study 3
- Type of treatment
- Medical device
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2017to 24 Mar 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy Volunteers
Who may be able to join
- Age between 18 - 70 years.
- Right-handed (tested by the Edinburg handedness inventory).
- Able to give informed consent.
- Able to comply with all study procedures.
- Abstain from alcohol for at least 48 hrs prior to the study and caffeine on the day of the study (based on oral interview).
Who cannot join
- Illegal drug use within the past 6 months based on history alone. The intent is to exclude those with drug use that may affect study results.
- Self-reported consumption of >14 alcoholic drinks/week for a man and >7 alcoholic drinks/week for a woman.
- Abnormal findings on neurological examination.
- History of or current brain tumor, stroke, head trauma with loss of consciousness, epilepsy or seizures.
- Current episode of major depression or any major psychiatric illness.
- Taking medications that act directly on the central nervous system such as anti-epileptics, anti-histamines, anti-parkinsonian medication, muscle relaxants, medication for insomnia, anti-depressants, anti-anxiety medication.
Show all 19Show fewer
- Presence of any metal in the eye or skull area such as a brain stimulator, shrapnel, surgical metal, clips in the brain, cochlear implants, metal fragments in the eye.
- Presence of pacemaker, intracardiac lines, implanted pumps or stimulators or metal objects inside the eye or skull.
- Known hearing loss.
- NIH employees and/or staff.
- Pregnancy
- We will follow the Clinical Radiology/NMR Center guidelines for MR safety.
- Some of the exclusions are:
- Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear implants, artificial heart valves or metal fragments in the eye as these make having an MRI unsafe.
- Have metallic dental fillings which are likely to cause MRI artifacts
- Unable to lie flat on the back for the expected length of the experiment,
- up to 30 mins.
- Uncomfortable being in a small space for the expected length of the experiment, up to 30 mins.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Detailed Evaluation of the Neurophysiology of Surround Inhibition in the Human Motor Cortex
Background:
Movement disorders have many different causes and symptoms. Researchers still do not fully understand which parts of the brain are involved in fine movement. They want to learn about which brain regions could be abnormal in people with movement disorders.
Read more
Objective:
To better understand how the brain controls movement.
Eligibility:
Healthy, right-handed adults age 18-70 years old.
Design:
Participants will be screened with a physical exam and questions about their handedness. They may have a urine test.
Participants will have 1 or 2 clinic visits. The first visit will last about 1.5 hours. The second will last about 3 hours.
Participants will have structural magnetic resonance imaging (MRI). A strong magnetic field and radio waves take pictures of the brain. Participants will lie on a table that slides in and out of a metal cylinder.
Participants may have transcranial magnetic stimulation. A wire coil is held on the scalp. A brief electrical current is passed through the coil and creates a magnetic pulse that stimulates the brain. Participants will wear a pair of glasses or a headband with small sensors so researchers can track head position.
Participants will perform a simple index finger movement task.
Participants may have surface electromyography from at least two hand muscles. Small metal disk or adhesive pad electrodes will be taped to the skin. Participants will be seated in a comfortable chair with their hands placed on a pillow.
Participants may have an electroencephalography. A cap with small disc electrodes will be placed on the scalp.
Read the detailed description
Objectives:
The purpose of this protocol is to improve understanding of the neurophysiological mechanisms that underlie the phenomenon of surround inhibition in the human motor cortex. It is known that patients with focal hand dystonia have abnormal motor surround inhibition. However, the physiology of this phenomenon still remains unclear. The 3 sub-studies proposed under this protocol will integrate several neurophysiological techniques to explore different aspects of motor surround inhibition. The objectives of sub-study 1 are (a) to identify the EEG correlate of motor SI (b) to determine the relationship between short interval intracortical inhibition (SICI) and SI, both of which are compromised in patients with FHD and (c) to determine if there is an oscillatory frequency band that is relevant for SI. The results from this sub-study will shed light on the inhibitory mechanisms that are critical for motor SI. Sub-study 2 is aimed at determining the influence of parietal conditioning on motor surround inhibition. If conditioning the parietal cortex enhances SI, we can conclude that the parieto-motor inhibitory network may be involved in motor SI and that this network could be affected in focal hand dystonia. Sub-study 3 will explore SI during different motor tasks.
Study population:
We intend to study up to 95 healthy volunteers in total. Up to 30 participants will be recruited for sub-study 1, 35 for sub-study 2, and 30 for sub-study 3.
