Abstract
Idiopathic restless legs syndrome (RLS) is a sensorimotor disorder and is suggested to be caused by central nervous system abnormalities. Non-invasive transcutaneous spinal direct-current stimulation (tsDCS) was recently used for RLS therapy. However, the neurophysiological basis of tsDCS treatment is still unknown. In this study, we explored the neural basis of tsDCS in 15 RLS patients and 20 gender- and age-matched healthy controls using resting-state functional magnetic resonance imaging. We calculated the whole-brain voxel-wise fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and weighted degree centrality (DC) to characterize the intrinsic functional activities and the local and global functional integration. We found that tsDCS can effectively improve the sleep and RLS symptoms in RLS patients. Moreover, after tsDCS therapy, the RLS patients showed decreased fALFF in the right anterior insula/temporal pole, decreased ReHo in the supplementary motor area, increased weighted DC in the left primary visual cortex, and decreased weighted DC in the right posterior cerebellum. The changed patterns were consistent with that found between RLS patients and healthy controls. The weighted DC in the left primary visual cortex after treatment and the fALFF in the right anterior insula/temporal pole before treatment were significantly and marginally correlated with sleep and RLS symptom scores, respectively. These results revealed that tsDCS can normalize the functional patterns of RLS patients and is an effective way for RLS therapy. Our findings provide the neurophysiological basis for tsDCS treatment and may facilitate understanding the neuropathology of RLS and directing other neuromodulation treatments.
Highlights
The restless legs syndrome (RLS) is a common sensorimotor disorder, and the prevalence of the syndrome is between 3 and 9% in the general population (Phillips et al, 2000; Rothdach et al, 2000)
Paired t-tests were performed for clinical characteristics, and it was found that the RLS patients showed significantly decreased International RLS Rating Scale (IRLS-RS) (p < 10−6) and Pittsburgh Sleep Quality Index (PSQI) (p < 10−4) scores after transcutaneous spinal direct-current stimulation (tsDCS) compared with before treatment (Table 1)
We found that effective tsDCS treatment can decrease the local and global functional integration of supplementary motor area (SMA) and the cerebellum, which indicated that the functional segregation of SMA and the reduced excessive activity of the cerebellum are important for alleviating the RLS symptoms and may be the neuropathology tsDCS Modulates Functions in RLS
Summary
The restless legs syndrome (RLS) is a common sensorimotor disorder, and the prevalence of the syndrome is between 3 and 9% in the general population (Phillips et al, 2000; Rothdach et al, 2000). Dopaminergic medication is the main therapeutic approach for RLS, but given augmentation and the side effects of medication (Paulus and Trenkwalder, 2006; Earley and Silber, 2010; Allen et al, 2011; García-Borreguero and Williams, 2011), currently, non-pharmacological neuromodulation therapy has become a more and more popular approach for brain disorder treatment as it has less side effects. A recent study using the non-invasive and painless transcutaneous spinal directcurrent stimulation (tsDCS) technique demonstrated that tsDCS can reduce spinal cord excitability and can effectively alleviate the symptoms of RLS patients (Heide et al, 2014). This finding indicated that tsDCS may open a new avenue for RLS therapy. The neurophysiological basis of tsDCS therapy for RLS remains unclear
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