Functional Reorganization of Corticostriatal Connectivity Across the Degree of Nigrostriatal Degeneration in Parkinson Disease.
Level 4 - case-series / case-control
Cross-sectional observational study comparing patients across disease stages and healthy controls using imaging biomarkers.
PubMed 41996661 · doi:10.1212/WNL.0000000000214812
What was done
In a cross-sectional study, 326 patients with Parkinson disease (PD), 29 patients with idiopathic REM sleep behavior disorder (iRBD), and 80 healthy controls (HCs; 40 to determine striatal dopamine depletion baselines and 40 for functional connectivity comparisons) underwent brain resting-state functional MRI, 18F-FP-CIT PET, and Unified Parkinson's Disease Rating Scale motor assessments. Using a sliding window method across a putaminal dopamine decline from 70% to 20%, researchers measured functional connectivity changes from seed regions in the anterior and posterior caudate and putamen on the more and less affected sides.
What was found
On the more affected side, the posterior caudate showed increased functional connectivity with the primary motor cortex and paracentral lobule that emerged before approximately 50% putaminal dopamine depletion, peaked around 50%, and disappeared as caudate dopamine levels abnormally declined. Conversely, the more affected posterior putamen showed reduced connectivity with the superior parietal cortex, precuneus, and cuneus once putaminal dopamine depletion reached approximately 50%, coinciding with linear deterioration in motor symptoms. Functional connectivity between the posterior putamen and motor cortex remained unchanged.
Why it matters
This study defines a distinct phase of corticostriatal functional reorganization, showing transient compensatory connectivity involving the caudate during early dopamine depletion before motor decline accelerates.
Limits
The design is cross-sectional rather than longitudinal, inferring progression across disease stages from a continuous dopamine depletion metric. Abstract does not report exact effect sizes, confidence intervals, or medication state during functional neuroimaging.
Cited by
- supports At clinical manifestation of Parkinson's disease, patients have approximately 40 to 50% substantia nigra cell loss and 60 to 80% striatal dopamine loss.