The investigators aim is to study neuropsychiatric symptoms and underlying abnormalities in resting-state fMRI in patients with Parkinson's disease (PD) suffering from neuropsychiatric fluctuations, to enhance the understanding of the pathophysiological mechanisms underlying neuropsychiatric symptoms.
Parkinson's disease (PD) is primarily classified and known as a movement disorder characterized by tremor, bradykinesia and rigidity. However, clinical examination and research have shown that PD extensively affects other systems as well, giving rise to non-motor symptoms (NMS) such as anxiety, sleep disorders, apathy, depression, cognitive impairment, and hallucinations. These non-motor fluctuations (NMF) represent a main source of disability in PD and among those, neuropsychiatric fluctuations are the most frequent. During the dopaminergic OFF-drug state anxiety, apathy, and depression are common, whereas during the dopaminergic ON-drug state euphoria, well-being, impulse control disorders (ICD) and other behavioral addictions, mania, and psychosis might occur. Despite the severe consequences associated with dopaminergic modulation, the understanding of the pathophysiological mechanisms of neuropsychiatric symptoms is still limited and better detection and more effective treatments are needed. Fluctuating PD is a very powerful model allowing to study opposite psychiatric states intra-individually in both levodopa dopaminergic ON- and OFF-drug state, allowing to abstract many interpersonal variables. Neurotechnology and advanced neuroimaging techniques can improve the understanding of the neural basis and brain mechanisms of specific neuropsychiatric symptoms in PD. In particular, dynamic functional connectivity (FC) analysis characterizes functional abnormalities from resting state (rs)-fMRI not only in terms of brain activations, but also of whole-brain functional networks and the transitions between maps of activations. The temporal evolution of these networks, assessed with dynamic FC approaches, has recently shown to be relevant in several clinical contexts. Therefore, the investigators long-term goal is to identify specific resting-state signatures/biomarkers for the individual neuropsychiatric PD symptoms related to disease in dopaminergic OFF-drug state (depression, anxiety, apathy, fatigue, shame, bradyphrenia) and to dopaminergic treatment in dopaminergic ON-drug state (mania, impulse control disorders, hallucinations, psychosis, creative thinking), which might be used in the future as a proxy for the measurement of neuropsychiatric symptoms/fluctuations and thus to assess the effectiveness of specific therapies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
23
Dopaminergic OFF-drug state: Overnight withdrawal of dopaminergic antiparkinsonian drugs during visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized.
Dopaminergic ON-drug state: Patient will be evaluated in his/her regular treatment in dopaminergic ON-drug state at visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized.
University Hospital Inselspital, Berne
Bern, Switzerland
EPFL Campus Biotech
Geneva, Switzerland
EPFL Institute of Bioengineering
Geneva, Switzerland
University Hospital Geneva (HUG)
Geneva, Switzerland
Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations
Score on the Neuropsychiatric Fluctuations Scale (NFS)
Time frame: ≤ 6 weeks
Correlation of functional connectivity abnormalities with shame
Score on the Shame Visual Analogic Scale
Time frame: ≤ 6 weeks
Correlation of functional connectivity abnormalities with hallucinations
Score on robot-induced presence hallucination (PH) ratings
Time frame: ≤ 6 weeks
Correlation of functional connectivity abnormalities with bradyphrenia
Score on the Bradyphrenia Scale
Time frame: ≤ 6 weeks
Correlation of functional connectivity abnormalities with creativity
Score on the Creative Thinking Scale
Time frame: ≤ 6 weeks
The role of dopamine on hallucinations
Measurement of the influence of dopamine on hallucinations using the robot-induced presence hallucination (PH) ratings. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more hallucinations are experienced by patients.
Time frame: ≤ 6 weeks
The role of dopamine on creativity
Measurement of the influence of dopamine on the Creative Thinking Scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more creative the patients are.
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Time frame: ≤ 6 weeks
The role of dopamine on shame
Measurement of the influence of dopamine on the Shame Visual Analogic Scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more shame patients feel.
Time frame: ≤ 6 weeks
The role of dopamine on bradyphrenia
Measurement of the influence of dopamine on the bradyphrenia scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more bradyphrenic the patients are.
Time frame: ≤ 6 weeks