Cortical Contributions to Motor Sequence Learning

Not Applicable

Completed

• Conditions: Brain Injuries
• Interventions: Device: Transcranial Magnetic Stimulation (TMS); Other: Sham TMS

• Registration Number: NCT04138953
• Lead Sponsor: Emory University

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-10-23
• Study First Submitted QC: 2019-10-23
• Study First Posted: 2019-10-25
• Study Start: 2019-12-05
• Primary Completion: 2023-08-04
• Study Completion: 2023-08-04
• Status Verified: 2024-08
• Results First Submitted: 2024-08-02
• Results First Submitted QC: 2024-08-02
• Last Update Submitted: 2024-08-02
• Results First Posted: 2024-08-28
• Last Update Posted: 2024-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• No history of movement impairment or neurodegenerative disease
• Right handedness
• No contraindication to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TMS over primary motor cortex (M1)	Transcranial Magnetic Stimulation (TMS)	Noninvasive brain stimulation in the motor cortex
Sham TMS	Sham TMS	Sham brain stimulation
TMS over premotor cortex (PMC)	Transcranial Magnetic Stimulation (TMS)	Noninvasive brain stimulation in the premotor cortex

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

Wesley Woods; 🇺🇸 Atlanta, Georgia, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States