Using Real-time fMRI Neurofeedback and Motor Imagery to Enhance Motor Timing and Precision in Cerebellar Ataxia

Using Real-time Functional Magnetic Resonance Imaging (fMRI) Neurofeedback and Motor Imagery to Enhance Motor Timing and Precision in Cerebellar Ataxia

The aim of the research is to improve motor function in people with cerebellar ataxia by using neuroimaging methods and mental imagery to "exercise" motor networks in the brain. The relevance of this research to public health is that results have the potential to reduce motor deficits associated with cerebellar atrophy, thereby enhancing the quality of life and promoting independence.

Study Overview

• Status: Completed
• Conditions: Cerebellar Ataxia; Spinocerebellar Ataxias; Cerebellar Degeneration
• Intervention / Treatment: Device: Real-time fMRI with neurofeedback of motor imagery

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-100 years of age
• At least 8th-grade education
• Right-handedness
• Clinical diagnosis of progressive, degenerative cerebellar ataxia by a movement disorder specialist (cerebellar ataxia of unknown etiology, and spinocerebellar ataxias with and without genetic confirmation)

Exclusion Criteria:

• History of Axis I psychiatric disorders (including alcohol and drug dependence)
• Severe or unstable medical disorder, neurological disorders, such as stroke or epilepsy
• History of head injury that resulted in a loss of consciousness greater than 5 minutes and/or neurological sequelae
• Any condition that is contraindicated for the MRI environment (e.g., metal in the body, pacemaker, claustrophobia)
• Currently pregnant
• Clinical diagnosis of multiple system atrophy (MSA) or Friedrich's ataxia (FA)
• Eligible subjects may be asked to refrain from medications that affect the central nervous system that would also make data difficult to interpret (e.g., sedatives) for an appropriate period of time prior to scanning
• Participants will be excluded if the participants do not have a home computer with internet available to complete the 3-week at-home component of the study protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real time neurofeedback with task and at-home finger tapping practice sessions; Participants will undergo a real-time fMRI scan during which two distinct tasks will be performed. Neurofeedback treatment: During the fMRI scan, the tasks consist of: Overt finger tapping in time with a flashing cue.; Motor imagery (of finger tapping). During overt finger tapping, feedback will consist of a slider bar that indicates tapping accuracy to target speed (1 or 4Hz). During motor imagery, neurofeedback will consist of a crosshair that flashes to indicate the success of recruiting predicted brain regions (consistent with those engaged during overt tapping). At-home therapy: Participants are assigned to one of two groups where participants will practice each day 17 sessions total at-home. Group 1: Overt finger tapping on 17 daily sessions. Participants will finger tap in time with the flashing cue.	Device: Real-time fMRI with neurofeedback of motor imagery; Participants undergo a real-time fMRI scan during which they are provided feedback regarding the accuracy of their motor imagery performance.
Experimental: Real time neurofeedback with task and at-home motor imagery practice sessions; Participants will undergo a real-time fMRI scan during which two distinct tasks will be performed. Neurofeedback treatment: During the fMRI scan, the tasks consist of: Overt finger tapping in time with a flashing cue.; Motor imagery (of finger tapping). During overt finger tapping, feedback will consist of a slider bar that indicates tapping accuracy to target speed (1 or 4Hz). During motor imagery, neurofeedback will consist of a crosshair that flashes to indicate the success of recruiting predicted brain regions (consistent with those engaged during overt tapping). At-home therapy: Participants are assigned to one of two groups where participants will practice each day 17 sessions total at-home. Group 2: Motor imagery only on 13 daily sessions, and overt finger tapping only on 4 daily sessions.	Device: Real-time fMRI with neurofeedback of motor imagery; Participants undergo a real-time fMRI scan during which they are provided feedback regarding the accuracy of their motor imagery performance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 1Hz Speed	During the MRI session, accuracy on overt tapping will be measured by the distance of the actual tapping rate vs. target rate (1Hz). Accuracy at baseline will be compared to that of final assessment, which will take place before and after neurofeedback training, respectively. The difference in accuracy between the two tests create a delta measure (i.e., fewer errors in the final vs. baseline tests). This delta accuracy will indicate the magnitude of tapping accuracy improvements. Root mean squared error (RMSE) is the measure for both the baseline and post-treatment behavioral tasks. RMSE will be based on the actual number of taps per second relative to the expected number of taps per second (e.g., 1 tap for 1Hz). Then post treatment RMSE minus baseline RMSE will determine a delta RMSE. A higher RMSE signifies greater error. For the delta measure, it is expected, lower scores reflect greater improvement on the task.	Baseline and MRI duration, up to 1 hour
