“…Beyond these considerations, additional factors such as disease heterogeneity, disease stages, or even age-related effects could further contribute the differences observed across studies. In this context, it is not surprising to see that the significant differences observed between RLS patients and healthy controls for R 2 * (caudate) and QSM (putamen and red nucleus) do not align and may reflect secondary factors unrelated to iron such as a differential involvement of aging-related process, e.g., changes in myelin content ( Möller et al, 2019 , Hametner et al, 2018 , Treit et al, 2021 ). This hypothesis is in line with recent evidence of morphological alterations and atrophy within regions of the basal ganglia and the limbic system in RLS ( Mogavero et al, 2021 ), supporting the concept of RLS as a complex network disorder, with the thalamus representing a crucial node within different networks, including the sensorimotor and limbic pathways.…”