Alterations in functional brain connectivity following treatment for restless legs syndrome: The role of symptom improvement in restoring functional connectivity

Summary The pathophysiology of restless legs syndrome (RLS) remains incompletely understood. Although several studies have investigated the alterations of brain connectivity as one of the pathophysiological mechanisms of RLS, there are only few reports on functional connectivity changes after RLS treatment. Forty‐nine patients with newly diagnosed RLS and 50 healthy controls were prospectively enrolled. The patients underwent resting‐state functional magnetic resonance imaging (rs‐fMRI) at baseline, and 39 patients underwent follow‐up rs‐fMRI, 3 months after treatment with pramipexole or pregabalin. Patients were divided into good or poor medication response groups. Functional brain connectivity was analysed using rs‐fMRI and graph theoretical analysis. Significant differences in functional connectivity were observed between the RLS patients and healthy controls. The average path length, clustering coefficient, transitivity, and local efficiency were lower (2.02 vs. 2.30, p < 0.001; 0.45 vs. 0.56, p < 0.001; 3.08 vs. 4.21, p < 0.001; and 0.71 vs. 0.76, p < 0.001, respectively) and the global efficiency was higher (0.53 vs. 0.50, p < 0.001) in patients with RLS than in healthy controls. Differences in functional connectivity at the global level were also observed between post‐ and pre‐treatment RLS patients who showed a good medication response. Transitivity in the post‐treatment group was higher than that in the pre‐treatment group (3.22 vs. 3.04, p = 0.007). Global efficiency was positively correlated with RLS severity ( r = 0.377, p = 0.007). This study demonstrates that RLS is associated with distinct alterations in brain connectivity, which can be partially normalised following symptom management. These findings suggest that therapeutic interventions for RLS modulate brain function, emphasising the importance of symptom‐focussed treatment in managing RLS.