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

NCT ID: NCT05351255

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2026-12-19

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.

Detailed Description

Cerebellar damage causes the disabling movement disorder ataxia, which is characterized by impaired movement coordination affecting all body movements. In the arms, ataxia causes reaching movements with irregular, oscillating, and prolonged trajectory paths. People with cerebellar ataxia (PWCA) are also impaired in an important form of motor learning, called adaptation, which normally keeps movement well calibrated. In prior research, the principal investigator showed that PWCA can learn to correct their reaching movements if they instead employ reinforcement learning (RL). Although many PWCA learned optimally in RL conditions, this prior work found variability across individuals: some learned more than others. While adaptation critically relies on cerebellar integrity, RL depends more heavily on dopaminergic circuitry in the midbrain and excitatory plasticity in M1. Cerebellar damage has been shown to increase intracortical inhibition in M1, which may hamper the plasticity needed for RL. The repetitive TMS protocols of continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) have further been shown to modulate intracortical inhibition: cTBS decreases it, while iTBS increases it. Here, the investigators will systematically test whether increased intracortical inhibition in M1 predicts RL capacity (Aim 1) and whether modulating inhibition in M1 can alter RL capacity in PWCA (Aim 2). 12 PWCA from a degenerative condition will complete 4 experimental sessions over a 6-month period. In session 1, TMS will be used to assess baseline recruitment curves for corticomotor excitability and short-interval intracortical inhibition, and the cortical silent period. PWCA will then complete a standardized clinical rating of their ataxia severity and an established behavioral task that requires learning a reaching skill using the RL paradigm. In sessions 2-4, PWCA will complete 3 additional sessions of the RL task. In each session, PWCA will receive cTBS, iTBS, or sham stimulation to modulate intracortical inhibition in M1 prior to performing the RL task. For Aim 1, the investigators will use multi-level regression to quantify relationships between TMS measures of M1 state and the magnitude and speed of learning in the RL task. For Aim 2, the investigators will use multi-level modeling to quantify differences in the magnitude and speed of learning across stimulation conditions. The investigators hypothesize that increased baseline inhibition in M1 will show a positive association with a lower magnitude and speed of learning in the RL task (Aim 1), and cTBS will improve the magnitude of learning, the speed of learning, or both, in the RL task relative to iTBS or sham stimulation (Aim 2).

Conditions

Cerebellar Ataxia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

rTMS Intervention

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.

Group Type: EXPERIMENTAL

Transcranial Magnetic Stimulation (TMS)

Intervention Type: 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.

Interventions

Transcranial Magnetic Stimulation (TMS)

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Albert Einstein Healthcare Network

OTHER

Sponsor Role: lead

Responsible Party

Amanda Therrien, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amanda S Therrien, PhD

Role: PRINCIPAL_INVESTIGATOR

Moss Rehabilitation Research Institute

Locations

Moss Rehabilitation Research Institute

Elkins Park, Pennsylvania, United States

Countries

United States

Other Identifiers

P2CHD086844

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AEHN-IRB-2022-881

Identifier Type: -

Identifier Source: org_study_id