Change in Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 4Hz Speed	During the MRI session, accuracy on overt tapping will be measured by the distance of the actual tapping rate vs. target rate (4Hz). Accuracy at baseline will be compared to that of final assessment, which will take place before and after neurofeedback training, respectively. The difference in accuracy between the two tests create a delta measure (i.e., fewer errors in the final vs. baseline tests). This delta accuracy will indicate the magnitude of tapping accuracy improvements. Root mean squared error (RMSE) is the measure for both the baseline and post-treatment behavioral tasks. RMSE will be based on the actual number of taps per second relative to the expected number of taps per second (e.g., 1 tap for 1Hz). Then post treatment RMSE minus baseline RMSE will determine a delta RMSE. A higher RMSE signifies greater error. For the delta measure, it is expected, lower scores reflect greater improvement on the task.	Baseline and MRI duration, up to 1 hour
Change in At-home Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 1Hz Speed	Accuracy at baseline will be compared to that of final assessment, which will take place before and after the 3-week at-home practice sessions, respectively. The delta measure will indicate the magnitude of tapping accuracy improvements. Groups will be compared to examine differences in delta as a function of practice condition (tapping only or imagery plus tapping). RMSE (root mean squared error) is the measure for both the baseline and post-treatment behavioral tasks. RMSE will be based on the actual number of taps per second relative to the expected number of taps per second (e.g., 1 tap for 1Hz). Then post treatment RMSE minus baseline RMSE will determine a delta RMSE. A higher RMSE signifies greater error. For the delta measure, it is expected, lower scores reflect greater improvement on the task.	Baseline and At-home sessions (10 minutes/day), up to 23 days
Change in At-home Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 4Hz Speed	Accuracy at baseline will be compared to that of final assessment, which will take place before and after the 3-week at-home practice sessions, respectively. The delta measure will indicate the magnitude of tapping accuracy improvements. Groups will be compared to examine differences in delta as a function of practice condition (tapping only or imagery plus tapping). RMSE (root mean squared error) is the measure for both the baseline and post-treatment behavioral tasks. RMSE will be based on the actual number of taps per second relative to the expected number of taps per second (e.g., 4 taps for 4Hz). Then post treatment RMSE minus baseline RMSE will determine a delta RMSE. A higher RMSE signifies greater error. For the delta measure, it is expected, lower scores reflect greater improvement on the task.	Baseline and At-home sessions (10 minutes/day), up to 23 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient	This will assess the correlation between MRI Blood Oxygen Level Dependence (BOLD) during imagery and finger tapping accuracy improvement (pre- vs. post- neurofeedback training) by a correlation coefficient. The correlation coefficient ranging from -1 to 1, where the closer the coefficient is to -1 indicates a negative association and the closer the coefficient is to 1 indicates a strong positive association.	MRI duration, up to 1 hour
The Correlation Between MRI BOLD and Finger Tapping Accuracy to a Flashing Cue at 4Hz as Assessed by a Correlation Coefficient	This will assess the correlation between MRI Blood Oxygen Level Dependence (BOLD) during imagery and finger tapping accuracy improvement (pre- vs. post- neurofeedback training) by a correlation coefficient. The correlation coefficient ranging from -1 to 1, where the closer the coefficient is to -1 indicates a negative association and the closer the coefficient is to 1 indicates a strong positive association.	MRI duration, up to 1 hour
The Correlation Between the KVIQ and Imagery Accuracy of the Flashing Cross on the MRI Task as Assessed by a Correlation Coefficient	The Kinesthetic and Visual Imagery Questionnaire (KVIQ), overall score ranging from 0-100, where higher scores reflect more vivid imagery) will assess imagery vividness. This will be correlated with the image accuracy measures described in Secondary Outcome Measure 5. The correlation coefficient ranging from -1 to 1, where the closer the coefficient is to -1 indicates a negative association and the closer the coefficient is to 1 indicates a strong positive association.	Up to 1.5 hours
The Correlation Between the ICARS and Imagery Accuracy Accuracy of the Flashing Cross on the MRI Task as Assessed by a Correlation Coefficient	The International Cooperative Ataxia Rating Scale (ICARS), overall score ranging from 0-100, where higher scores indicate more severe neurological impairment) will assess neurological impairments. This will be correlated with image accuracy measures described in 'Secondary Outcome Measure 5. The correlation coefficient ranging from -1 to 1, where the closer the coefficient is to -1 indicates a negative association and the closer the coefficient is to 1 indicates a strong positive association.	Up to 1.5 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Virginia Polytechnic Institute and State University
• Investigators: Principal Investigator: Cherie Marvel, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Actual): January 22, 2024
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Balance; Gait; Movement Disorders; Neurodegenerative Diseases; Cerebellar Ataxia; Cerebellum; Spinocerebellar Ataxias; Cerebellar Diseases
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Dyskinesias; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations
• Other Study ID Numbers: IRB00300264; R21NS125546 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: Access to trial individual participant data (IPD) can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact cmarvel1@jhmi.edu.
• 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: No