Altered Functional Connectivity Between Insula and Precuneus in Isolated REM Sleep Behavior Disorder

Functional connectivity between the insula and precuneus may be linked to cognitive function in patients with isolated REM sleep behavior disorder.

Connectivity between the insula and precuneus may be associated with cognitive function among patients with isolated rapid eye movement sleep behavior disorder (iRBD), according to the results of a cross-sectional study published in Sleep Medicine.

Study researchers recruited patients (n=50) diagnosed by video-polysomnography with iRBD at Seoul National University Hospital Sleep Clinic and healthy controls (n=20) for this study. They assessed participants by multivariate pattern analysis on the basis of structural magnetic resonance imaging (MRI) and resting-state functional MRI scans.

Patients with iRBD and those in the control group had a mean age of 66.5 (standard deviation [SD], ±6.9) and 68.1 (SD, ±3.4) years, respectively, and 58.0% and 55.0% were men, respectively. Patients had been diagnosed with iRBD an average of 7.1 (SD, ±4.6) years previously, and compared with controls had higher Rapid Eye Movement Sleep Behavior Disorder Questionnaire scores (P <.001), Geriatric Depression Scale scores (GDS; P =.001), Scales for Outcomes in Parkinson Disease-Automatic questionnaire scores (P =.001), and spent fewer years in education (P =.047).

The multivariate pattern analysis found 1 significant cluster located in the left posterior insular cortex and 2 located in the precuneus.

Patients with iRBD exhibited a positive correlation between the functional connectivity of the insular-precuneus cluster 1 and Montreal Cognitive Assessment (MoCA) scores (r, 0.317; P =.025). MoCA scores trended toward a positive correlation with functional connectivity of the precuneus cluster 2 (r, 0.271; P =.057).

GDS and MoCA scores were negatively correlated (r, -0.294; P =.038). After adjusting for GDS, MoCA scores correlated with the functional connectivity in both clusters in the precuneus (cluster 1: adjusted r, 0.337; P =.018; cluster 2: adjusted r, 0.371; P =.009).

Delayed recall was correlated with functional connectivity of cluster 2 in the left posterior insula (r, 0.282; P =.047) and was more strongly correlated after correcting for GDS (adjusted r, 0.333; P =.019).

This study was limited by its small sample size and the cross-sectional design, which did not allow for causative relationships to be assessed.

Study researchers concluded that their findings emphasized “the insula as an important neural correlate associated with iRBD… [Functional connectivity] changes may be a biomarker of incipient cognitive decline, and larger longitudinal studies will be necessary to confirm the causal relationship between FC changes and cognitive impairment in iRBD.”


Byun J-I, Cha KS, Kim M, et al. Altered insular functional connectivity in isolated REM sleep behavior disorder: a data-driven functional MRI study. Sleep Med. 2021;79:88-93. doi:10.1016/j.sleep.2020.12.038