Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study

N Tuovinen; A Stefani; T Mitterling; A Heidbreder; B Frauscher; E R Gizewski; W Poewe; B Högl; C Scherfler

doi:10.1111/ene.14577

Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study

Eur J Neurol. 2021 Feb;28(2):448-458. doi: 10.1111/ene.14577. Epub 2020 Nov 5.

Authors

N Tuovinen^{1

2}, A Stefani², T Mitterling^{2

3

4}, A Heidbreder^{2

5}, B Frauscher^{2

6}, E R Gizewski^{7

8}, W Poewe², B Högl², C Scherfler^{2

7}

Affiliations

¹ Department of Psychiatry, Psychotherapy and Psychosomatics, Division of Psychiatry I, Medical University of Innsbruck, Innsbruck, Austria.
² Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
³ Neurologie 1, Kepler Universitätsklinikum GmbH, Neuromed Campus, Linz, Austria.
⁴ Johannes Kepler University, Linz, Austria.
⁵ Department of Neurology, University Hospital Münster, Münster, Germany.
⁶ Analytical Neurophysiology Lab, Montreal Neurological Institute & Hospital, McGill University, Montreal, Quebec, Canada.
⁷ Neuroimaging Research Core Facility, Medical University of Innsbruck, Innsbruck, Austria.
⁸ Department of Neuroradiology, Medical University of Innsbruck, Innsbruck, Austria.

Abstract

Background and purpose: Functional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients.

Methods: Eighty-two 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 magnetic resonance imaging. Connectivity of 12 resting-state networks was investigated with independent component analysis, and network topology was studied with graph methods among 410 brain regions.

Results: Patients with restless legs syndrome showed significantly higher connectivity within salience (p = 0.029), executive (p = 0.001), and cerebellar (p = 0.041) networks, as well as significantly lower (p < 0.05) cerebello-frontal communication compared to controls. In addition, they had a significantly higher (p < 0.05) clustering coefficient and local efficiency in motor and frontal regions; lower clustering coefficient in the central sulcus; and lower local efficiency in the central opercular cortex, temporal, parieto-occipital, cuneus, and occipital regions compared to controls. Untreated patients had significantly lower (p < 0.05) cerebello-parietal communication compared to healthy controls. Connectivity between the thalamus and frontal regions was significantly increased (p < 0.05) in patients on dopaminergic medication compared to untreated patients and controls.

Conclusions: Networks with higher intranetwork connectivity (i.e., salience, executive, cerebellar) and lower cerebello-frontal connectivity in the restless legs syndrome patients, as well as lower cerebello-parietal connectivity in untreated patients, correspond to regions associated with attention, response inhibitory control, and processing of sensory information. Intact cerebello-parietal communication and increased thalamic connectivity to the prefrontal regions in patients on dopaminergic medication suggests a treatment effect on thalamus.

Keywords: brain connectivity; functional magnetic resonance imaging; restless legs syndrome; sleep wake disorders.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Brain Mapping
Case-Control Studies
Cerebral Cortex
Humans
Magnetic Resonance Imaging
Restless Legs Syndrome* / diagnostic imaging
Restless Legs Syndrome* / drug therapy
Thalamus / diagnostic imaging