Differential functional connectivity in thalamic and dopaminergic pathways in restless legs syndrome: a meta-analysis

Restless legs syndrome (RLS) is a sensorimotor disorder with alterations in somatosensory processing in association with a dysfunctional cerebral network, involving the basal ganglia, limbic network, and sensorimotor pathways. Resting state functional magnetic resonance imaging (MRI) is a powerful tool to provide in vivo insight into functional processing and as such is of special interest in RLS considering the widespread pattern of networks involved in this disorder. In this meta-analysis of resting state functional MRI studies, we analyzed the preponderance of functional connectivity changes associated with RLS and discussed possible links to sensorimotor dysfunction and somatosensory processing.

A systematic research using the online library PubMed was conducted and a total of seven studies passed the inclusion criteria of the meta-analysis. The results of these studies were merged and a statistical probability map was generated that indicated the likelihood of functional connectivity changes within the combined cohort, both for increased and decreased connectivity.

The meta-analysis demonstrated decreased functional connectivity within the dopaminergic network in participants with RLS compared with healthy controls, including the nigrostriatal, mesolimbic, and mesocortical pathways. Increased functional connectivity was observed bilaterally in the thalamus, including its ventral lateral, ventral anterior, and ventral posterior lateral nuclei, and the pulvinar.

Sensorimotor dysfunction in RLS seems to be reflected by decreased functional connectivity within the dopaminergic pathways. Network extension in the thalamus can be regarded as an adaptation to somatosensory dysfunction in RLS. This differential functional connectivity pattern extends prior findings on cerebral somatosensory processing in RLS and offers an explanation for the efficacy of dopaminergic treatment.