Parkinson Disease
Conditions
Brief summary
Effect of Mental Imagery Training on Brain Plasticity and Motor Function in Individuals with Parkinson's Disease: A functional MRI investigation.
Detailed description
This project will examine the effect of functional MRI-based neurofeedback on brain plasticity and motor performance in patients with Parkinson's Disease (PD).
Interventions
OTHERPD neurofeedback
PD-neurofeedback subjects will practice motor imagery in the MRI scanner and receive neurofeedback on their performance. There will be a total of 10-12 neurofeedback sessions on two separate days. Subjects will continue practicing motor imagery at home every day throughout the study period for 4-6 weeks.
OTHERPD control
PD-control subjects will practice visual imagery (e.g., of scenery, objects, etc., but not of movement) in the MRI scanner and will not receive neurofeedback on their performance. Subjects will continue practicing visual imagery at home every day throughout the study period for 4-6 weeks.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
double blinded
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of idiopathic PD defined according to the UK Brain Bank diagnostic criteria and on a stable dopaminergic medication regimen will be included.
Exclusion criteria
* Age \< 40 years * Non-English speaking * Pregnancy * Breastfeeding * Excessive alcohol consumption (\> 7 drinks per week for women, \> 14 drinks per week for men) or substance use * History of a neurological disorder such as a brain tumor, stroke, central nervous system infection, multiple sclerosis, movement disorder (other than PD), or seizures * History of schizophrenia, bipolar disorder, attention deficit disorder, or obsessive compulsive disorder * History of head injury with loss of consciousness * Metallic surgical implants or traumatically implanted metallic foreign bodies * Inability to lie flat for about an hour * Discomfort being in small, enclosed spaces * Dementia (Montreal Cognitive Assessment score \< 21) * Depression (Beck Depression Inventory-II score \> 19) * Hoehn & Yahr stage \> 3 (i.e., able to stand and walk, but not fully independent) * Focal neurological findings on exam that suggest cerebral pathology other than that associated with parkinsonism * Motor symptoms that could potentially introduce too much motion artifact in the imaging data (e.g., MDS-UPDRS resting tremor score \> 1 in limbs, head/chin tremor, or dyskinesia by history or exam).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Right Insula-dorsomedial Frontal Cortex Functional Connectivity Strength. | 4-6 weeks | The functional connectivity strength between the subjects' right insula and dorsomedial frontal cortex will be measured at baseline and post-intervention as each group of subjects engages in their respective imagery tasks. Functional connectivity will be measured as the correlation value between the functional MRI signal time courses obtained from these two brain regions. |
| Change in Resting-state Functional Connectivity Between the Right Insula and Dorsomedial Frontal Cortex. | 4-6 weeks | We will obtain resting-state functional MRI scans from the PD-neurofeedback and PD-control groups at baseline and post-intervention to examine the changes in intrinsic functional connectivity between the right insula and dorsomedial frontal cortex. Functional connectivity will be measured as the correlation value between the functional MRI signal time courses obtained from these two brain regions. |
| Change in Motor Impairment | Baseline and 4-6 weeks | We will administer the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor exam) at baseline and post-intervention to the PD-neurofeedback and PD-control groups to measure the change in motor impairment. The MDS-UPDRS part III is a subscale that provides an objective assessment of motor impairment. The scores range between 0-132. Higher scores indicate more severe impairment. |
| Change in Motor Function | Baseline and 4-6 weeks | We will administer standard motor function tests (e.g., timed up and go, 5 times sit-to-stand, 360-degree turn) at baseline and post-intervention to the PD-neurofeedback and PD-control groups to measure the change in motor function. The performance score on these tests is the time to complete the motor tasks. Shorter time indicates better performance. The motor function tests measure movement speed. Timed up and go test measures (seconds) how fast one can stand up from a chair, walk 3 meters, turn, walk back to the chair and sit down again. Five times sit-to-stand test measures (seconds) how fast one can stand up from a chair with arms crossed across the chest and sit back again 5 times in a row. 360-degree turn test measures (seconds) how fast one can turn around their own axis clockwise and counterclockwise. The composite motor function score is the sum of the durations (seconds) of all three tests. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Task-based Functional Connectivity | 1 day | In a group of PD patients who will not receive any intervention, we will collect functional MRI data during a mental imagery task with both motor and visual imagery components to investigate the functional connectivity between the motor and visual networks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With PD Neurofeedback Training Patients will receive neurofeedback training.
PD neurofeedback: PD-neurofeedback subjects will practice motor imagery in the MRI scanner and receive neurofeedback on their performance. There will be a total of 10-12 neurofeedback sessions on two separate days. Subjects will continue practicing motor imagery at home every day throughout the study period for 4-6 weeks. | 22 |
| Patients With PD Control Patients will not receive neurofeedback training.
