Dopaminergic modulation of resting-state functional connectivity in de novo patients with Parkinson's disease

Abstract

Parkinson's disease (PD) is characterized by degenerative changes of nigral dopamine neurons, resulting in the dopaminergic denervation of the striatum. Resting state networks studies have demonstrated that dopamine modulates distinct network connectivity patterns in both a linear and a nonlinear fashion, but quantitative analyses of dopamine-dependent functional connectivity secondary to PD pathology were less informative. In the present study, we performed a correlation analysis between striatal dopamine levels assessed quantitatively by FP-CIT positron emission tomography imaging and resting-state functional connectivity in 23 drug naïve de novo patients with PD to elucidate dopamine-dependent functional networks. The major finding is that the patterns of dopamine-dependent positive functional connectivity varied depending on the location of striatal seeds. Dopamine-dependent functional connectivity with the caudate predominantly overlay pericentral cortical areas, whereas dopamine-dependent structures functionally connected with the posterior putamen predominantly involved cerebellar areas. The dorsolateral frontal area overlapped as a dopamine-dependent cortical region that was positively connected with the anterior and posterior putamen. On the other hand, cortical areas where functional connectivity from the posterior cingulate was negatively correlated with dopaminergic status in the posterior putamen were localized in the left anterior prefrontal area and the parietal area. Additionally, functional connectivity between the anterior putamen and mesiofrontal areas was negatively coupled with striatal dopamine levels. The present study demonstrated that dopamine-dependent functional network connectivity secondary to PD pathology mainly exhibits a consistent pattern, albeit with some variation. These patterns may reflect the diverse effects of dopaminergic medication on parkinsonian-related motor and cognitive performance.

Keywords: de novo Parkinson's disease; dopamine; resting-state functional connectivity.

Figure 1

Dopamine‐dependent functional connectivity between the cortex and seed region of interest in the caudate. The pericentral cortical areas exhibited significant functional connectivity with the caudate that was positively coupled with dopamine levels in the posterior putamen. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Dopamine‐dependent functional connectivity between the cortex and seed region of interest in the anterior putamen. Dopamine‐dependent positive functional connectivity was localized in the right dorsolateral frontal area (orange color), whereas in the mesiofrontal areas, functional connectivity between the cortex and the anterior putamen was negatively correlated with dopaminergic status in the posterior putamen (blue color). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Dopamine‐dependent functional connectivity from the seed region of interest in the posterior putamen. Dopamine‐dependent positive functional connectivity was localized in the right dorsolateral frontal area. Additionally, functional connectivity between the cerebellar areas and the posterior putamen was positively correlated with dopaminergic status in the posterior putamen. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Dopamine‐dependent functional connectivity between the cortex and seed region of interest in the posterior cingulate cortex. Functional connectivity from the posterior cingulate that was negatively associated with striatal dopaminergic status was involved in the left anterior prefrontal area and the parietal area (blue color). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]