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The long-term objective initiated with this study is to determine which brain areas functionally contribute to learning a motor skill. The primary hypothesis of this trial is that premotor cortex (PMC) is necessary to learn a new motor skill. Participants may undergo a MRI scan to acquire a structural image of their brain to target noninvasive stimulation, using transcranial magnetic stimulation (TMS) to one of two brain areas: PMC or primary motor cortex (M1). A third group of individuals will undergo a placebo stimulation protocol. For all three groups, stimulation will be used to create a transient 'virtual lesion' during motor skill training. Temporarily disrupting the normal activity of these brain regions during training will allow us to determine which regions are causally involved in learning a new motor skill. The primary outcome measure will be the change in skill after training in each group.
Recent findings in humans suggest that motor sequences are represented in the premotor cortex once learned. Studies in animal models have also shown that the premotor cortical areas encode sequence-specific information. However, it is currently unknown if premotor cortical areas are involved in the acquisition or consolidation of sequences in humans. In this project, the investigators will evaluate the functional contributions of human premotor cortex to sequence learning. The primary overarching research objective is to determine the brain regions causally involved in motor skill acquisition and consolidation. The main hypothesis is that disrupting premotor cortex activity during motor sequence learning will reduce the acquisition and consolidation of the skill. Transcranial magnetic stimulation (TMS) will be used to temporarily disrupt activity of premotor cortex or primary motor cortex, and skill learning will be assessed in both groups. A sham stimulation group, where participants will feel the coil on their head and hear the click of the TMS pulses but not actually receive stimulation to the brain, will be used as a control. Participants will be randomly assigned to be in the premotor cortex, primary motor cortex, or sham stimulation group. Participants may be asked to undergo a Magnetic Resonance Imaging (MRI) scan at Wesley Woods prior to TMS testing, which will occur at the Emory Rehabilitation Hospital. The MRI scan would be used to help target TMS to the intended brain area. Participants will be recruited using flyers around the local community. Consent forms will be provided with ample time for the participant to read it over and ask any questions that may arise. Participants will be compensated for their time. The proposed work will be the first to evaluate the causal role of premotor cortex in motor sequence learning in humans. Findings from this project are expected to inform the design and application of therapeutic interventions that improve motor functioning and learning in clinical populations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TMS over premotor cortex (PMC) | Experimental | Noninvasive brain stimulation in the premotor cortex |
|
| TMS over primary motor cortex (M1) | Experimental | Noninvasive brain stimulation in the motor cortex |
|
| Sham TMS | Sham Comparator | Sham brain stimulation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Device | Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
| Measure | Description | Time Frame |
|---|---|---|
| Serial Reaction Time Task (SRTT) Performance | The SRTT involves pressing a key that corresponds to a target square presented on a monitor. Sequenced skill (SS) is calculated by subtracting the response time of sequenced key presses from random key presses within and across a test block. An increase in SS value indicates an increase in sequenced skill and is a preferable result. | Pre-test (baseline), Post-test (training usually lasts for 3 hours), Retention Test (30 mins following training) |
| Measure | Description | Time Frame |
|---|---|---|
| Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | Evaluate the effect of sequence learning on motor cortical excitability. Cortical excitability will be indexed by peak-to-peak amplitudes of transcranial magnetic stimulation (TMS)-evoked electromyographic responses in the hand contralateral to the motor cortex targeted by TMS quantified before and after training. An increase in MEPs indicates neural plasticity due to increases in skill. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Borich, DPT, PhD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States | ||
| Wesley Woods |
Neurophysiology and motor performance outcome measures will be shared
. Data will be available after publication of primary study results (estimated 12 months after study completion - no end date specified)
Data will be shared through secure file transfer to researchers requesting access to data collected as part of this study
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham TMS | Sham brain stimulation |
| FG001 | TMS Over Primary Motor Cortex (M1) | Noninvasive brain stimulation in the motor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
| FG002 | TMS Over Premotor Cortex (PMC) | Noninvasive brain stimulation in the premotor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sham TMS | Sham brain stimulation |
| BG001 | TMS Over Primary Motor Cortex (M1) | Noninvasive brain stimulation in the motor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serial Reaction Time Task (SRTT) Performance | The SRTT involves pressing a key that corresponds to a target square presented on a monitor. Sequenced skill (SS) is calculated by subtracting the response time of sequenced key presses from random key presses within and across a test block. An increase in SS value indicates an increase in sequenced skill and is a preferable result. | The population in this analysis includes participants who completed the indicated study visit and had usable data. Five participants in the PMC group are not included due to technical issues; for 2 participants the stimulation target could not be confirmed during data analysis and 3 participants had different timing values than other members of their cohort. Of participants with usable pre- and post- test data, 11 from the M1 group and 12 from the PMC group completed the retention test. | Posted | Mean | Standard Deviation | milliseconds (ms) | Pre-test (baseline), Post-test (training usually lasts for 3 hours), Retention Test (30 mins following training) |
|
Adverse events were collected for the entire duration of participation, from the time of informed consent through completing the retention testing, up to 28 hours.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sham TMS | Sham brain stimulation | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Borich, DPT, PhD | Emory University | 404-712-0612 | michael.borich@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 20, 2019 | Jul 30, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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|
|
| Sham TMS | Other | Sham Transcranial Magnetic Stimulation (TMS) |
|
| Pre-test (baseline), Post-test (training usually lasts for 3 hours) |
| Atlanta |
| Georgia |
| 30329 |
| United States |
| BG002 | TMS Over Premotor Cortex (PMC) | Noninvasive brain stimulation in the premotor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Sham TMS |
Sham brain stimulation |
| OG001 | TMS Over Primary Motor Cortex (M1) | Noninvasive brain stimulation in the motor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
| OG002 | TMS Over Premotor Cortex (PMC) | Noninvasive brain stimulation in the premotor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. |
|
|
| Secondary | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | Evaluate the effect of sequence learning on motor cortical excitability. Cortical excitability will be indexed by peak-to-peak amplitudes of transcranial magnetic stimulation (TMS)-evoked electromyographic responses in the hand contralateral to the motor cortex targeted by TMS quantified before and after training. An increase in MEPs indicates neural plasticity due to increases in skill. | The population in this analysis includes participants who completed the indicated study visit and had usable data. Five participants in the premotor cortex (PMC) group are not included due to technical issues; for two participants the stimulation target could not be confirmed during data analysis and three participants had different timing values than other members of their cohort. | Posted | Mean | Standard Deviation | millivolts (mV) | Pre-test (baseline), Post-test (training usually lasts for 3 hours) |
|
|
|
| 20 |
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | TMS Over Primary Motor Cortex (M1) | Noninvasive brain stimulation in the motor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. | 0 | 20 | 0 | 20 | 0 | 20 |
| EG002 | TMS Over Premotor Cortex (PMC) | Noninvasive brain stimulation in the premotor cortex Transcranial Magnetic Stimulation (TMS): Transcranial magnetic stimulation, also known as repetitive transcranial magnetic stimulation, is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. It will be used to create a 'virtual lesion,' disrupting neural activity in a specific brain region to identify whether it is causally involved in a specific behavioral process. | 0 | 24 | 0 | 24 | 0 | 24 |
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| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
|