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

Abstract

Background and purposeFunctional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients.MethodsEighty‐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.ResultsPatients 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.ConclusionsNetworks 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.

Alterations of Functional Connectivity in Patients With Restless Legs Syndrome

“…The European study described above that identified changes in the salience network also used graph theory to conduct a network analysis of patients with RLS. 16 Compared with healthy controls, patients with RLS had considerably higher clustering coefficients and local efficiencies in the motor and frontal regions, and significantly lower clustering coefficients in the central sulcus, central opercular cortex, and temporal, parieto-occipital, cuneus, and occipital regions. The authors hypothesized that changes in the motor areas could be associated with the need of patients with RLS to move.…”

“…Alterations of the salience network were additionally confirmed by a recent rs-fMRI study conducted in Europe with a large sample of 82 patients with RLS and 82 healthy controls. 16 The connectivity of 12 resting-state networks, including the salience network, was investigated using the independent-component analysis method. Connectivity within the salience network and the executive and cerebellar networks was found to be significantly higher in the patients with RLS than in the healthy controls.…”

Restless Legs Syndrome: Known Knowns and Known Unknowns

“…The hypothesis that RLS may represent a network disorder, rather than a purely dopaminergic one, is also supported by recent evidence coming from functional connectivity studies. Tuovinen and coworkers reported that patients with RLS have increased connectivity within salience and executive networks and a reduced cerebello-frontal connectivity [ 47 ]. The observation that RLS is a multipathway network disorder has relevant therapeutic implications and suggests the possibility to identify new non-dopaminergic therapeutic targets.…”

Analysis of Brain Activity Changes in Patients with Parkinson’s Disease Based on Resting-State Functional Magnetic Resonance Imaging

“…The principle is mainly in the frequency range of 0.01–0.08 H, which reflects the spontaneous activity changes of neurons in the resting state; the strength of ALFF amplitude can reflect the strength of neuronal activity [ 17 ]. The local consistency analysis method is a new resting-state functional magnetic resonance data postprocessing method first proposed by Tuovinen et al [ 18 ]. Its theoretical basis is mainly that there is a high degree of voxels in the same brain area when it is activated.…”

“…The low-frequency amplitude and local consistency algorithm use different methodologies to evaluate brain function and changes in spontaneous neuronal activity from different perspectives. At present, the pathophysiological mechanism of PD patients with cognitive impairment cannot be fully clarified, and imaging diagnosis lacks objective and unified standards [ 18 ]. However, the functional abnormalities of PD associated with cognitive impairment and other brain-related diseases often occur before clinical symptoms, and the morphological changes appear.…”