Objective: This study aims to explore pathways of reduced striatal dopamine synthesis in PD that may affect striato-cortical connectivity and implicate in altered glucose metabolism in the affected regions.

Background: In PD, reduced dopaminergic projections from the substantia nigra to the putamen cause disruptions in the direct basal ganglia pathway, which may affect functional connectivity (FC) to remote regions. FC between the basal ganglia and other areas is known to be severely affected in PD¹. Reduced connectivity with the putamen may have an effect on activity in affected cortical areas.

Methods: Sixty PD patients (19female, 65 ± 9.9 years old, mean H&Y stage 2.3) and 25 healthy controls (13 female, 63.5 ± 7.6 years old) were examined with three different imaging methods: F-Dopa PET, resting state (rs) fMRI and FDG PET. Patients were scanned in the OFF medication state. Analysis was performed in SPM 12. After preprocessing, F-Dopa images were first compared between groups. The peak coordinates of dopamine uptake reduction in patients were used as a seed to perform a seed-based analysis of rs-FC: spontaneous BOLD-signal fluctuations in the seed region were correlated with the signal from every other voxel in the brain. The regions where FC was reduced were then examined in FDG PET.

Results: A preliminary analysis of a representative subgroup found reduced dopamine uptake in patients in the bilateral posterior putamen, more significantly in the right hemisphere. Both regions had reduced rs-FC to the bilateral medial prefrontal cortex (mPFC) in PD patients (right: p<0.05 cluster-level FWE-corrected, left: p<0.05 uncorrected). In addition, the right putamen demonstrated reduced rs-FC to the left precuneus (p<0.05 cluster-level FWE-corrected). At the time of abstract submission, analysis was still in progress. Final results will be presented.

Conclusions: Reduced dopamine uptake in the putamen is associated with dysconnectivity between the putamen and the mPFC in PD. The more affected putamen also showed reduced FC with the precuneus. As the mPFC and precuneus are part of the default mode network (DMN), dopamine reduction in the putamen may be linked with decreased putamen-DMN rs-FC. Further analysis will focus on correlating dopamine uptake with FC.

References:

1. Tahmasian, M., L. M. Bettray, T. van Eimeren, A. Drzezga, L. Timmermann, C. R. Eickhoff, S. B. Eickhoff and C. Eggers (2015). “A systematic review on the applications of resting-state fMRI in Parkinson’s disease: Does dopamine replacement therapy play a role?” Cortex 73: 80-105.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/link-between-striatal-dopamine-uptake-and-cortical-dysconnectivity-in-parkinsons-disease/