Altered insular functional connectivity in isolated REM sleep behavior disorder: a data-driven functional MRI study

Objective: Functional connectivity (FC) changes can occur prior to structural changes. This study aimed to evaluate data-driven whole-brain FC associated with isolated rapid eye movement sleep behavior disorder (iRBD) using multivariate pattern analysis (MVPA). Methods: This was a cross-sectional study of 50 polysomnography-confirmed iRBD patients and 20 age- and sex-matched controls. We used MVPA implemented in the connectome-MVPA CONN toolbox to identify data-driven seed regions for post hoc seed-to-voxel connectivity analysis. The association between FC changes and clinical characteristics, including cognition, depression, autonomic function, and daytime sleepiness, was evaluated. Results: MVPA revealed one significant cluster located in the left posterior insular cortex. Seed-to-voxel FC analysis using the cluster as a seed showed significantly reduced FC with two clusters located in the precuneus in iRBD patients compared to the controls. The degree of FC was associated with the Montreal Cognitive Assessment-Korean version scores (r = 0.317, p = 0.025). Conclusion: This study emphasizes the insula as an important neural correlate associated with iRBD that was associated with cognitive function.