Objective: This study aimed to investigate the neural mechanisms of motor alterations in idiopathic REM sleep behavior disorder (iRBD) and to determine whether abnormalities in motor-related brain networks and brain-behavior coupling are associated with impaired fine motor performance.

Background: Growing evidence suggests that subtle motor abnormalities may emerge in iRBD before the clinical diagnosis of PD. Neuroimaging studies have reported altered motor-related brain networks and abnormal functional connectivity (FC) across sensorimotor, visual, and cerebellar networks. However, the relationship between brain connectivity alterations and motor performance remains unclear.

Method: A total of 48 patients with iRBD and 27 HCs underwent clinical assessment and resting-state fMRI. Seed-based whole-brain functional connectivity analysis focused on motor-related networks. Multivariable linear regression examined associations between altered connectivity and Purdue Pegboard Test (PPT) performance, and interaction analyses assessed group differences in brain-behavior relationships.

Results: Compared with healthy controls, patients with iRBD showed widespread alterations in resting-state FC across motor-related networks, predominantly decreased connectivity between sensorimotor regions and occipital areas (e.g., lingual gyrus, calcarine cortex, and cuneus), as well as reduced connectivity between the right putamen and right middle temporal gyrus. Abnormal connectivity was also observed in cerebellar regions, including right Crus I, left lobule VI, and right lobule IX. Within the iRBD group, several altered connections were significantly associated with Purdue Pegboard Test performance, such as the negative correlation between dominant-hand dual-task cost and connectivity of right Crus I-lobule IX (β = −55.74, p = 0.034). Interaction analyses further revealed altered brain-behavior coupling in iRBD.

Conclusion: Patients with iRBD exhibit widespread alterations in resting-state FC within motor-related networks. Several cerebellar connections were associated with fine motor and dual-task performance on the PPT, suggesting a role of cerebellar-motor pathways in early motor and cognitive-motor integration impairments. Altered brain-behavior coupling further indicates network reorganization in prodromal synucleinopathies and highlights potential neuroimaging biomarkers of disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neural-mechanisms-of-motor-dysfunction-in-idiopathic-rem-sleep-behavior-disorder-an-rs-fmri-study-based-on-the-purdue-pegboard-test/