Objective: Using resting-state functional MRI, we investigated intrinsic brain networks connectivity at baseline in a cohort of drug-naïve Parkinson’s disease (PD) patients which successively developed treatment-related motor complications (PD-Fluct) over a 4-years follow-up period compared with patients who did not (PD-no-Fluct).

Background: Dopamine replacement therapy (DRT) is the most effective treatment for patients with PD. However, chronic DRT may be complicated by the evolution of motor complications, (i.e. motor response fluctuations and levodopa-induced dyskinesias) which develop progressively over the disease course. Risk factors include long treatment duration, high initial dose of levodopa, young age at onset, female sex, but yet these factors alone cannot predict whether an individual patient will develop such treatment-related complications over time.

Method: Baseline 3Tesla MRI images of 88 drug-naïve PD patients and 20 healthy controls (HC) were analyzed. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major motor and extra-motor resting state networks. Additionally, a region-of-interest analysis was performed within the basal ganglia. Sex and age were run as covariates. After the baseline assessments, all patients started DRT and were followed for an observation period lasting a maximum of 4 years. Multivariate regression analyses were used to investigate baseline predictors of motor complications development.

Results: At baseline, an increased connectivity within the default-mode and the frontoparietal networks as well as within the basal ganglia were detected in PD-Fluct patients compared with PD-no-Fluct. Interestingly, no differences were shown between PD-Fluct patients at baseline and HC within the basal ganglia. Functional connectivity changes at the disease onset showed to be an independent predictor of motor complications at 4-year follow-up.

Conclusion: Our findings demonstrated that specific functional connectivity changes may characterize drug-naïve PD patients more prone to develop treatment-related complications while under DRT. We hypothesize that these findings may reflect the presence of early differences within the dopaminergic pathways and might predict development of motor complications over time.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/intrinsic-brain-functional-connectivity-predicts-treatment-related-motor-complications-in-drug-naive-parkinsons-disease-patients/