Innovative Biomarkers in de Novo Parkinson's Disease

Study Overview
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Brief Summary
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This study aims at identifying potential new and innovative biomarkers in de novo Parkinson's disease patients. New finding will help phenotyping patients since the diagnosis of the disease and potentially also in the preclinical phase.

Detailed Description
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The investigators will use 4 different approaches in parallel: detailed clinical evaluation using the current available validated clinical scales and the Dopamine transporter (DAT) SPECT imaging; anatomical and perfusional brain evaluation using functional MRI; cortical brain mapping and transcranial magnetic stimulation assessment using a robotized approach; emotional responses study using a novel paradigm. These 4 modalities will be assessed at baseline, 1 year and 2 years follow-up. The investigators will integrate these 4 analysis using a mathematical paradigm in order to define specific phenotype of disease and disease progression.

Official Title
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Innovative Biomarkers in de Novo Parkinson's Disease

Conditions
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Parkinson's Disease, Healthy Controls Group - Age and Sex-matched

Intervention / Treatment
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* Procedure: Brain MRI
* Procedure: TMS-EEG
* Behavioral: Behavioral and cognitive battery
* Other: Clinical evaluation and clinical scales


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's disease Asymmetric bradykinesia and/or resting tremor and rigidity since less than 2.5 years ; Hoehn & Yahr ≤ 2/5 ; Montreal cognitive assessment ≥ 26/30 ; Exclusion Criteria: Treatment for Parkinson's disease (except selegiline and rasagiline) Severe visual/retinal pathology revealed during ophthalmological assessment Hyper-sensibility to gadolinium Renal failure Specific MRI contraindication Specific TMS contraindication

Ages Eligible for Study
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Minimum Age: 30 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Parkinson's disease patient<br>Brain functional MRI, robotic TMS + EEG, neuropsychological evaluation, neurological examination for motor and non motor symptoms | Procedure: Brain MRI<br>* 3 Tesla brain MRI for structural and perfusion evaluation, resting state analysis and functional MRI<br>Procedure: TMS-EEG<br>* Transcranial magnetic stimulation (TMS) coupled with electroencephalogram (EEG) study<br>Behavioral: Behavioral and cognitive battery<br>* Emotional, attentional and behavioral assessment using predefine scales and measures<br>Other: Clinical evaluation and clinical scales<br>* Neurological evaluation, ophthalmologic assessement, Montreal cognitive assessment (MoCA), movement disorder society (MDS)- UPDRS<br>|
| Other: Healthy controls<br>Brain functional MRI, robotic TMS + EEG, neuropsychological evaluation, neurological examination | Procedure: Brain MRI<br>* 3 Tesla brain MRI for structural and perfusion evaluation, resting state analysis and functional MRI<br>Procedure: TMS-EEG<br>* Transcranial magnetic stimulation (TMS) coupled with electroencephalogram (EEG) study<br>Behavioral: Behavioral and cognitive battery<br>* Emotional, attentional and behavioral assessment using predefine scales and measures<br>Other: Clinical evaluation and clinical scales<br>* Neurological evaluation, ophthalmologic assessement, Montreal cognitive assessment (MoCA), movement disorder society (MDS)- UPDRS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare cortical excitability differences between subjects | The EEG data after transcranial magnetic stimulation testing will be compared between parkinsonian patients and controls | In a seven months period after inclusion | 
| To compare brain structural differences between subjects | All subjects will have a 3 Tesla brain MRI to collect data concerning anatomy. All data will be compared between patients and controls. Brain MRI study will consist in having the following sequences: T1 and T2, Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR) | In a seven months period after inclusion | 
| To compare brain perfusional differences between subjects | All subjects will have a 3 Tesla brain MRI to collect data concerning perfusion. All data will be compared between patients and controls. Brain MRI study will consist in having the following sequences: Pseudo-Continuous Arterial Spin Labeling (PCASL), T2 with gadolinium, FLAIR | In a seven months period after inclusion | 
| To compare brain connectivity differences between subjects | All subjects will have a 3 Tesla brain MRI to collect data concerning functional connectivity at rest. All data will be compared between patients and controls. Brain MRI study will consist in having the following sequences: Echo planar imaging (EPI) for the blood oxygen level-dependent effect | In a seven months period after inclusion | 
| To compare emotional, attentional and behavior differences between subject | Subjects will be asked to comment on different pictures (if the picture induces pleasure, sorrow or nothing; what would the subjects do). Attentional parameters will be recorded using the Eye tracker. | In a seven months period after inclusion | 
| To compare emotional, attentional and behavior differences between subject with functional MRI | During a functional MRI study, subjects will be asked to comment on different pictures (if the picture induces pleasure, sorrow or nothing; what would the subjects do). Attentional parameters will be recorded using the Eye tracker. | In a seven months period after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Magnetic resonance imaging (MRI), Neuropsychology, Transcranial magnetic stimulation (TMS)