Objective: To investigate the functional connectivity changes of dorsal raphe (DR) and median raphe (MR) nucleus in patients with PD from the prodromal to advanced stage, and their associations with clinical symptoms.

Background: Parkinson’s disease (PD) is characterized by serotonergic system abnormalities and brainstem serotoninergic nuclei (raphe nuclei) dysfunction.

Method: We used resting-state functional MRI to examine functional connectivity (FC) alterations of DR and MR in 36 drug-naïve (PD_denovo, average 1.41 years-duration), 50 levodopa treated early stage (PD_ED, average 1.87 years-duration), and 43 more advanced (PD_LD, average 7.28 years-duration) patients with PD, 41 idiopathic rapid eye movement sleep behavior disorder (iRBD) patients, and 46 controls. Associations between dysconnectivity and clinical features were explored using correlation analysis.

Results: Compared to controls, both DR and MR were hypo-connected with the limbic areas and occipital lobe in iRBD, and the hypo-connectivity extended to the other regions of limbic circuits, thalamus, pons, and cortical regions in PD. Compared to iRBD, DR in PD_denovo showed compensatory hyper-connectivity with the midbrain, whereas DR in PD_LD showed hypo-connectivity with the limbic circuits. Compared to PD_denovo, DR and MR in PD_LD showed hypo-connectivity with the midbrain. The disease duration and the severity of depression, olfaction, and apathy were correlated with hypo-connectivity of DR and MR with cortico-limbic circuits and cerebellum in levodopa-treated PD.

Conclusion: Our findings highlight the dysfunctions of raphe nuclei at different stages of PD and their prominent role in non-motor symptoms in levodopa-treated PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dysconnectivity-profiles-of-raphe-nuclei-in-parkinsons-disease-from-prodromal-to-advanced-stage/