Cortical Contributions to Motor Sequence Learning

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Characterizing Cortical Contributions to Motor Sequence Learning

Conditions
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Brain Injuries

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation (TMS)
* Other: Sham TMS


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMS over premotor cortex<br>Noninvasive brain stimulation in the premotor cortex | Device: Transcranial Magnetic Stimulation (TMS)<br>* 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.<br>* Other names: TMS;|
| Experimental: TMS over primary motor cortex<br>Noninvasive brain stimulation in the motor cortex | Device: Transcranial Magnetic Stimulation (TMS)<br>* 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.<br>* Other names: TMS;|
| Sham Comparator: Sham TMS over premotor cortex<br>Sham brain stimulation in the premotor cortex | Other: Sham TMS<br>* Sham Transcranial Magnetic Stimulation (TMS) over premotor cortex<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in skill after training | Degree of sequence learning after receiving one of three types of stimulation: premotor cortex stimulation, primary motor cortex stimulation, or sham stimulation. Sequence-specific motor learning will be indexed by the difference in response time for repeated sequence responses compared to random sequence responses. | Day 1 Post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cortical excitability after sequence learning. | 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. | Day 1 post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electrophysiology, Magnetic Resonance imaging (MRI), Neuroanatomy, Neuroscience