Levodopa-Induced Dyskinesias Mechanism — Experiment Design

SUMMARY

# Levodopa-Induced Dyskinesias Mechanism — Experiment Design ## Background and Rationale Levodopa-induced dyskinesias (LID) represent a debilitating complication affecting 40-90% of Parkinson's disease patients within 5-10 years of levodopa therapy. While levodopa effectively replaces dopamine in the degenerating nigrostriatal pathway, chronic administration paradoxically generates involuntary hyperkinetic movements that severely impact quality of life. The underlying pathophysiology involves co

METHODOLOGY NOTES

Phase 1 (Months 1-6): Recruit 120 participants across three cohorts (n=40 each): levodopa-naive PD patients, levodopa-treated non-dyskinetic patients (>2 years treatment), and LID patients (UDysRS score >20). Obtain informed consent, medical histories, and standardized assessments (UPDRS, UDysRS, Hoehn-Yahr staging). Phase 2 (Months 7-18): Conduct baseline evaluations including 18F-DOPA and 11C-raclopride PET scans to quantify dopamine synthesis capacity and D2 receptor availability. Perform task-based and resting-state fMRI to assess cortico-striatal connectivity patterns. Execute TMS protocols measuring motor cortex excitability, intracortical inhibition, and cortical silent periods. Collect CSF via lumbar puncture and plasma samples for biomarker analysis (BDNF, phospho-DARPP-32, FosB, synaptophysin levels) using ELISA and multiplex assays. Phase 3 (Months 19-24): For DBS candidates (n=20), perform intraoperative microelectrode recordings from subthalamic nucleus and globus pallidus