Optimistic and Pessimistic Dopamine Signals in the Human Brain: a Mapping and Modelling Study in Health and Parkinson's Disease

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.