Abstract
The effects of dopaminergic therapy for Parkinson’s disease (PD) on the brain functional architecture are still unclear. We investigated this topic in 31 PD patients (disease duration: 11.2 ± (SD) 3.6 years) who underwent clinical and MRI assessments under chronic dopaminergic treatment (duration: 8.3 ± (SD) 4.4 years) and after its withdrawal. Thirty healthy controls were also included. Functional and morphological changes were studied, respectively, with eigenvector centrality mapping and seed-based connectivity, and voxel-based morphometry. Patients off medication, compared to controls, showed increased connectivity in cortical sensorimotor areas extending to the cerebello-thalamo-cortical pathway and parietal and frontal brain structures. Dopaminergic therapy normalized this increased connectivity. Notably, patients showed decreased interconnectedness in the medicated compared to the unmedicated condition, encompassing putamen, precuneus, supplementary motor and sensorimotor areas bilaterally. Similarly, lower connectivity was found comparing medicated patients to controls, overlapping with the within-group comparison in the putamen. Seed-based analyses revealed that dopaminergic therapy reduced connectivity in motor and default mode networks. Lower connectivity in the putamen correlated with longer disease duration, medication dose, and motor symptom improvement. Notably, atrophy and connectivity changes were topographically dissociated. After chronic treatment, dopaminergic therapy decreases connectivity of key motor and default mode network structures that are abnormally elevated in PD off condition.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder[1], but its definite cure still represents an unmet need[2]
Comparing PD-OFF and controls, we found a significant increase in eigenvector centrality (EC) in the patients in the bilateral pre- and post-central gyri and in the precuneus (Table S3)
This study investigated the Dopaminergic therapy (DT) effect on brain connectivity in advanced PD after several years of pharmacological treatment
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder[1], but its definite cure still represents an unmet need[2]. “molecular nexopathy”)[4,5], provides a novel framework for the study of treatment-induced brain changes In this view, brain functional connectivity assessed with magnetic resonance imaging (MRI) is a candidate biomarker to investigate both brain changes related to the PD itself and their modulation by means of different therapies. The effect of DT after several years of chronic pharmacological treatment in PD has not been investigated yet with brain rs-fMRI To address this issue, we selected a patient cohort with longer disease duration and under chronic DT. Given the exploratory nature of our research question, we preferred a conservative approach to whole-brain analysis, without constraints from a priori assumptions To fulfill this aim we opted for eigenvector centrality (EC) mapping[21], a common graph-based method for network analysis implemented by the Google PageRank algorithm[22]. We investigated the clinico-functional correlations between centrality measures and clinical variables, such as overall motor impairment, as assessed with the Unified Parkinson’s Disease Rating Scale-III (UPDRS-III), disease duration, as well as treatment dose and duration
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