Design:
Sub-study 1: This will be an exploratory study. Participants will perform an auditory cued index finger movement task and motor evoked potentials will be elicited by stimulating the motor hotspot of a surround muscle using transcranial magnetic stimulation (TMS). EEG will be recorded continuously. Single or paired TMS pulses (with postero-anterior or antero-posterior current) will be delivered either while the subject is at rest or at movement onset. TMS-evoked potentials (TEPs) will be obtained by time-locked averaging of all the trials in each condition. The amplitudes of the different peaks of the TEP will be compared across conditions which may be correlated with the degree of SI or SICI. The components of the TEP that are most relevant to motor SI will thus be identified.
Sub-study 2: This will be a hypothesis-driven study. Our primary hypothesis is that parietal conditioning will influence motor SI in healthy volunteers. Participants will perform an auditory cued index finger movement task and motor evoked potentials will be elicited by stimulating the motor hotspot of a surround muscle using transcranial magnetic stimulation. Two coils, one positioned over the motor cortex and the other over an inhibitory region of the inferior parietal lobule, will deliver TMS pulses at a fixed inter-stimulus interval. The pulses will be delivered either while the subject is at rest or at movement onset. The ratio of mean MEP amplitude obtained with parietal conditioning to that obtained with motor cortex stimulation alone at movement onset will reveal any parieto-motor influence on SI.
Sub-study 3: This will be an exploratory study. Participants will be asked to perform different motor tasks such as activating an intrinsic hand muscle at different levels of activation, sequential muscle activation or more complex tasks such as writing. Single TMS pulses will be delivered at primary motor cortex at rest, at the onset of the motor tasks or during the motor tasks. MEPs will be measured in the active and surround muscles. The ratios of MEP amplitudes during different levels of activation in the active and surround muscles will reveal
modulation of SI during these tasks.
Outcome measures:
For sub-study 1, our outcome measures will be (1) amplitudes of the different TEP peaks (2) degree of surround inhibition and short interval intracortical inhibition (3) correlation between them and relevant peak amplitudes (4) power and cortico-cortical coherence at different frequency bands.
MEP amplitude will be the primary outcome measure in sub-study 2 and 3.
- Conditions
- Normal Physiology
- Being tested
- TMS - sub-study 1, TMS - sub-study 2, TMS - sub-study 3
- Keywords
- Surround Inhibition, Motor Control, Transcranial Magnetic Stimulation (TMS), TMS-Evoked Potential
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMS - sub-study 1Device
TMS pulses will be applied to the motor hotspot of the surround muscle to identify the TMS-evoked potentials corresponding to motor surround inhibition (SI)
TMS - sub-study 2Device
TMS will be used to stimulate the motor cortex and an inhibitory region of the inferior parietal lobe
TMS - sub-study 3Device
TMS pulses will be delivered to the primary motor cortex at rest, at the onset of the motor task, or during the motor task
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteers - Sub-study 1 | Healthy Volunteers Receives: Device: TMS - sub-study 1 | |
| Healthy Volunteers - Sub-study 2 | Healthy Volunteers Receives: Device: TMS - sub-study 2 | |
| Healthy Volunteers - Sub-study 3 | Healthy Volunteers Receives: Device: TMS - sub-study 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Substudy 2 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single /paired pulse TMS at rest or movement onset will give information about the corticospinal excitability.
TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single/paired pulse TMS at rest or movement onset will give information about the corticospinal excitability.
Measured: throughout
Substudy 1 EEG analysis: we will measure the latency and amplitude of the different components of the TMS-evoked potentials
EEG: For the EEG analysis, we will measure the latency and amplitude of the different components of the TMS-evoked potentials. Time-frequency analysis on the collected EEG data will provide valuable information on which frequency bands are involved in the phenomenon of motor SI. The coherence calculated between relevant brain regions will also reveal information on the changes in cortical connectivity during the phenomenon of SI.
Measured: throughout
Substudy 1 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal
TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single/paired pulse TMS will give information about the corticospinal excitability. The latency of the MEP will revealmore information on which neuronal networks were activated.
Measured: throughout
Substudy 3 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single pulse TMS at rest or during a motor task will give information about the corticospinal excitability.
TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single pulse TMS at rest or during a motor task will give information about the corticospinal excitability.
Measured: throughout
Substudy 3 EMG: The EMG amplitude during certain tasks will reveal information about the level of muscle activation.
