Little Change in Functional Brain Networks Following Acute Levodopa in Drug-Naïve Parkinson's Disease

Abstract

Objective: The objective of this study was to investigate the effects of levodopa on functional brain networks in Parkinson's disease.

Methods: We acquired resting state functional magnetic resonance imaging in 30 drug-naïve participants with Parkinson's disease and 20 age-matched healthy controls. Each participant was studied following administration of a single oral dose of either levodopa or placebo in a randomized, double-blind, crossover design.

Results: The greatest observed differences in functional connectivity were between Parkinson's disease versus control participants, independent of pharmacologic intervention. By contrast, the effects of levodopa were much smaller and detectable only in the Parkinson's disease group. Moreover, although levodopa administration in the Parkinson's disease group measurably improved motor performance, it did not increase the similarity of functional connectivity in Parkinson's disease to the control group.

Conclusions: We found that a single, small dose of levodopa did not normalize functional connectivity in drug-naïve Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; drug naive; fMRI; levodopa; resting-state functional connectivity.

Figure 1.

Large-scale networks in Parkinson disease and controls after L-DOPA or placebo. Mean correlation matrices in (A) PD placebo, (B) HC placebo, (C) PD L-DOPA and (D) HC L-DOPA conditions. All conditions showed strong network organization with well-defined block structure. Note generally strong positive correlations within each network (diagonal) and mixture of weaker positive and negative correlations between networks (off-diagonals). Direct comparison between groups (PD – HC) for the (E) L-DOPA and (F) placebo conditions, and between drug conditions (L-DOPA – placebo) for the (G) PD and (H) HC groups. There was a mixture of positive and negative differences. Note much larger differences between groups than between drug conditions. Color scales indicates magnitude of Z-transformed Pearson’s correlations (note different color scales for mean and difference matrices). (I) Each plot shows the relative positions of individual participants FC matrices in the first 3 dimensions from multi-dimensional scaling. Conditions are indicated by color: PD L-DOPA (blue), PD placebo (green), HC L-DOPA (red), and HC placebo (orange). Large squares represent the central tendency of each group. Note separation between PD and HC conditions, as well as lack of centroid shift with L-DOPA treatment.