PD control: PD-control subjects will practice visual imagery (e.g., of scenery, objects, etc., but not of movement) in the MRI scanner and will not receive neurofeedback on their performance. Subjects will continue practicing visual imagery at home every day throughout the study period for 4-6 weeks. | 22 |
| Patients With PD Patients perform mental imagery (motor and visual aspects combined) in the MRI scanner without neurofeedback training. This was a small pilot arm with no intervention conducted after the completion of the study. | 9 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | COVID-19 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | Patients With PD Neurofeedback Training | Total | Patients With PD | Patients With PD Control |
|---|---|---|---|---|
| Age, Continuous | 66.2 years STANDARD_DEVIATION 8.1 | 66.2 years STANDARD_DEVIATION 8 | 67.4 years STANDARD_DEVIATION 6.1 | 65.7 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 51 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 52 Participants | 9 Participants | 21 Participants |
| Region of Enrollment United States | 22 participants | 53 participants | 9 participants | 22 participants |
| Sex: Female, Male Female | 10 Participants | 27 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 12 Participants | 26 Participants | 2 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 28 | 0 / 9 |
| other Total, other adverse events | 0 / 26 | 0 / 28 | 0 / 9 |
| serious Total, serious adverse events | 0 / 26 | 0 / 28 | 0 / 9 |
Outcome results
Primary
Change in Motor Function
We will administer standard motor function tests (e.g., timed up and go, 5 times sit-to-stand, 360-degree turn) at baseline and post-intervention to the PD-neurofeedback and PD-control groups to measure the change in motor function. The performance score on these tests is the time to complete the motor tasks. Shorter time indicates better performance. The motor function tests measure movement speed. Timed up and go test measures (seconds) how fast one can stand up from a chair, walk 3 meters, turn, walk back to the chair and sit down again. Five times sit-to-stand test measures (seconds) how fast one can stand up from a chair with arms crossed across the chest and sit back again 5 times in a row. 360-degree turn test measures (seconds) how fast one can turn around their own axis clockwise and counterclockwise. The composite motor function score is the sum of the durations (seconds) of all three tests.
Time frame: Baseline and 4-6 weeks
Population: Complete case analyses and participants in the pilot PD arm did not have these data collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With PD Neurofeedback Training | Change in Motor Function | Pre | 23.7 seconds | Standard Deviation 4.7 |
| Patients With PD Neurofeedback Training | Change in Motor Function | Post | 22.3 seconds | Standard Deviation 5.1 |
| Patients With PD Control | Change in Motor Function | Pre | 24.4 seconds | Standard Deviation 4.9 |
| Patients With PD Control | Change in Motor Function | Post | 24.1 seconds | Standard Deviation 5.2 |
Comparison: Testing for main effects (group), time effect and the interaction of group and time.p-value: 0.026ANOVA
Primary
Change in Motor Impairment
We will administer the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor exam) at baseline and post-intervention to the PD-neurofeedback and PD-control groups to measure the change in motor impairment. The MDS-UPDRS part III is a subscale that provides an objective assessment of motor impairment. The scores range between 0-132. Higher scores indicate more severe impairment.
Time frame: Baseline and 4-6 weeks
Population: Complete case analyses and participants in the pilot PD arm did not have these data collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With PD Neurofeedback Training | Change in Motor Impairment | Post | 31.3 score on a scale | Standard Deviation 9.8 |
| Patients With PD Neurofeedback Training | Change in Motor Impairment | Pre | 32.3 score on a scale | Standard Deviation 8.1 |
| Patients With PD Control | Change in Motor Impairment | Pre | 34.5 score on a scale | Standard Deviation 9.6 |
| Patients With PD Control | Change in Motor Impairment | Post | 35.1 score on a scale | Standard Deviation 10.8 |
Comparison: Testing for main effects (group), time effect and the interaction of group and time.p-value: >0.05ANOVA
Primary
Change in Resting-state Functional Connectivity Between the Right Insula and Dorsomedial Frontal Cortex.
We will obtain resting-state functional MRI scans from the PD-neurofeedback and PD-control groups at baseline and post-intervention to examine the changes in intrinsic functional connectivity between the right insula and dorsomedial frontal cortex. Functional connectivity will be measured as the correlation value between the functional MRI signal time courses obtained from these two brain regions.
Time frame: 4-6 weeks
Population: Complete case analyses and participants in the pilot PD arm did not have these data collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With PD Neurofeedback Training | Change in Resting-state Functional Connectivity Between the Right Insula and Dorsomedial Frontal Cortex. | -2.9 percent change from baseline | Standard Error 43.7 |
| Patients With PD Control | Change in Resting-state Functional Connectivity Between the Right Insula and Dorsomedial Frontal Cortex. | 74.2 percent change from baseline | Standard Error 58.8 |
p-value: 0.481Wilcoxon (Mann-Whitney)
Primary
Change in Right Insula-dorsomedial Frontal Cortex Functional Connectivity Strength.
The functional connectivity strength between the subjects' right insula and dorsomedial frontal cortex will be measured at baseline and post-intervention as each group of subjects engages in their respective imagery tasks. Functional connectivity will be measured as the correlation value between the functional MRI signal time courses obtained from these two brain regions.
Time frame: 4-6 weeks
Population: Complete case analyses and participants in the pilot PD arm did not have these data collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With PD Neurofeedback Training | Change in Right Insula-dorsomedial Frontal Cortex Functional Connectivity Strength. | 93.2 percent change from baseline | Standard Error 84.1 |
| Patients With PD Control | Change in Right Insula-dorsomedial Frontal Cortex Functional Connectivity Strength. | 97.8 percent change from baseline | Standard Error 106.6 |
p-value: 0.981Wilcoxon (Mann-Whitney)
Other Pre-specified
Task-based Functional Connectivity
In a group of PD patients who will not receive any intervention, we will collect functional MRI data during a mental imagery task with both motor and visual imagery components to investigate the functional connectivity between the motor and visual networks.
Time frame: 1 day