Parkinson Disease
Conditions
Keywords
Neuropsychiatric fluctuations, Creativity, Shame, Embarrassment, Non-motor symptoms, Hallucinations, Bradyphrenia
Brief summary
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.
Detailed description
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.
Interventions
OTHERDopaminergic OFF-drug state
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.
OTHERDopaminergic ON-drug state
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.
Sponsors
University Hospital, Geneva
Ecole Polytechnique Fédérale de Lausanne
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults above 18 years old * Male or female * Diagnosed with Parkinson's disease * Able to understand instructions, neuropsychological tests and provide written informed consent * Able to understand the locally used language of the experimental site and speak fluently * Presence of neuropsychiatric fluctuations, defined as the sum ≥ 3 of items included in the Ardouin Scale of Behaviour in Parkinson's Disease (ASBPD) part 2
Exclusion criteria
* Structural brain disease other than Parkinson's disease * Substance abuse and/or dependence (other than DRT) * Ongoing depression with suicidal ideation * Severe tremors/dyskinesia/ interfering with MRI performance * Participating in a pharmacological study * Inability to provide informed consent (legal guardianship) * MRI contraindications * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of functional connectivity abnormalities with creativity | ≤ 6 weeks | Score on the Creative Thinking Scale |
| Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations | ≤ 6 weeks | Score on the Neuropsychiatric Fluctuations Scale (NFS) |
| Correlation of functional connectivity abnormalities with shame | ≤ 6 weeks | Score on the Shame Visual Analogic Scale |
| Correlation of functional connectivity abnormalities with hallucinations | ≤ 6 weeks | Score on robot-induced presence hallucination (PH) ratings |
| Correlation of functional connectivity abnormalities with bradyphrenia | ≤ 6 weeks | Score on the Bradyphrenia Scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The role of dopamine on creativity | ≤ 6 weeks | 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. |
| The role of dopamine on shame | ≤ 6 weeks | 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. |
| The role of dopamine on bradyphrenia | ≤ 6 weeks | 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. |
| The role of dopamine on hallucinations | ≤ 6 weeks | 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. |
Countries
Switzerland
Outcome results
None listed