Dysfunction in Parkinson’s: Tracing the Neural Connections in Peak-Dose Dyskinesia

Published on August 2, 2022

Imagine the brain as a web of connections, where different regions communicate to perform various tasks. In Parkinson’s disease (PD), the cerebellum, particularly the cerebellar dentate nucleus (DN), is implicated in causing involuntary muscle movements known as peak-dose dyskinesia. However, the exact neural mechanism behind this remains unclear. To shed light on this phenomenon, researchers conducted MRI scans on peak-dose dyskinetic PD patients, non-dyskinetic PD patients, and healthy controls. They analyzed the functional connectivity (FC) patterns of the DN and observed that dyskinetic PD patients had heightened connectivity between the DN and other brain regions, such as the putamen, paracentral lobule, postcentral gyrus, supplementary motor area, and ipsilateral cerebellum lobule VIII. Interestingly, no changes were found in gray matter volume. The study also identified a positive correlation between the strength of DN-putamen connectivity and the severity of dyskinesia symptoms. These findings suggest that disrupted connectivity between the DN and key motor control areas may contribute to peak-dose dyskinesia in PD. To delve deeper into this research, check out the full article!

The cerebellum is associated with the emergence of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD), yet the neural mechanism remains obscure. Our aim was to ascertain the role of functional connectivity (FC) patterns of the cerebellar dentate nucleus (DN) in the pathogenesis of peak-dose dyskinesia in PD. Twenty-three peak-dose dyskinetic PD patients, 27 non-dyskinetic PD patients, and 36 healthy controls (HCs) were enrolled and underwent T1-weighted and resting-state functional magnetic resonance imaging (rs-fMRI) scans after dopaminergic medication intake. We selected left and right DN as the regions of interest and then employed voxel-wise FC analysis and voxel-based morphometry analysis (VBM). The correlations between the altered FC pattern and clinical scores were also examined. Finally, receiver operating characteristic (ROC) curve analysis was performed to assess the potential of DN FC measures as a feature of peak-dose dyskinesia in PD. Dyskinetic PD patients showed excessively increased FC between the left DN and right putamen compared with the non-dyskinetic. When compared with controls, dyskinetic PD patients mainly exhibited increased FC between left DN and bilateral putamen, left paracentral lobule, right postcentral gyrus, and supplementary motor area. Additionally, non-dyskinetic PD patients displayed increased FC between left DN and left precentral gyrus and right paracentral lobule compared with controls. Meanwhile, increased FC between DN (left/right) and ipsilateral cerebellum lobule VIII was observed in both PD subgroups. However, no corresponding alteration in gray matter volume (GMV) was found. Further, a positive correlation between the z-FC values of left DN-right putamen and the Unified Dyskinesia Rating Scale (UDysRS) was confirmed in dyskinetic PD patients. Notably, ROC curve analyses revealed that the z-FC values of left DN-right putamen could be a potential neuroimaging feature identifying dyskinetic PD patients. Our findings demonstrated that the excessively strengthened connectivity of DN-putamen might contribute to the pathophysiological mechanisms of peak-dose dyskinesia in PD.

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