Alterations of Functional Connectivity in Patients With Restless Legs Syndrome

Abstract

Restless legs syndrome (RLS) is a common neurological illness marked by a strong desire to move one’s legs, usually in association with uncomfortable sensations. Recent studies have investigated brain networks and connectivity in RLS. The advent of network analysis has greatly improved our understanding of the brain and various neurological disorders. A few studies have investigated alterations in functional connectivity in patients with RLS. This article reviews functional connectivity studies of patients with RLS, which have identified significant alterations relative to healthy controls in several brain networks including thalamic, salience, default-mode, and small-world networks. In addition, network changes related to RLS treatment have been found, including to repetitive transcranial magnetic stimulation, transcutaneous spinal cord direct-current stimulation, and dopaminergic drugs. These findings suggest that the underlying pathogenesis of RLS includes alterations in the functional connectivity in the brain and that RLS is a network disorder.

Structural and functional multilayer network analysis in restless legs syndrome patients

“…These symptoms tend to worsen at night or during rest and can interfere with sleep and daily activities. Although the exact pathophysiology of RLS is unknown, it is believed to be related to altered brain connectivity, neurotransmitter dysfunction, and iron deficiency (Liu et al, 2022; Park et al, 2023; Park, Kim, Kang, et al, 2022; Park, Kim, Lee, & Cho, 2022). In addition, abnormalities in sleep plasticity and homeostasis have recently been reported to be able to contribute to sleep disorders, including RLS (Lanza et al, 2022).…”

“…In addition, abnormalities in sleep plasticity and homeostasis have recently been reported to be able to contribute to sleep disorders, including RLS (Lanza et al, 2022). Among these proposed pathophysiologies, recent research has been actively conducted on changes in brain connectivity such as those in salience, executive, and cerebellar networks in patients with restless legs syndrome (Ku et al, 2020; Park, Kim, Kang, et al, 2022; Tuovinen et al, 2021; Zhang, Zhang, et al, 2023).…”

“…Changes in the global structural connectivity in patients with RLS are identified, showing decreased segregation in the brain network compared with healthy controls (Park, Kim, Lee, & Cho, 2022). In addition, several pieces of research using the rs‐fMRI have demonstrated significant alterations of the functional connectivity in patients with RLS relative to healthy controls in several brain networks, including thalamic, salience, default‐mode, and small‐world networks (Park, Kim, Kang, et al, 2022). However, no studies have investigated the complex relationship between structural and functional connectivity using a multilayer network analysis in patients with RLS.…”