Abnormality of insular functional connectivity in uremic restless legs: A resting state functional magnetic resonance study

Dun DING

ABSTRACT

Objective:

To investigate the changes of insular functional connectivity in patients with uremic restless legs syndrome (uRLS) using seed-based resting-state functional connectivity analysis so as to explore the related risk factors for RLS.

Methods:

3D high-resolution structural imaging was applied in 29 patients with uremic restless legs (uRLS group) and 29 healthy volunteers (control group) with maintenance hemodialysis. The greymatter volume of the insular cortex was assessed using a voxel-based morphometry (VBM) analysis and functional connectivity of insular variation was evaluated by a seed-based correlation analysis, while the seed was chosen as the significant difference of grey matter volume. Pearson correlation analysis was used to explore the significant correlation between functional connectivity and RLS score. The relationship between brain alterations and clinical variables were investigated with Logistic stepwise multiple regression analysis.

Results:

Compared with that in the control group, the area with reduced gray matter volume in the uRLS group was located on the left posterior insula (P<0.05, FWE correction). Taking the left post insular as a seed region, we further found reduced functional connectivity in patients mainly between the insular and primary sensorimotor cortex (S1), supplementary motor areas (SMA), and posterior mid-cingulate gyrus (P<0.05, FDR corrected). In uRLS group, the severity score of RLS was negatively correlated with insular-S1 functional connectivity (P<0.05, FDR corrected), while the hemoglobin level was negetively correlated with functional connectivity degree of insular-S1 (r=-0.449, P=0.015, FDR corrected).

Conclusion:

The altered morphology of the post insular cortex was revealed in uRLS patients. Abnormal sensorimotor activities in patients with RLS were closely associated with reduced functional connectivity of insular-S1. Low hemoglobin level was the most important risk factor for the abnormal functional connectivity of the brain.