EMG: The EMG amplitude during certain tasks will reveal information about the level of muscle activation.
Measured: throughout
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2017 (estimated)
- Study start7 Feb 2017
- Primary completion24 Mar 2021
- Study completion24 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Hallett, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03018262
- Sponsor's protocol ID
- 170031
- Other IDs
- 17-N-0031
- Status last verified
- Nov 2023
- First submitted
- 11 Jan 2017
- Last updated
- 24 Nov 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detailed Evaluation of the Neurophysiology of Surround Inhibition in the Human Motor Cortex
- ClinicalTrials.gov ID
- NCT03018262
- Acronym / sponsor ID
- 170031
- Conditions
- Normal Physiology
- Keywords
- Surround Inhibition, Motor Control, Transcranial Magnetic Stimulation (TMS), TMS-Evoked Potential
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 7 Feb 2017 (actual)
- Primary completion
- 24 Mar 2021 (actual)
- Study completion
- 24 Mar 2021 (actual)
- First posted
- 12 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Movement disorders have many different causes and symptoms. Researchers still do not fully understand which parts of the brain are involved in fine movement. They want to learn about which brain regions could be abnormal in people with movement disorders.
Objective:
To better understand how the brain controls movement.
Eligibility:
Healthy, right-handed adults age 18-70 years old.
Design:
Participants will be screened with a physical exam and questions about their handedness. They may have a urine test.
Participants will have 1 or 2 clinic visits. The first visit will last about 1.5 hours. The second will last about 3 hours.
Participants will have structural magnetic resonance imaging (MRI). A strong magnetic field and radio waves take pictures of the brain. Participants will lie on a table that slides in and out of a metal cylinder.
Participants may have transcranial magnetic stimulation. A wire coil is held on the scalp. A brief electrical current is passed through the coil and creates a magnetic pulse that stimulates the brain. Participants will wear a pair of glasses or a headband with small sensors so researchers can track head position.
Participants will perform a simple index finger movement task.
Participants may have surface electromyography from at least two hand muscles. Small metal disk or adhesive pad electrodes will be taped to the skin. Participants will be seated in a comfortable chair with their hands placed on a pillow.
Participants may have an electroencephalography. A cap with small disc electrodes will be placed on the scalp.
Detailed description
Objectives:
The purpose of this protocol is to improve understanding of the neurophysiological mechanisms that underlie the phenomenon of surround inhibition in the human motor cortex. It is known that patients with focal hand dystonia have abnormal motor surround inhibition. However, the physiology of this phenomenon still remains unclear. The 3 sub-studies proposed under this protocol will integrate several neurophysiological techniques to explore different aspects of motor surround inhibition. The objectives of sub-study 1 are (a) to identify the EEG correlate of motor SI (b) to determine the relationship between short interval intracortical inhibition (SICI) and SI, both of which are compromised in patients with FHD and (c) to determine if there is an oscillatory frequency band that is relevant for SI. The results from this sub-study will shed light on the inhibitory mechanisms that are critical for motor SI. Sub-study 2 is aimed at determining the influence of parietal conditioning on motor surround inhibition. If conditioning the parietal cortex enhances SI, we can conclude that the parieto-motor inhibitory network may be involved in motor SI and that this network could be affected in focal hand dystonia. Sub-study 3 will explore SI during different motor tasks.
Study population:
We intend to study up to 95 healthy volunteers in total. Up to 30 participants will be recruited for sub-study 1, 35 for sub-study 2, and 30 for sub-study 3.
Design:
Sub-study 1: This will be an exploratory study. Participants will perform an auditory cued index finger movement task and motor evoked potentials will be elicited by stimulating the motor hotspot of a surround muscle using transcranial magnetic stimulation (TMS). EEG will be recorded continuously. Single or paired TMS pulses (with postero-anterior or antero-posterior current) will be delivered either while the subject is at rest or at movement onset. TMS-evoked potentials (TEPs) will be obtained by time-locked averaging of all the trials in each condition. The amplitudes of the different peaks of the TEP will be compared across conditions which may be correlated with the degree of SI or SICI. The components of the TEP that are most relevant to motor SI will thus be identified.
