Jeonghun Ku1, Yeong Seon Lee2, Hyuk Won Chang3, Christopher J Earley4, Richard P Allen4, Yong Won Cho5. 1. Department of Biomedical Engineering, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea. 2. Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea. 3. Department of Radiology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea. 4. Department of Neurology, Johns Hopkins University, Hopkins Bayview Medical Center, Baltimore, MD, USA. 5. Department of Neurology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, South Korea. Electronic address: neurocho@gmail.com.
Abstract
OBJECTIVE: Restless legs syndrome (RLS) patients compared to controls have been found to have abnormal patterns in the default mode network (DMN) in the morning when symptom threshold is the highest and symptoms are least likely to occur. If these morning abnormalities in DMN are pertinent to disease expression, then similar or further detectable differences may be expected on a nighttime assessment when RLS symptom threshold is at its lowest. The purpose of this study was to elucidate the potential neural mechanisms underlying the circadian aspect of RLS symptom expression by assessing diurnal changes in DMN. METHODS: Fifteen drug-naïve subjects with idiopathic RLS and 15 age- and gender-matched healthy subjects had fMRI scans in the morning and evening. The DMN patterns were compared both for differences between morning and evening and between RLS and controls. RESULTS: RLS patients compared to the healthy controls showed significant differences in morning and evening DMN. In particular, RLS patients showed consistent increased connectivity in the parietal lobule in both the morning and evening. In contrast, connectivity in the thalamus was increased in the morning and reduced in the evening. In addition, there were negative correlations between thalamic connectivity and the Korean versions of the international RLS scale and the quality-of-life subscore. CONCLUSIONS: The results indicated diurnal disturbances of the DMN in RLS subjects are consistent with both the circadian rhythm and severity of RLS. The circadian expression of RLS may relate to changes in arousal cortical-activation thresholds occurring with diurnal changes in the thalamic circuits of the DMN.
OBJECTIVE:Restless legs syndrome (RLS) patients compared to controls have been found to have abnormal patterns in the default mode network (DMN) in the morning when symptom threshold is the highest and symptoms are least likely to occur. If these morning abnormalities in DMN are pertinent to disease expression, then similar or further detectable differences may be expected on a nighttime assessment when RLS symptom threshold is at its lowest. The purpose of this study was to elucidate the potential neural mechanisms underlying the circadian aspect of RLS symptom expression by assessing diurnal changes in DMN. METHODS: Fifteen drug-naïve subjects with idiopathic RLS and 15 age- and gender-matched healthy subjects had fMRI scans in the morning and evening. The DMN patterns were compared both for differences between morning and evening and between RLS and controls. RESULTS:RLSpatients compared to the healthy controls showed significant differences in morning and evening DMN. In particular, RLSpatients showed consistent increased connectivity in the parietal lobule in both the morning and evening. In contrast, connectivity in the thalamus was increased in the morning and reduced in the evening. In addition, there were negative correlations between thalamic connectivity and the Korean versions of the international RLS scale and the quality-of-life subscore. CONCLUSIONS: The results indicated diurnal disturbances of the DMN in RLS subjects are consistent with both the circadian rhythm and severity of RLS. The circadian expression of RLS may relate to changes in arousal cortical-activation thresholds occurring with diurnal changes in the thalamic circuits of the DMN.