Common and unique dysconnectivity profiles of dorsal and median raphe in Parkinson's disease

Abstract

The serotonergic (5-HT) system, which undergoes degeneration in Parkinson's disease (PD), is involved in the pathogenesis of motor and nonmotor symptoms. The dorsal raphe (DR) and median raphe (MR) nuclei are the main source of 5-HT neurons, however, brain connectivity changes in these two nuclei have not been delineated in PD. Here we used resting-state fMRI (rs-fMRI) to characterize functional connectivity profiles of DR and MR and further examine the associations between dysconnectivity of raphe nuclei and clinical phenotypes of PD. We found that DR and MR commonly hypo-connected with the sensorimotor, temporal, and occipital cortex, limbic system, left thalamus, putamen, and cerebellum in PD. DR had unique decreased connectivity with the bilateral prefrontal and cingulate cortices, while MR had lower connectivity with the pons. Moreover, reduced connectivity of DR correlated with depression, drowsiness, and anxiety, whereas dysconnectivity of MR correlated with depression, cognitive deficits, sleep disturbances, and pain. Our findings highlight the complex roles of raphe nuclei in motor and nonmotor symptoms, providing novel insights into the neurophysiological mechanisms underlying pathogenesis of PD.