Sub-study 2: This will be a hypothesis-driven study. Our primary hypothesis is that parietal conditioning will influence motor SI in healthy volunteers. Participants will perform an auditory cued index finger movement task and motor evoked potentials will be elicited by stimulating the motor hotspot of a surround muscle using transcranial magnetic stimulation. Two coils, one positioned over the motor cortex and the other over an inhibitory region of the inferior parietal lobule, will deliver TMS pulses at a fixed inter-stimulus interval. The pulses will be delivered either while the subject is at rest or at movement onset. The ratio of mean MEP amplitude obtained with parietal conditioning to that obtained with motor cortex stimulation alone at movement onset will reveal any parieto-motor influence on SI.
Sub-study 3: This will be an exploratory study. Participants will be asked to perform different motor tasks such as activating an intrinsic hand muscle at different levels of activation, sequential muscle activation or more complex tasks such as writing. Single TMS pulses will be delivered at primary motor cortex at rest, at the onset of the motor tasks or during the motor tasks. MEPs will be measured in the active and surround muscles. The ratios of MEP amplitudes during different levels of activation in the active and surround muscles will reveal
modulation of SI during these tasks.
Outcome measures:
For sub-study 1, our outcome measures will be (1) amplitudes of the different TEP peaks (2) degree of surround inhibition and short interval intracortical inhibition (3) correlation between them and relevant peak amplitudes (4) power and cortico-cortical coherence at different frequency bands.
MEP amplitude will be the primary outcome measure in sub-study 2 and 3.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteers - Sub-study 1 | – | Device: TMS - sub-study 1Healthy Volunteers |
| Healthy Volunteers - Sub-study 2 | – | Device: TMS - sub-study 2Healthy Volunteers |
| Healthy Volunteers - Sub-study 3 | – | Device: TMS - sub-study 3Healthy Volunteers |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy Volunteers
Key inclusion criteria (5 listed)
- Age between 18 - 70 years.
- Right-handed (tested by the Edinburg handedness inventory).
- Able to give informed consent.
- Able to comply with all study procedures.
- Abstain from alcohol for at least 48 hrs prior to the study and caffeine on the day of the study (based on oral interview).
Key exclusion criteria (19 listed)
- Illegal drug use within the past 6 months based on history alone. The intent is to exclude those with drug use that may affect study results.
- Self-reported consumption of >14 alcoholic drinks/week for a man and >7 alcoholic drinks/week for a woman.
- Abnormal findings on neurological examination.
- History of or current brain tumor, stroke, head trauma with loss of consciousness, epilepsy or seizures.
- Current episode of major depression or any major psychiatric illness.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMS - sub-study 1TMS pulses will be applied to the motor hotspot of the surround muscle to identify the TMS-evoked potentials corresponding to motor surround inhibition (SI) | Device | Healthy Volunteers - Sub-study 1 |
| TMS - sub-study 2TMS will be used to stimulate the motor cortex and an inhibitory region of the inferior parietal lobe | Device | Healthy Volunteers - Sub-study 2 |
| TMS - sub-study 3TMS pulses will be delivered to the primary motor cortex at rest, at the onset of the motor task, or during the motor task | Device | Healthy Volunteers - Sub-study 3 |
Primary outcome
Substudy 2 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single /paired pulse TMS at rest or movement onset will give information about the corticospinal excitability.
Time frame: throughout
TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single/paired pulse TMS at rest or movement onset will give information about the corticospinal excitability.
Substudy 1 EEG analysis: we will measure the latency and amplitude of the different components of the TMS-evoked potentials
Time frame: throughout
EEG: For the EEG analysis, we will measure the latency and amplitude of the different components of the TMS-evoked potentials. Time-frequency analysis on the collected EEG data will provide valuable information on which frequency bands are involved in the phenomenon of motor SI. The coherence calculated between relevant brain regions will also reveal information on the changes in cortical connectivity during the phenomenon of SI.
Substudy 1 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal
Time frame: throughout
TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single/paired pulse TMS will give information about the corticospinal excitability. The latency of the MEP will revealmore information on which neuronal networks were activated.
Substudy 3 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single pulse TMS at rest or during a motor task will give information about the corticospinal excitability.
Time frame: throughout
TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single pulse TMS at rest or during a motor task will give information about the corticospinal excitability.
Substudy 3 EMG: The EMG amplitude during certain tasks will reveal information about the level of muscle activation.
Time frame: throughout
EMG: The EMG amplitude during certain tasks will reveal information about the level of muscle activation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Hallett, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normal Physiology, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Substudy 2 TMS: The amplitude of the motor evoked potential (MEP) in the EMG signal elicited by single /paired pulse TMS at rest or movement onset will give information about the corticospinal excitability. (time frame: throughout). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.