title: Different patterns of spontaneous brain activity between tremor-dominant and postural instability/gait difficulty subtypes of Parkinson's disease: a resting-state fMRI study.
abstract: OBJECTIVE
  Postural instability/gait difficulty (PIGD) and tremor-dominant (TD) subtypes of Parkinson's disease (PD) show different clinical manifestations; however, their underlying neural substrates remain incompletely understood. This study aimed at investigating the subtype-specific patterns of spontaneous brain activity in PD.
  
  
  METHODS
  Thirty-one patients with PD (12 TD/19 PIGD) and 22 healthy gender- and age-matched controls were recruited. Resting-state functional magnetic resonance imaging data were collected, and amplitude of low-frequency fluctuations (ALFF) was measured. Voxelwise one-way analysis of covariance and post hoc analyses of ALFF were performed among the three groups, with age and gender as covariates (levodopa daily dosage and gray matter volume as additional covariates for validation analysis). Correlations of clinical variables (e.g., disease duration and PIGD/tremor subscale score) with ALFF values were examined.
  
  
  RESULTS
  Compared with controls, patients with TD exhibited higher ALFF in the right cerebellar posterior lobe and patients with PIGD exhibited lower ALFF in the bilateral putamen and cerebellar posterior lobe, and higher values primarily in several cortical areas including the inferior and superior temporal gyrus, superior frontal, and parietal gyrus. Compared with patients with PIGD, patients with TD had higher ALFF in the bilateral putamen and the cerebellar posterior lobe, as well as lower ALFF in the bilateral temporal gyrus and the left superior parietal lobule. In all patients, ALFF in the bilateral cerebellar posterior lobe positively correlated with tremor score and ALFF in the bilateral putamen negatively correlated with PIGD score.
  
  
  CONCLUSIONS
  Different patterns of spontaneous neural activity in the cerebellum and putamen may underlie the neural substrate of PD motor subtypes.
authors.affiliation: Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China.
authors.forename: Zhi-Jiang
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Fang
authors.affiliation: Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Gao
authors.affiliation: Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Ma
authors.affiliation: Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.|Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.|Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Hou
authors.affiliation: Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.|Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.
authors.forename: Jia-Rong
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.|Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D010300:Parkinson Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D012146:Rest; D014202:Tremor / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Amplitude of low-frequency fluctuations (ALFF); Parkinson's disease; Postural instability/gait difficulty (PIGD); Resting-state fMRI; Tremor