Background The alteration of substantia nigra (SN) degeneration in populations at risk of Parkinson's disease (PD) is unclear. Objective We investigated free water (FW) values in the posterior SN (pSN) in asymptomatic LRRK2 G2019S mutation carriers. Methods We analyzed diffusion imaging data from 28 asymptomatic LRRK2 G2019S mutation carriers and 30 healthy controls (HCs), whereas 11 asymptomatic LRRK2 G2019S carriers and 11 HCs were followed up. FW values in the pSN were measured and compared between the groups. The relationship between longitudinal changes in FW in the pSN and dopamine transporter striatal binding ratio (SBR) was analyzed. Results FW values in the pSN were significantly elevated and kept increasing during follow‐up in asymptomatic LRRK2 G2019S carriers. There was a negative correlation between FW changes in the left pSN and SBR changes in the left putamen. Conclusion FW in the pSN has the potential to be a progression imaging marker of early dopaminergic degeneration in the population at risk of PD. © 2022 International Parkinson and Movement Disorder Society.
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.
Aims This study aimed to identify the functional connectivity (FC) changes of nucleus accumbens (NAc) subregions and characterize the association of network changes and non‐motor symptoms (NMS) in Parkinson's disease (PD). Methods We enrolled 129 PD patients and 106 healthy controls from our center and the PPMI (Parkinson's Progression Markers Initiative) database. The FC of the bilateral core and shell of the NAc were measured and compared between the two groups. We further used partial least squares correlation to reveal the relationships between altered FC of NAc subregions and manifestations of NMS of PD. Results The subregions of left core, left shell, and right core had reduced FC with extensive brain regions in PD patients compared with healthy controls. These three subregions were commonly associated with depression, anxiety, apathy, and cognitive impairment. Moreover, the left core and left shell were associated with excessive daytime sleepiness, whereas the right core was associated with olfactory impairment and rapid eye movement sleep behavior disorder. Conclusion This study for the first time identified the neural network changes of NAc subregions in PD and the associations between network changes and phenotypes of NMS. Our findings provide new insights into the pathogenesis of NMS in PD.
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