Objective: To evaluate the functional connectivity patterns of basal ganglia subdivisions in relation to dopamine transporter density and motor features in patients with PD at baseline and longitudinally.

Background: Resting-state functional magnetic resonance imaging (fMRI) has demonstrated that basal ganglia functional connectivity is altered in Parkinson’s disease (PD) as compared to healthy subjects. However, such functional connectivity alterations have not been related to the dopaminergic decline that occurs in PD over time.

Methods: We assessed functional connectivity of the basal ganglia subdivisions during resting-state fMRI and dopamine transporter density using 11C-PE2I PET in thirty PD patients at baseline. Of these, 15 PD patients were rescanned after 19.9±3.8 months. A seed-based approach was used to analyse resting-state fMRI data. 11C-PE2I binding potential (BPND) was calculated for each participant with the seed regions-of-interest. PD patients were assessed for disease severity (UPDRS-III) in the off-medication status at baseline and follow-up.

Results: At baseline, functional connectivity of the striatum with substantia nigra (SN) and supplementary motor area (SMA) were significantly positively correlated with striatal 11C-PE2I BPND. Over time, reduced functional connectivity of posterior putamen with SN and SMA were significantly associated with decreases in posterior putamen 11C-PE2I BPND. Furthermore, positive correlations between Δ posterior putamen functional connectivity and Δ bradykinesia-rigidity sub-scores were found in the left parahippocampal gyrus extending to midbrain including SN.

Conclusions: Our findings suggest that basal ganglia functional connectivity is related to the integrity of the dopamine system in patients with PD and the severity of motor symptoms. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool to study functional connectivity changes in PD over time and to assess the effect of therapies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-connectivity-changes-in-relation-to-dopaminergic-decline-in-parkinsons-over-time-a-resting-state-fmri-and-11c-pe2i-pet-imaging-study/