Objective: This study aims to assess how serotonergic pathological derangement may produce alterations in Parkinson’s disease (PD) functional connectivity, by means of a multimodal neuroimaging approach.

Background: PD is characterized by progressive loss of dopaminergic and serotonergic terminals in cortical and subcortical regions. The contribution of serotonergic terminals loss to brain functional connectivity remains unclear.

Method: We identified the hub regions with reduced serotonergic terminals by using the principal component analysis (PCA)-based scaled sub-profile model to [11C]DASB distribution volume ratio images. We generated the serotonergic connectivity network including the serotonergic pathological hubs identified with [11C]DASB PCA into the resting state functional magnetic resonance (rs-fMRI) connectivity analysis, also exploring graph theory measures. We aimed to investigate in a multimodal fashion the alterations in serotonergic connectivity network in idiopathic PD patients compared to healthy controls.

Results: Raphe nuclei, midbrain, thalamus, pons, medulla, basal ganglia, insula, amygdala, hippocampus, cerebellum, frontal, occipital and temporal cortices were identified as pathological hubs showing loss of [11C]DASB binding in PD patients. As emerged from both connectivity and graph theory analyses, the serotonergic network presented a prevalent local connectivity dysfunction. PD patients showed reduced local connectivity in thalamus, putamen and occipital cortex (FDR-correction p<0.05). Accordingly, these regions showed significant reductions of clustering coefficient, local efficiency and degree, measures indicating local connectivity dysfunction for graph theory.

Conclusion: This study provides evidence of altered serotonergic network connectivity in idiopathic PD, which is characterized by local alterations in hallmark regions for PD pathology. This multi-modal molecular and functional connectivity approach was critical for understanding the effect of PD pathology on brain connectomics. Future studies are needed to explore if long-distance changes will affect serotonergic network in more advanced PD stages, and to explore the association between serotonergic network connectivity alterations and PD non-motor symptoms. This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evidence-of-altered-serotonergic-network-in-parkinsons-disease-by-using-a-multi-modal-mri-and-pet-imaging-approach/