Multimodal Neuroimaging Reveals Distinct Characteristics of Levodopa-Induced Dyskinesias in de novo Parkinson's Disease Patients.

Levodopa-induced dyskinesia (LID) is a significant treatment complication that affects a substantial proportion of Parkinson’s disease (PD) patients. Our understanding of the neural basis of LID remains limited, partly due to the small sample sizes in existing neuroimaging studies. In this study, we utilized structural MRI data from the Parkinson’s Progression Markers Initiative (PPMI) database, including de novo PD patients (104 non-dyskinetic for at least 3 years after diagnosis and 120 who developed dyskinesia) and 100 age- and sex-matched healthy controls. Additionally, we analyzed resting-state functional MRI data from a subset of these participants to investigate connectivity differences among the groups. Our multimodal MRI analysis revealed significant differences between dyskinetic and non-dyskinetic PD patients across structural and functional domains. While no significant group differences were found in overall brain volumes, dyskinetic patients showed greater cortical thickness in the frontal and sensorimotor cortices. Vertex-based subcortical shape analysis further identified localized surface inflation in the left caudate and left pallidum, along with bilateral pallidal shape alterations in the dyskinetic group. Finally, resting-state functional connectivity analysis revealed stronger connectivity between the putamen, inferior frontal gyrus, and postcentral gyrus in dyskinetic PD patients compared to non-dyskinetics. These findings suggest that specific morphological and functional changes in the cortical-basal ganglia circuitry of de novo PD patients may predispose them to LID over time. Additionally, the altered functional connectivity patterns reinstate the role of the inferior frontal gyrus in the pathophysiology of dyskinesia and suggest that it might be a suitable target for neuromodulatory interventions.