title: Mapping intrinsic functional brain changes and repetitive transcranial magnetic stimulation neuromodulation in idiopathic restless legs syndrome: a resting-state functional magnetic resonance imaging study.
abstract: OBJECTIVE
  The objectives of this study were, first, to explore differences in brain activity between normal people and idiopathic restless legs syndrome (RLS) patients during asymptomatic periods; and, second, to determine whether administering repetitive transcranial magnetic stimulation (rTMS) to specific cortical regions would reverse any observed differences in brain activity and alleviate patient symptoms.
  
  
  METHODS
  Fifteen idiopathic RLS patients (nine drug-naive patients) and 14 gender- and age-matched healthy controls were enrolled. Resting-state functional magnetic resonance imaging was used to measure the amplitude of low-frequency fluctuations (ALFF) in spontaneous brain activity during asymptomatic periods. Seven patients received high-frequency (5 Hz) rTMS directed toward the leg area of the primary motor cortex. Scores on the International Restless Legs Syndrome Study Group (IRLSSG) Rating Scale and ALFF values were measured before and after treatment.
  
  
  RESULTS
  Compared with healthy controls, RLS patients showed lower ALFF in the sensorimotor and visual processing regions, and higher ALFF in the insula, parahippocampal and hippocampal gyri, left posterior parietal areas, and brainstem. These results were largely conserved when only drug-naive patients were considered. After rTMS treatment, ALFF in several sensorimotor and visual regions were significantly elevated and IRLSSG Rating Scale scores decreased, indicating improved RLS symptoms.
  
  
  CONCLUSIONS
  High-frequency rTMS delivered to the leg area of the primary motor cortex may raise functional activity in the sensorimotor and occipital regions, leading to improve symptoms in RLS patients. These results provide novel insight into RLS pathophysiology and suggest a potential mechanism for rTMS therapy in idiopathic RLS patients.
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Neuromodulation, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Functional Neurology, Lu He Teaching Hospital, Capital Medical University, Beijing, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Radiology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
authors.forename: Yicong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China. Electronic address: yong.he@bnu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China; Beijing Key Laboratory of Neuromodulation, Beijing, China. Electronic address: wangyuping01@sina.cn.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000502:physiology; D009778:Occipital Lobe / Q000503:physiopathology; D012016:Reference Values; D012148:Restless Legs Syndrome / Q000503:physiopathology* / Q000628:therapy*; D066191:Sensorimotor Cortex / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation
chemical_list: D018377:Neurotransmitter Agents
keywords: ALFF; Neuromodulation; Pathophysiology; RLS; Resting-state functional MRI; rTMS