FMRI-neurofeedback in Parkinson's Disease

NCT06582355 | Recruiting

• 1 other identifier: NL86308.068.24
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 2

Brief Summary

Rationale: Current treatment of patients with Parkinson's disease (PD) is mainly based on the modulation of neural activity in the motor circuits of the basal ganglia and cerebral cortex by either drug intervention (dopamine replacement therapy or dopaminergic medication) or deep brain stimulation (DBS). However, many Parkinson patients have an insufficient (long-term) response to medical treatments, and DBS is an invasive procedure with resource implications and potential side effects. Moreover, not all patients are eligible for DBS. Therefore, new ways of administering neuromodulation are needed. A potential avenue may be self-regulation of brain circuits through neurofeedback. Self-regulation of motor circuits through mental imagery and neurofeedback using real-time functional MRI (fMRI) signals has already been shown to be feasible, and there are also preliminary data on clinical benefits of such self-regulation training. We here aim to use the non-invasive fMRI-neurofeedback method to train patients in the regulation of brain circuits that are implicated in successful drug treatment and/or DBS. Objective: To investigate brain mechanisms and efficacy of an fMRI-neurofeedback protocol that targets the brain's motor circuits through the basal ganglia. Study design: Randomised controlled trial Study population: Patients with Parkinson's disease Investigation: In the experimental group, fMRI-neurofeedback will be administered in 4 separate sessions of about 2 hours each over approximately one month. The MRI measurement in each session will be approximately 60 minutes long and include upregulation training of brain activity in specific target areas by mental imagery. The fMRI signals are processed such that the patients get visual feedback about the success of the upregulation. In addition, patients are asked to practice the self-regulation strategies on a daily basis at home between the neurofeedback sessions. The control intervention will consist of mental imagery without neurofeedback. Main study parameters/endpoints: Post-interventional improvement of motor symptoms of PD as assessed by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor scale in the on-medication state. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This is a low-risk study where the main burden is participation time and MRI scans.

Conditions

Parkinson Disease

Keywords

Parkinson Disease; Neurofeedback; fMRI

Outcome Measures

Primary Outcomes (1)

• MDS-UPDRS (Unified Parkinson's Disease Rating Scale)

  Pre versus Post-interventional change in the MDS-UPDRS (Unified Parkinson's Disease Rating Scale) motor scale will be compared using t statistics. The MDS-UPDRS contains 65 scores, each with a range from 0 (no impairment) to 4 (severe impairment). The total scale ranges between 0 - 260, with 0 indicating no impairment and 260 indicating the highest level of impairment. As primary outcome measure we will use Part III: Motor Examination, which has 33 scores. The measurement at the last MRI session will be the primary endpoint.

  After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session)

Secondary Outcomes (4)

• Performance of Putamen neurofeedback training (fMRI analysis)

  Measurements will be recorded at each MRI session (approx. 1 week intervals after screening and inclusion)

• Whole brain activation pattern changes (fMRI analysis)

  Measurements will be recorded at each MRI session (approx. 1 week intervals after screening and inclusion)

• Neurofeedback training effects on non-motor symptoms

  After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session)

• Correlation between NF success and distal finger tapping test (behavioral measure)

  After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session)

Other Outcomes (1)

• Neurofeedback training effects on motor symptoms and experiences

  After screening, after the last MRI session (approx. 5 weeks after screening) and at follow up session (approx. 4 weeks after final MRI session)

Study Arms (2)

Neurofeedback

EXPERIMENTAL

Four weekly MRI sessions where they will learn to upregulate the activity of the putamen during motor imagery via fMRI neurofeedback.

Other: Neurofeedback

Kinesthetic imagery

ACTIVE COMPARATOR

Four weekly MRI sessions with motor imagery without fMRI neurofeedback.

Other: Kinesthetic imagery

Interventions

Neurofeedback OTHER

The participants will be instructed to use cognitive strategies to upregulate (increase) their brain activity in the selected brain region, with the suggestion that motor imagery may be particularly effective, for example, mental imagery of swimming or playing a musical instrument. During the rest blocks, the participants will be instructed to relax. The instructions to start and stop the regulation and rest blocks are visualized on a screen in the scanner, and the brain activity of the putamen will be displayed in real-time using a thermometer bar for visualization.

Neurofeedback

Kinesthetic imagery OTHER

The participants will be instructed to imagine movements during the active blocks. During the rest blocks, the participants will be instructed to relax. The instructions to start and stop the regulation and rest blocks are visualized on a screen in the scanner. No feedback is provided regarding brain activity.

Kinesthetic imagery

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Parkinson's disease.
• Disease stage 1-3 according to the Hoehn and Yahr Scale
• Age: 18 years or more

You may not qualify if:

• History of psychotic disorder, bipolar disorder, or psychotic depression
• Current use of illegal drugs (any in the last four weeks)
• Current excessive alcohol consumption that interferes with daily functioning
• A score on the Montreal Cognitive Assessment (MoCA) below 24/30.
• Any disorder that would interfere with accurate and usable data acquisition.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (2)

Uniklinik Köln

Cologne, Germany

NOT YET RECRUITING

Maastricht University

Maastricht, Netherlands

RECRUITING

Related Publications (23)

• Akram N, Li H, Ben-Joseph A, Budu C, Gallagher DA, Bestwick JP, Schrag A, Noyce AJ, Simonet C. Developing and assessing a new web-based tapping test for measuring distal movement in Parkinson's disease: a Distal Finger Tapping test. Sci Rep. 2022 Jan 10;12(1):386. doi: 10.1038/s41598-021-03563-7.

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• Esmail, S., & Linden, D. E. J. (2014). Neural Networks and Neurofeedback in Parkinson's Disease. NeuroRegulation, 1(3-4), 240-240. https://doi.org/10.15540/nr.1.3-4.240

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MeSH Terms

Conditions

Parkinson Disease

Interventions

Neurofeedback

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Biofeedback, Psychology; Mind-Body Therapies; Complementary Therapies; Therapeutics; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Feedback, Psychological

Study Officials

• David EJ Linden, Prof.

  Maastricht University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David EJ Linden, Prof.

CONTACT

+31 43 3881021; david.linden@maastrichtuniversity.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The outcome assessor will be unaware of which condition the participant is in.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: September 3, 2024
• Study Start: February 10, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 24, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DE (1)