Mapping optimistic and pessimistic dopamine signals in health and Parkinson's disease

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

We will try to see if people with Parkinson's disease have a different mix of optimistic and pessimistic dopamine signals than healthy people by measuring brain responses during a reward task in an MRI.

Quick facts

• Study type: Observational
• Enrollment: 140 (estimated)
• Ages: 35 Years and up
• Sex: All
• Sponsor: Danish Research Centre for Magnetic Resonance (Academic / other)
• Locations: 1 site (Hvidovre)
• Trial ID: NCT07402928 on ClinicalTrials.gov

What this trial studies

This observational project uses a reward-learning task inside an MRI to measure brain activity in the ventral tegmental area and basal ganglia in people with Parkinson's disease and healthy participants. Researchers will apply computational reinforcement-learning models, including distributional RL concepts, to derive maps of optimistic and pessimistic reward prediction signals. They will compare the distribution and topography of these signals between groups to test whether pessimistic-type signals are selectively reduced in Parkinson's disease. The work combines high-resolution functional imaging with model-based analysis to link cellular-level findings from animal work to human brain function.

Who should consider this trial

Good fit: Ideal candidates are adults aged 35 or older with clinically established or probable akinetic-rigid Parkinson's disease who are on stable antiparkinsonian medication, can undergo MRI, and can give informed consent.

Not a fit: Patients unlikely to benefit include those with advanced device-based PD treatments (e.g., duodopa pump or apomorphine pen), severe depression, other neurologic/psychiatric disorders, regular antipsychotic or certain GABAergic medication use, or contraindications to MRI.

Why it matters

Potential benefit: If successful, the results could clarify why motivation and reward learning are disrupted in Parkinson's and point to new targets or strategies for symptom-specific treatments.

How similar studies have performed: Related distributional reinforcement-learning findings have been demonstrated in mice but mapping optimistic/pessimistic dopamine signals in humans is largely novel and not yet established.

Eligibility criteria

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.

Where this trial is running

Hvidovre

• Danish Research Centre for Magnetic Resonance (DRCMR), Hvidovre Hospital — Hvidovre, Denmark (Recruiting)

Study contacts

• Principal investigator: David Meder, PhD — Danish Research Centre for Magnetic Resonance (DRCMR), Hvidovre Hospital
• Study coordinator: David Meder, PhD

Conditions Healthy; Parkinson; Medication Administration; dopamine; reinforcement learning; distributional reinforcement learning; reward prediction error; reward