Cerebral Contributions to Symptom Progression in PD

Striatal dopamine depletion leads to dysfunction in the cortico-striatal motor circuit and is an important contributor to motor symptoms in Parkinson's disease (PD). However, dopamine depletion in striatal motor regions is already severe at symptom onset and tends to correlate poorly with progressive worsening. This indicates that the severity of motor symptoms in PD may not be solely dependent on basal ganglia dysfunction. In PD, the deleterious effect of basal ganglia dysfunction on motor control may be partially counteracted by neuroplasticity and the compensatory recruitment of parieto-premotor areas of cortex that drive movement based on sensory cueing and goal-directed cognitive control. The efficacy of cortical compensation could therefore be a core determinant of motor impairment in PD.

This study utilizes longitudinal clinical and brain imaging data from early-stage PD patients included in the Personalized Parkinson Project (ClinicalTrials.gov Identifier: NCT03364894) to test whether motor symptom severity and progression can be predicted by action selection-related brain activity in parieto-premotor cortex, basal ganglia, or a combination of both.

Additional control analyses will be performed to investigate the effects of disease and medication on action selection-related brain activity. Action selection-related brain activity will be compared between PD patients and a cohort of healthy controls to assess the effect of disease (PD vs Healthy). Effects of medication (on vs. off) on action selection-related brain activity will be investigated through within-subject comparisons in subset of PD patients who underwent functional brain imaging in both on- and off-medicated states.

Inclusion criteria

(patients):

• Subject is included in the Personalized Parkinson Project and has already participated in all baseline measurements (this means that inclusion and exclusion criteria of the Personalized Parkinson Project have already been fulfilled)
• Subject has completed the Informed Consent Form, as approved by the Ethics Committee

Exclusion criteria

(patients):

• Subject is not taking dopaminergic medication

Inclusion criteria

(healthy controls):

• Subject is at least 40 years old
• Subject can read and understand Dutch
• Subject has completed the Informed Consent Form, as approved by the Ethics Committee
• Subject is willing, competent, and able to comply with all aspects of the protocol, including follow-up schedule.

Exclusion criteria

(healthy controls):

• Subject has no co-morbidities that would negatively influence the interpretability of results from a comparison with PD patients (e.g. other neurodegenerative diseases or mental health disorders)