{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:41:41Z","timestamp":1789962101873,"version":"4.0.1"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["SMA-17C-11"],"award-info":[{"award-number":["SMA-17C-11"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["K-1703"],"award-info":[{"award-number":["K-1703"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013128","name":"Multiple System Atrophy Trust","doi-asserted-by":"publisher","award":["NP61010\/18"],"award-info":[{"award-number":["NP61010\/18"]}],"id":[{"id":"10.13039\/100013128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Substantia nigra (SN) and locus coeruleus (LC) are two catecholaminergic, neuromelanin-rich nuclei that are affected in Parkinson\u2019s 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 = \u22120.610, 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 = \u22120.404, 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\u2013PD 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf023","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T18:17:39Z","timestamp":1737483459000},"source":"Crossref","is-referenced-by-count":8,"title":["Substantia nigra and locus coeruleus microstructural abnormalities in isolated rapid eye movement sleep behaviour disorder and Parkinson\u2019s disease"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-2995","authenticated-orcid":false,"given":"Jacopo","family":"Pasquini","sequence":"first","affiliation":[{"name":"Clinical Ageing Research Unit, Newcastle University , Newcastle upon Tyne NE4 5PL ,","place":["UK"]},{"name":"Department of Clinical and Experimental Medicine, University of Pisa , Pisa 56126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9536-0185","authenticated-orcid":false,"given":"Michael J","family":"Firbank","sequence":"additional","affiliation":[{"name":"Institute of Translational and Clinical Research, Newcastle University , Newcastle upon Tyne NE4 5PL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Best","sequence":"additional","affiliation":[{"name":"Regional Neurosciences Centre, Royal Victoria Hospital , Belfast BT12 6PA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Foster","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit, Newcastle University , Newcastle upon Tyne NE4 5PL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Stewart","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit, Newcastle University , Newcastle upon Tyne NE4 5PL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-3854","authenticated-orcid":false,"given":"Vincenzo","family":"Silani","sequence":"additional","affiliation":[{"name":"Department of Neurology and Laboratory of Neuroscience, Istituto Auxologico Italiano IRCCS , Milan 20149 ,","place":["Italy"]},{"name":"Department of Pathophysiology and Transplantation, Dino Ferrari Center, Universit\u00e0 degli Studi di Milano , Milan 20122 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8897-8737","authenticated-orcid":false,"given":"Rory","family":"Durcan","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Beaumont Hospital , Dublin D09 V2N0 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Roberts","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Newcastle Upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne NE1 4LP ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Petrides","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Department, Newcastle Upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne NE1 4LP ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-9406","authenticated-orcid":false,"given":"Roberto","family":"Ceravolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa , Pisa 56126 ,","place":["Italy"]},{"name":"Neurodegenerative Diseases Center, Azienda Ospedaliero Universitaria Pisana , Pisa 56126 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-2518","authenticated-orcid":false,"given":"David J","family":"Brooks","sequence":"additional","affiliation":[{"name":"Institute of Translational and Clinical Research, Newcastle University , Newcastle upon Tyne NE4 5PL ,","place":["UK"]},{"name":"Department of Nuclear Medicine and PET Centre, Institute of Clinical Medicine Aarhus University , Aarhus 8200 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstie N","family":"Anderson","sequence":"additional","affiliation":[{"name":"Regional Sleep Service, Newcastle upon Tyne NHS Hospitals NHS Foundation Trust , Newcastle upon Tyne NE1 4PL ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-6194","authenticated-orcid":false,"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[{"name":"Clinical 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