Altered Intra‐ and Inter‐Network Resting‐State Functional Connectivity is Associated with Neuropsychological Functioning and Clinical Symptoms in Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder

• Published in: Movement disorders Vol. 40; no. 4; pp. 704 - 715
• Main Authors: Roura, Ignacio, Pardo, Jèssica, Martín‐Barceló, Cristina, Oltra, Javier, Campabadal, Anna, Sala‐Llonch, Roser, Bargalló, Núria, Serradell, Mònica, Pont‐Sunyer, Claustre, Gaig, Carles, Mayà, Gerard, Montini, Angelica, Junqué, Carme, Iranzo, Alex, Segura, Bàrbara
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.04.2025; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Basal ganglia; Behavior disorders; Brain - diagnostic imaging; Brain - physiopathology; Cerebellum; Cognitive ability; Cognitive Dysfunction - physiopathology; Connectome; Eye movements; Female; Functional magnetic resonance imaging; Humans; isolated REM sleep behavior disorder; Magnetic Resonance Imaging; Male; Measuring techniques; Middle Aged; Motor task performance; Movement disorders; Nerve Net - diagnostic imaging; Nerve Net - physiopathology; Neural networks; neuroimaging; Neuropsychological Tests; Neuropsychology; prodromal alpha‐synucleinopathies; Psychology; REM sleep; REM Sleep Behavior Disorder - diagnostic imaging; REM Sleep Behavior Disorder - physiopathology; resting‐state functional connectivity; Sensorimotor system; Sleep disorders; resting‐state functional connectivity; neuropsychology; prodromal alpha‐synucleinopathies; isolated REM sleep behavior disorder; neuroimaging
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.30126

Background Isolated rapid‐eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal behaviors in REM sleep and is considered as a prodromal symptom of alpha‐synucleinopathies. Resting‐state functional magnetic resonance imaging (rsfMRI) studies have unveiled altered functional connectivity (rsFC) in patients with iRBD. However, the associations between intra‐ and inter‐network rsFC with clinical symptoms and neuropsychological functioning in iRBD remain unclear. Objective To characterize intra‐ and inter‐network rsFC in iRBD patients using a data‐driven approach and to assess its associations with clinical features and cognitive functioning. Methods Forty‐two patients with iRBD and 45 healthy controls (HC) underwent rsfMRI and comprehensive neuropsychological testing. Resting‐state networks were characterized using independent component analyses. Group differences in intra‐ and inter‐network rsFC and their associations with clinical and neuropsychological data were studied. A threshold of corrected P < 0.05 was used in all the analyses. Results iRBD patients displayed lower intra‐network rsFC within basal ganglia, visual, sensorimotor, and cerebellar networks, relative to HC. Mean rsFC strength within the basal ganglia network positively correlated with processing speed and negatively with the non‐motor symptoms in iRBD patients. Reduced inter‐network rsFC between sensorimotor and visual medial networks was observed in iRBD patients, which was associated with global cognitive status. Conclusions iRBD is characterized by both reductions in intra‐network rsFC in cortical and subcortical networks and inter‐network dysconnectivity between sensorimotor and visual networks. Abnormalities in intra‐ and inter‐network rsFC are associated with cognitive performance and non‐motor symptoms, suggesting the utility of both rsFC measures as imaging markers in prodromal alpha‐synucleinopathies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.