Trial Outcomes & Findings for Using Real-time fMRI Neurofeedback and Motor Imagery to Enhance Motor Timing and Precision in Cerebellar Ataxia (NCT NCT05436262)

Last Updated: 2025-01-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

21 participants

Primary outcome timeframe

Baseline and MRI duration, up to 1 hour

Results posted on

2025-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Pre-Randomization: fMRI Neurofeedback 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Tapping Only (Control Group) 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.	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
Pre-Randomization STARTED	21	0	0
Pre-Randomization COMPLETED	20	0	0
Pre-Randomization NOT COMPLETED	1	0	0
Randomization STARTED	0	11	9
Randomization COMPLETED	0	10	9
Randomization NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Pre-Randomization: fMRI Neurofeedback 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Tapping Only (Control Group) 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.	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
Pre-Randomization Withdrawal by Subject	1	0	0
Randomization Withdrawal by Subject	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Real Time Neurofeedback With Task With At-home Practice Sessions n=21 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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. Group 2: Imagery on 13 daily sessions, and overt tapping on 4 sessions.
Age, Continuous	58.31 years STANDARD_DEVIATION 11.69 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 Participants n=5 Participants
Region of Enrollment United Kingdom	1 Participants n=5 Participants
International Cooperative Ataxia Rating Scale (ICARS)	35.43 units on a scale STANDARD_DEVIATION 19.36 • n=5 Participants
Kinesthetic and Visual Imagery Questionnaire (KVIQ)	38.00 units on a scale STANDARD_DEVIATION 9.24 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and MRI duration, up to 1 hour

Population: One person withdrew from the MRI portion and did not complete the task. Four additional participants were unable to complete the functional MRI task as instructed, confirmed by post-experimental questionnaires. Because these people were presumably using strategies that were not of interest to the research question, their data was excluded from analysis.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=16 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
Change in Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 1Hz Speed	.00141488 taps per second Standard Deviation .007294434	—

PRIMARY outcome

Timeframe: Baseline and MRI duration, up to 1 hour

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.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=16 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
Change in Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 4Hz Speed	.00165387 taps per second Standard Deviation .010581808	—

PRIMARY outcome

Timeframe: Baseline and At-home sessions (10 minutes/day), up to 23 days

Population: Four people did not complete the MRI component as instructed, and one person in the tapping only (control group) condition did not complete the final 7 at-home exercise sessions. These 5 people were excluded from at-home data analysis (a total of 3 excluded from Tapping and 2 excluded from Imagery).

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.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=8 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) n=7 Participants 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.
Change in At-home Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 1Hz Speed	.392919831 taps per second Standard Deviation .6227685278	.200339199 taps per second Standard Deviation .3242518927

PRIMARY outcome

Timeframe: Baseline and At-home sessions (10 minutes/day), up to 23 days

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.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=8 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) n=7 Participants 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.
Change in At-home Overt Tapping Accuracy as Assessed by Finger Tapping to a Flashing Cue at 4Hz Speed	.35613192 taps per second Standard Deviation .7481023854	.067492801 taps per second Standard Deviation .5086197309

SECONDARY outcome

Timeframe: MRI duration, up to 1 hour

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.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=16 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient Left Crus II cerebellum	.850 correlation coefficient	—
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient Right Posterior Insula	.861 correlation coefficient	—
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient Right Inferior Frontal Gyrus	.838 correlation coefficient	—
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient Left Posterior Insula	.842 correlation coefficient	—
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient Left Internal Capsule	.884 correlation coefficient	—
The Correlation Between MRI BOLD During Imagery and Finger Tapping Accuracy Improvements to a Flashing Cue at 1Hz as Assessed by a Correlation Coefficient Right Ventral Caudate	.850 correlation coefficient	—

SECONDARY outcome

Timeframe: MRI duration, up to 1 hour

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=16 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
The Correlation Between MRI BOLD and Finger Tapping Accuracy to a Flashing Cue at 4Hz as Assessed by a Correlation Coefficient	.688 correlation coefficient	—

SECONDARY outcome

Timeframe: Up to 1.5 hours

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.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=16 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
The Correlation Between the KVIQ and Imagery Accuracy of the Flashing Cross on the MRI Task as Assessed by a Correlation Coefficient	.953 correlation coefficient	—

SECONDARY outcome

Timeframe: Up to 1.5 hours

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.

Outcome measures

Outcome measures
Measure	Pre-Randomization: fMRI Neurofeedback n=16 Participants 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: 1. Overt finger tapping in time with a flashing cue. 2. 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).	Randomization: Homework Sessions With Imagery Only (Intervention Group) 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.
The Correlation Between the ICARS and Imagery Accuracy Accuracy of the Flashing Cross on the MRI Task as Assessed by a Correlation Coefficient	-.263 correlation coefficient	—

Adverse Events

Pre-Randomization: fMRI Neurofeedback

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

fMRI Neurofeedback and Homework Sessions With Tapping (Control Group)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

fMRI Neurofeedback and Homework Sessions With Imagery (Intervention Group)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Cherie Marvel

Johns Hopkins University

Phone: 410-387-8510

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place