Non-invasive Brain Mapping of Movement Facilitation in Parkinson's Disease

Study Overview
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Brief Summary
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Several strategies or contexts help patients with Parkinson's disease to move more quickly or normally, however the brain mechanisms underlying these phenomena are poorly understood. The proposed studies use complimentary brain mapping techniques to understand the brain mechanisms supporting improved movements elicited by external cues. The central hypothesis is that distinct networks are involved in movement improvement depending on characteristics of the facilitating stimulus. Participants will perform movement tasks during recording of brain activity with EEG and MRI. The identified biomarkers may provide targets for future neuromodulation therapies to improve symptoms that are refractory to current treatments, such as freezing of gait.

Detailed Description
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The studies proposed here test the overarching hypothesis that different types of cues (visual targets, rhythmic auditory stimuli and reward incentives) facilitate movement through distinct neuroanatomic circuits and electrophysiological mechanisms, by leveraging known variability in behavioral cueing benefits across patients. Aim 1 is to demonstrate behavioral dissociations between different forms of movement facilitation within patients and relate variability in cueing benefits to integrity of dissociable neuroanatomic circuits as measured by resting state and diffusion tensor magnetic resonance imaging (MRI). Aim 2 is to characterize the electrophysiological correlates of behavioral benefits for the different cue types using electroencephalography (EEG). Patients will perform two computer tasks involving reaching and tapping movements during video recording of movements and electrophysiological recording of brain signals. Experimental manipulations involve different computer stimuli that manipulate the presence or absence of sensory and motivational movement cues. The same experimental manipulations are delivered to all individual subjects. 60 patients with Parkinson's disease and 30 healthy controls will perform the task during recording of brain waves from the scalp (EEG) and return for a second session to record brain activity with MRI. Each of the total of 2 sessions will last about 1.5 hours. Patients may be asked to delay taking their morning Parkinson's disease medications and perform clinical rating scales and questionnaires and undergo a movement disorders neurological exam.

Official Title
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Non-invasive Brain Mapping of Movement Facilitation in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Behavioral: Movement task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Parkinson's disease based on presence of at least 2 cardinal features (tremor, rigidity or bradykinesia) OR healthy adult with no neurologic disease Age > 18 years old Exclusion Criteria: Dementia as indicated by score on Montreal Cognitive Assessment < 19 Active hallucinations or psychosis Contraindications to MRI (metal implant, claustrophobia)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants undergo the same behavioral interventions in which upper extremity movements are made in response to different sensory stimuli.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parkinson disease patients<br>Participants diagnosed with Parkinson's disease | Behavioral: Movement task<br>* Computer task with experimental conditions manipulating sensory and motivation cues for movement.<br>* Other names: Computer task;|
| Active Comparator: Healthy adults<br>Healthy adult age-matched controls | Behavioral: Movement task<br>* Computer task with experimental conditions manipulating sensory and motivation cues for movement.<br>* Other names: Computer task;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EEG recordings | EEG power in the beta band | baseline | 
| BOLD fMRI: functional brain connectivity | Blood oxygen level dependent (BOLD) resting state network activity as a function of behavioral benefits from external cues | up to 4 weeks | 
| Diffusion tractography imaging (MRI): structural brain connectivity | Diffusion tensor fractional anisotropy as a function of behavioral benefits from external cues | up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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movement, external cueing, brain mapping