Funded Studies
Study Rationale:
Parkinson's disease (PD) is a progressive disorder, but it is unclear what causes the gradual worsening of the symptoms over the years. It is also unknown why in some cases the disease progresses very rapidly while in others it has a mild course. Here we aim to investigate which brain mechanisms are involved in the gradual worsening of motor symptoms in PD. More specifically, we aim to disentangle the contribution of two potential brain mechanisms: the progressive loss of dopamine, which causes dysfunction of the basal ganglia (the brain region affected the most in PD), and the inability of other brain regions not affected by Parkinson's to compensate for basal ganglia dysfunction.
Hypothesis:
We hypothesize that the speed of Parkinson's disease progression depends on the brain's ability to compensate for the shortage of dopamine.
Study Design:
We will collect brain scans using functional magnetic resonance imaging (MRI), a technique for studying brain regions involved in a specific task. We will collect the scans at two time points with an interval of two years from 325 people with PD. All study participants will perform a motor task in an MRI scanner, which will allow us to measure brain activity in the basal ganglia and compensatory brain activity in other brain regions. We will also measure the worsening of motor symptoms during the two-year period using clinical assessment methods. This will allow us to determine whether clinical disease progression is associated with a progressive basal ganglia dysfunction or with a change in the brain's ability to compensate for the dysfunction.
Impact on Diagnosis/Treatment of Parkinson's disease:
This study will demonstrate how compensatory mechanisms, such as neuroplasticity, contribute to worsening of symptoms in Parkinson's disease. This may help us predict an individual course of PD.
Next Steps for Development:
If we confirm our hypothesis that the brain's ability to compensate plays a larger role in shaping disease progression than does the dysfunction of the basal ganglia, then this may cause a paradigm shift in research, re-orienting therapeutic clinical trials from neuroprotection to neuroplasticity.