Normalization effect of dopamine replacement therapy on brain functional connectome in Parkinson's disease

Abstract

AbstractDopamine replacement therapy (DRT) represents the standard treatment for Parkinson's disease (PD), however, instant and long‐term medication influence on patients' brain function have not been delineated. Here, a total of 97 drug‐naïve patients, 43 patients under long‐term DRT, and 94 normal control (NC) were, retrospectively, enrolled. Resting‐state functional magnetic resonance imaging data and motor symptom assessments were conducted before and after levodopa challenge test. Whole‐brain functional connectivity (FC) matrices were constructed. Network‐based statistics were performed to assess FC difference between drug‐naïve patients and NC, and these significant FCs were defined as disease‐related connectomes, which were used for further statistical analyses. Patients showed better motor performances after both long‐term DRT and levodopa challenge test. Two disease‐related connectomes were observed with distinct patterns. The FC of the increased connectome, which mainly consisted of the motor, visual, subcortical, and cerebellum networks, was higher in drug‐naïve patients than that in NC and was normalized after long‐term DRT (p‐value <.050). The decreased connectome was mainly composed of the motor, medial frontal, and salience networks and showed significantly lower FC in all patients than NC (p‐value <.050). The global FC of both increased and decreased connectome was significantly enhanced after levodopa challenge test (q‐value <0.050, false discovery rate‐corrected). The global FC of increased connectome in ON‐state was negatively associated with levodopa equivalency dose (r = −.496, q‐value = 0.007). Higher global FC of the decreased connectome was related to better motor performances (r = −.310, q‐value = 0.022). Our findings provided insights into brain functional alterations under dopaminergic medication and its benefit on motor symptoms.