The goal of this observational study is to investigate whether the healthy human brain shows a diversity of optimistic and pessimistic reward signals and whether changes in this distribution in Parkinson's disease (PD) can provide mechanistic insights into the cause of symptoms.
The main hypotheses it aims to test are:
1. As shown in mice, a diversity of optimistic and pessimistic dopamine reward signals exists in the human ventral tegmental area (VTA) and the ventro-rostral basal ganglia circuit. 2. Pessimistic neurons are more severely affected by neurodegeneration in PD.
Researchers will compare the diversity of optimistic and pessimistic dopamine reward signals in patients with PD and healthy participants to see if there is a skewed distribution of optimistic and pessimistic reward signals in PD. Participants will play a task probing reward- and movement related brain activity in an MRI scanner. Researchers will derive functional topographic maps of optimism/pessimism in VTA, substantia nigra pars compacta (SNc), striatum and cortical areas such as the anterior cingulate cortex (ACC).
In sub-study 1, participants will be tested on one study day where patients with PD are tested in the off-medication state (40 control participants, 40 patients with PD).
In sub-study 2, to test whether/how dopaminergic medication affects the distribution of optimism/pessimism, participants will be tested on two study days (30 control participants, 30 patients with PD). Patients with PD are tested one day in the off-medication state, another day in the on-medication state (order counterbalanced between patients with PD). Control participants are tested on two days without medication challenge to test for test-retest effects.
At least 35 years of age.
Clinically established or probable PD according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease
Akinetic-rigid type PD
Stable antiparkinsonian medicine for 4 weeks without major side effects such as dyskinesia or on-off periods.
Female participants of childbearing age must not be pregnant, and they must use contraception.
Breastfeeding.
History of other neurologic or psychiatric disease other than depression.
Claustrophobia, pacemakers, implanted electronic devices, metal in the body, or other contraindications for MR scans.
Patients with PD and healthy volunteers, who are age- and sex-matched to the PD group.
Case-control
Cross-sectional
Not listed
Topographic distribution of the degree of optimism or pessimism
The main outcome measure is the topographic distribution of the degree of optimism or pessimism of each voxel's prediction error signal across the brains' cortical and sub-cortical grey matter. Investigators focus on the dopaminergic midbrain regions VTA/SNc and their main target region, the striatum. In sub-study 1, this distribution will be compared between people with Parkinson's disease and healthy controls. In sub-study 2, the change in distribution between the off- and the on-medication state in patients with PD will be compared to the test-retest change in distribution in control participants.
Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
MDS-UPDRS total score (sum of all 4 sub-scores listed below, range 0-260; higher score = worse outcome) and all four sub-scores. Sub-scores include: Part l subscore: Non-Motor Aspects of Experiences of Daily Living (nM-EDL; range 0-52; higher score = worse outcome); Part ll sub-score: motor experiences of daily living (M-EDL; range 0-52; higher score = worse outcome); Part lll sub-score: motor examination (range 0-132; higher score = worse outcome); Part lV sub-score: motor complications (range 0-24; higher score = worse outcome).
Major Depression Inventory (MDI)
Major Depression Inventory (MDI) total score (range 0-50; higher score = worse outcome)
Montreal Cognitive Assessment (MoCA)
Montreal Cognitive Assessment (MoCA) total score (range 0-30; higher score = better outcome) and sub-scores. Sub-scores include: Visuospatial/executive (range 0-5; higher score = better outcome); Naming (range 0-3; higher score = better outcome); Attention (range 0-6; higher score = better outcome); Language (range 0-3; higher score = better outcome); Abstraction (range 0-2; higher score = better outcome); Delayed recall (range 0-5; higher score = better outcome); Orientation (range 0-6; higher score = better outcome). Additionally, Memory Index Score (range 0-15; higher score = better outcome) is also examined.
Apathy Scale (AS)
Apathy Scale (AS) total score (range 0-42; higher score = worse outcome)
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Danish Research Centre for Magnetic Resonance
Lead sponsor
University Hospital Bispebjerg and Frederiksberg
Collaborator
