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Lookup NU author(s): Dr Jacopo Pasquini, Dr Michael FirbankORCiD, Victoria Foster, Charlotte StewartORCiD, Dr Gemma Roberts, Dr George Petrides, Emeritus Professor David Brooks, Dr Kirstie Anderson, Professor Nicola PaveseORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.Substantia nigra (SN) and locus coeruleus (LC) are two catecholaminergic, neuromelanin-rich nuclei that are affected in Parkinson’s disease (PD) and may show neuroimaging abnormalities before the onset of motor manifestations. The simultaneous, multimodal investigation of their microstructural abnormalities may provide useful insights on the spatial diffusion and tissue characteristics of neurodegeneration, and this may in turn help develop markers for disease-modifying clinical trials. Therefore, through neuromelanin-sensitive and diffusion MRI, we aimed to investigate microstructural abnormalities in those nuclei in isolated REM sleep behaviour disorder (iRBD) and PD. Fourteen participants with polysomnography-confirmed iRBD, 18 with PD and 18 healthy controls were scanned with structural, neuromelanin-sensitive and neurite orientation dispersion and density imaging (NODDI) MRI. iRBD participants also underwent dopamine transporter imaging. SN neuromelanin and NODDI diffusion parameters and LC neuromelanin signals were extracted. Motor and global cognitive assessments were also collected. iRBD and PD participants showed significantly reduced neuromelanin contrast in the LC middle section compared with healthy controls. PD also showed significantly reduced caudal LC and posterior SN neuromelanin signal. No differences in SN NODDI parameters were detected between iRBD and healthy controls. Five iRBD participants showed reduced striatal dopamine transporter. In the combined disease groups (iRBD and PD), significant associations were shown between SN neuromelanin signal and neurite density index (r = −0.610, corr-p = 0.001) and between SN neurite density index and free water fraction (r = 0.417, corr-p = 0.042). In the same group, motor scores were negatively associated with nigral neuromelanin signal (r = −0.404, corr-p = 0.044) and free water fraction (r = 0.486, corr-p = 0.018). In conclusion, iRBD participants showed significant neuromelanin loss in the LC, with a minority showing initial nigrostriatal dopaminergic abnormalities. Across the entire iRBD–PD spectrum, the association between SN neuromelanin signal loss, diffusion parameters and motor scores has the potential to capture different yet related aspects of SN degeneration.
Author(s): Pasquini J, Firbank MJ, Best L, Foster V, Stewart C, Silani V, Durcan R, Roberts G, Petrides G, Ceravolo R, Brooks DJ, Anderson KN, Pavese N
Publication type: Article
Publication status: Published
Journal: Brain Communications
Year: 2025
Volume: 7
Issue: 1
Online publication date: 21/01/2025
Acceptance date: 21/01/2025
Date deposited: 03/03/2025
ISSN (electronic): 2632-1297
Publisher: Oxford University Press
URL: https://doi.org/10.1093/braincomms/fcaf023
DOI: 10.1093/braincomms/fcaf023
Data Access Statement: Data used in the preparation of this manuscript are available upon request. The code generated in the analysis is available in the Supplementary material
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