Motor Learning After Cerebellar Damage: The Role of the Primary Motor Cortex

NCT05351255 | Active Not Recruiting

• 2 other identifiers: AEHN-IRB-2022-881P2CHD086844
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine (1) whether baseline inhibitory activity in the primary motor cortex can predict motor learning ability in individuals with cerebellar degeneration, and (2) whether modulating primary motor cortex activity with non-invasive brain stimulation alters motor learning ability in this population.

Conditions

Cerebellar Ataxia

Outcome Measures

Primary Outcomes (7)

• International Cooperative Ataxia Rating Scale Total Score

  The sore out of 100 that results from assessment using the International Cooperative Ataxia Rating Scale (ICARS). The rating scale has a minimum score of 0 and a maximum score of 100. Higher scores indicate more severe impairment.

  Baseline

• International Cooperative Ataxia Rating Scale Limb Coordination Sub-Score

  The score out of 52 that results from assessment using the Limb Kinetic sub-section of the International Cooperative Ataxia Rating Scale (ICARS). The Limb Kinetic sub-score has a minimum score of 0 and a maximum score of 52. Higher scores indicate more severe impairment.

  Baseline

• Reinforcement Learning Rate

  The slope of the time series of reach path lengths (determined from digital 3D kinematic data recorded using a motion capture system) over the first 80 trials of the intervention phase of the reinforcement motor learning task.

  During the intervention, assessed up to 10 days

• Total Reinforcement Learning

  The difference in mean reach path length (determined from digital 3D kinematic data recorded using a motion capture system) between the baseline phase and the end of the intervention phase of the reinforcement motor learning task.

  During the intervention, assessed up to 10 days

• Slope of the Corticomotor Excitability Recruitment Curve

  The slope of motor evoked potential amplitudes (determined from electromyographic recordings of target muscle activity) between TMS intensities of 120-140% of resting motor threshold.

  Baseline

• Slope of the Short-Interval Intracortical Inhibition (SICI) Recruitment Curve

  SICI will be computed as the difference in average motor evoked potential amplitude (determined from electromyographic recordings of target muscle activity) between a TMS condition where a single conditioning pulse is applied 3 ms before a single test pulse and a TMS condition where only the test pulse is applied. A range of conditioning pulse TMS intensities will be tested and SICI will be measured for each. The outcome measure comprises the slope of the SICI values over each conditioning pulse intensity.

  Baseline

• Cortical Silent Period

  Single pulses of TMS will be applied at an intensity of 110% of resting motor threshold while participants tonically activate the target muscle at 20% of their maximum voluntary isometric contraction. 12 repetitions of the protocol will be performed. The outcome measure comprises the average time, in ms, from the end of the motor evoked potential to the reoccurrence of tonic background electromyographic activity.

  Baseline

Study Arms (1)

rTMS Intervention

EXPERIMENTAL

In aim 2 of the study, participants receive a repetitive transcranial magnetic stimulation intervention called theta burst stimulation (TBS) to study its effect on motor learning behavior. All participants will complete 3 sessions in which they will receive continuous TBS, intermittent TBS, or sham TBS before completing a behavioral motor learning task. The order of TBS sessions will be counter-balanced across participants.

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

Transcranial Magnetic Stimulation (TMS) DEVICE

Aim 2 of the study includes an intervention where participants receive a repetitive TMS protocol called theta burst stimulation (TBS) to study its effect on motor learning behavior.

rTMS Intervention

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of cerebellar ataxia from cerebellar degeneration
• Normal or corrected-to-normal vision
• Normal or corrected-to-normal hearing
• Meet safety criteria for receipt of transcranial magnetic stimulation

You may not qualify if:

• Extrapyramidal signs on neurologic examination
• History of alcohol or illicit drug abuse
• Peripheral sensory loss in the arms
• Cognitive or attention deficits that interfere with testing, the capacity to understand and follow task instructions, or the capacity to provide informed consent
• Orthopedic injury or pain in the arms

Sponsors & Collaborators

• Albert Einstein Healthcare Network: lead
• Medical University of South Carolina: collaborator

Study Sites (1)

Moss Rehabilitation Research Institute

Elkins Park, Pennsylvania, 19027, United States

Location

MeSH Terms

Conditions

Cerebellar Ataxia

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Amanda S Therrien, PhD

  Moss Rehabilitation Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 6, 2022
• First Posted: April 28, 2022
• Study Start: July 1, 2022
• Primary Completion (Estimated): December 19, 2026
• Study Completion (Estimated): December 19, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Coded IPD data will be made available to other researchers immediately after publication, in compliance with the requirements of many academic journals in the motor control neuroscience field.
• Access Criteria: Coded IPD and additional supporting information will be made available via a published repository on the Moss Rehabilitation Research Institute Sensorimotor Learning Laboratory Git Hub website. Requests for access to IPD will be reviewed by the study PI. Agreement to properly cite the original repository will be a requirement for approval of access.

Locations

US (1)