Effects of levodopa on the motor reserve network change with progression of Parkinson's disease

Recent studies have highlighted the role of the motor reserve network (MRN) in early-stage Parkinson's disease (PD). However, the impact of acute levodopa administration on functional organization of the MRN particularly across different stages of PD remains unclear.

Thirty-three PD patients underwent an acute levodopa challenge with functional MRI scanning in "off," "on," and intermediate states. Additionally, 37 healthy controls (HCs) were scanned once. Graph theory was used to assess the global and regional topological characteristics of the MRN in PD patients (off and on states) and HCs. The correlation between MRN topology changes and motor symptom improvement was examined. A further analysis classified PD patients into mild (PD-mild) and moderately advanced (PD-moderate) stages to investigate drug time effects and disease severity interactions in the MRN.

Compared with HCs, lower nodal efficiency was shown in the left inferior frontal gyrus in the MRN in PD off state. Compared with PD off state, decreased global efficiency of the MRN and betweenness centrality (BC) in the right superior occipital cortex (SOC) were shown in PD on state. Decreased BC in the right SOC was significantly correlated with improvement of clinical symptoms, especially tremor subscale. Surprisingly, the pattern of regional topological properties in the MRN was reversed across PD-mild and PD-moderate in the right olfactory cortex and left putamen.

This study reveals levodopa-induced alterations in MRN topological attributes in PD, with stage-specific differences. These findings deepen our understanding of MRN functional reorganization and its clinical relevance in PD.