Cortical Contributions to Motor Sequence Learning

Characterizing Cortical Contributions to Motor Sequence Learning

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.

Study Overview

• Status: Completed
• Conditions: Brain Injuries
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation (TMS); Other: Sham TMS

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30329
      • Wesley Woods

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMS over premotor cortex (PMC); Noninvasive brain stimulation in the premotor cortex	Device: 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.; Other Names: TMS
Experimental: TMS over primary motor cortex (M1); Noninvasive brain stimulation in the motor cortex	Device: 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.; Other Names: TMS
Sham Comparator: Sham TMS; Sham brain stimulation	Other: Sham TMS; Sham Transcranial Magnetic Stimulation (TMS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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.	Pre-test (baseline), Post-test (training usually lasts for 3 hours)

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Michael Borich, DPT, PhD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2019
• Primary Completion (Actual): August 4, 2023
• Study Completion (Actual): August 4, 2023

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: October 23, 2019
• First Posted (Actual): October 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 2, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Neuroscience; Electrophysiology; Neuroanatomy; Magnetic Resonance imaging (MRI)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries
• Other Study ID Numbers: IRB00115009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Neurophysiology and motor performance outcome measures will be shared
• IPD Sharing Time Frame: . Data will be available after publication of primary study results (estimated 12 months after study completion - no end date specified)
• IPD Sharing Access Criteria: Data will be shared through secure file transfer to researchers requesting access to data collected as part of this study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No