Altered functional connectivity of cerebellar dentate nucleus in peak-dose dyskinesia in Parkinson's disease

Heng Zhang; Lina Wang; Caiting Gan; Xingyue Cao; Min Ji; Huimin Sun; Yongsheng Yuan; Kezhong Zhang

doi:10.3389/fnagi.2022.943179

Altered functional connectivity of cerebellar dentate nucleus in peak-dose dyskinesia in Parkinson's disease

Front Aging Neurosci. 2022 Aug 2:14:943179. doi: 10.3389/fnagi.2022.943179. eCollection 2022.

Authors

Heng Zhang¹, Lina Wang¹, Caiting Gan¹, Xingyue Cao¹, Min Ji¹, Huimin Sun¹, Yongsheng Yuan¹, Kezhong Zhang¹

Affiliation

¹ Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract

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.

Keywords: Parkinson’s disease; dentate nucleus; functional connectivity; peak-dose dyskinesia; resting-state functional magnetic resonance imaging; voxel-based morphometry analysis.