Brain Injuries
Conditions
Keywords
Electrophysiology, Magnetic Resonance imaging (MRI), Neuroanatomy, Neuroscience
Brief summary
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.
Detailed description
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.
Interventions
DEVICETranscranial 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.
OTHERSham TMS
Sham Transcranial Magnetic Stimulation (TMS)
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* No history of movement impairment or neurodegenerative disease * Right handedness * No contraindication to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI).
Exclusion criteria
* Participants that are outside the age range of 18-85 * Have a history of head trauma or neurodegenerative disorder * Report contraindications to TMS. * Participants over age 65 will be asked to complete the Montreal Cognitive Assessment, and participants with a score of 25 or lower (out of the normal range) will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serial Reaction Time Task (SRTT) Performance | Pre-test (baseline), Post-test (training usually lasts for 3 hours), Retention Test (30 mins following training) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | Pre-test (baseline), Post-test (training usually lasts for 3 hours) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham TMS Sham brain stimulation | 20 |
| 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. | 20 |
| 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. | 24 |
| Total | 64 |
Baseline characteristics
| Characteristic | Sham TMS | TMS Over Primary Motor Cortex (M1) | TMS Over Premotor Cortex (PMC) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 24 Participants | 64 Participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 5 Participants | 1 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Multi racial | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 13 Participants | 15 Participants | 39 Participants |
| Region of Enrollment United States | 20 Participants | 20 Participants | 24 Participants | 64 Participants |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 16 Participants | 42 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 8 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 24 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 24 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 24 |
Outcome results
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.
Time frame: Pre-test (baseline), Post-test (training usually lasts for 3 hours), Retention Test (30 mins following training)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham TMS | Serial Reaction Time Task (SRTT) Performance | SS Pre-test | 31 milliseconds (ms) | Standard Deviation 38 |
| Sham TMS | Serial Reaction Time Task (SRTT) Performance | SS Retention Testing | 31 milliseconds (ms) | Standard Deviation 25 |
| Sham TMS | Serial Reaction Time Task (SRTT) Performance | SS Post-test | 24 milliseconds (ms) | Standard Deviation 21 |
| TMS Over Primary Motor Cortex (M1) | Serial Reaction Time Task (SRTT) Performance | SS Pre-test | 35 milliseconds (ms) | Standard Deviation 19 |
| TMS Over Primary Motor Cortex (M1) | Serial Reaction Time Task (SRTT) Performance | SS Retention Testing | 40 milliseconds (ms) | Standard Deviation 23 |
| TMS Over Primary Motor Cortex (M1) | Serial Reaction Time Task (SRTT) Performance | SS Post-test | 30 milliseconds (ms) | Standard Deviation 22 |
| TMS Over Premotor Cortex (PMC) | Serial Reaction Time Task (SRTT) Performance | SS Retention Testing | 29 milliseconds (ms) | Standard Deviation 11 |
| TMS Over Premotor Cortex (PMC) | Serial Reaction Time Task (SRTT) Performance | SS Post-test | 17 milliseconds (ms) | Standard Deviation 23 |
| TMS Over Premotor Cortex (PMC) | Serial Reaction Time Task (SRTT) Performance | SS Pre-test | 38 milliseconds (ms) | Standard Deviation 24 |
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.
Time frame: Pre-test (baseline), Post-test (training usually lasts for 3 hours)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham TMS | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | MEP Amplitude Pre-test | 1.03 millivolts (mV) | Standard Deviation 0.97 |
| Sham TMS | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | MEP Amplitude Post-test | 1.15 millivolts (mV) | Standard Deviation 1.03 |
| TMS Over Primary Motor Cortex (M1) | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | MEP Amplitude Pre-test | 1.29 millivolts (mV) | Standard Deviation 1.22 |
| TMS Over Primary Motor Cortex (M1) | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | MEP Amplitude Post-test | 1.37 millivolts (mV) | Standard Deviation 1.24 |
| TMS Over Premotor Cortex (PMC) | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | MEP Amplitude Pre-test | 0.45 millivolts (mV) | Standard Deviation 0.37 |
| TMS Over Premotor Cortex (PMC) | Cortical Excitability Measured by Motor Evoked Potentials (MEPs) | MEP Amplitude Post-test | 0.51 millivolts (mV) | Standard Deviation 0.53 |