LAUSR

Functional brain connectivity studies revealed alterations within thalamic, salience, and default mode networks in patients with restless legs syndrome. The objective of this study was to characterize functional connectivity and network topology in a large cohort of patients with restless legs syndrome compared to healthy controls, and to investigate the modulatory effect of dopaminergic treatment upon connectivity. 82 patients with restless legs syndrome (untreated, n=30; on dopaminergic medication, n=42; on alpha-2-delta ligands as mono- or polytherapy combined with dopaminergic medication, n=10) and 82 individually age and gender matched healthy controls were studied with resting state functional MRI. Connectivity of twelve resting-state networks was compared with independent component analysis, and among 410 brain regions with graph theoretical modeling. Patients with restless legs syndrome showed significantly higher connectivity within salience (P=0.029), executive (P=0.001), somatomotor (P=0.050), and cerebellar (P=0.041) networks, as well as significantly (P<0.05) lower cerebello-frontal communication compared to healthy controls. Untreated patients had significantly (P<0.05) lower cerebello-parietal communication compared to healthy controls and connectivity between the thalamus and frontal regions were significantly increased in patients on dopaminergic medication compared to untreated patients and healthy controls (P<0.05). Networks with higher intra-network connectivity (i.e. salience, executive, somatomotor, cerebellar) and lower between regions connectivity (i.e. cerebello-frontal, cerebello-parietal) in restless legs syndrome correspond to regions associated with attention, response inhibitory control, and processing of sensory information. Dopaminergic medication normalizes the altered cerebello-parietal communication and increases thalamic connectivity to the prefrontal cortex suggesting that these regions are associated with the emergence of symptoms in restless legs syndrome. The study was funded by a Grant from Translational Research Fund of the government of Tyrol, Austria, and in-kind resources of the Medical University of Innsbruck.