Microstructural and functional alterations of the ventral pallidum are associated with levodopa‐induced dyskinesia in Parkinson's disease

Abstract Background and purpose The ventral pallidum (VP) regulates involuntary movements, but it is unclear whether the VP regulates the abnormal involuntary movements in Parkinson's disease (PD) patients who have levodopa‐induced dyskinesia (LID). To further understand the role of the VP in PD patients with LID (PD‐LID), we explored the structural and functional characteristics of the VP in such patients using multimodal magnetic resonance imaging (MRI). Methods Thirty‐one PD‐LID patients, 39 PD patients without LID (PD‐nLID), and 28 healthy controls (HCs) underwent T1‐weighted MRI, quantitative susceptibility mapping, multi‐shell diffusion MRI, and resting‐state functional MRI (rs‐fMRI). Different measures characterizing the VP were obtained using a region‐of‐interest‐based approach. Results The left VP in the PD‐LID group showed significantly higher intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) compared with the PD‐nLID and HC groups. Rs‐MRI revealed that, compared with the PD‐nLID group, the PD‐LID group in the medication ‘off’ state had higher functional connectivity (FC) between the left VP and the left anterior caudate, left middle frontal gyrus and left precentral gyrus, as well as between the right VP and the right posterior ventral putamen and right mediodorsal thalamus. In addition, the ICVF values of the left VP, the FC between the left VP and the left anterior caudate and left middle frontal gyrus were positively correlated with Unified Dyskinesia Rating Scale scores. Conclusion Our multimodal imaging findings show that the microstructural changes of the VP (i.e., the higher ICVF and IsoVF) and the functional change in the ventral striatum–VP–mediodorsal thalamus–cortex network may be associated with pathophysiological mechanisms of PD‐LID.