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

Summary

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.

Eligibility

PD PATIENTS:

Inclusion Criteria:

* 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.
* Signed informed consent.

Exclusion Criteria:

* 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 receiving advanced PD treatment such as duodopa pump or apomorphine pen
* Regular intake of antipsychotics and GABAergic medications (such as pregabalin and gabapentine).
* Severe depression (MDI score \> 29).
* Refuse to be informed about new health-related findings that might appear through participation.

HEALTHY CONTROLS:

Inclusion criteria:

* At least 35 years of age.
* Signed informed consent.

Exclusion criteria:

* Female participants of childbearing age must not be pregnant, and they must use contraception.
* Breastfeeding.
* History of neurologic or psychiatric disease other than depression.
* Claustrophobia, pacemakers, implanted electronic devices, metal in the body, or other contraindications for MR scans.
* Regular intake of antipsychotics and GABAergic medications (such as pregabalin and gabapentine).
* Severe depression (MDI score \> 29).
* Refuse to be informed about new health-related information and accidental health-related findings that might appear through participation.

Conditions4

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