title: Preclinical and clinical neural network changes in SCA2 parkinsonism.
abstract: BACKGROUND
  The pathophysiological changes before the presentation of clinical symptoms in parkinsonism are unclear. In this study, we investigated neural network modulations in persons in the preclinical stage of familial parkinsonism, and how the network interactions change at the clinical stage.
  
  
  METHODS
  We performed functional MRI in a family with SCA2 mutation, including 9 asymptomatic carriers and 10 mutation carriers with parkinsonian symptoms. Functional connectivity from the posterior putamen bilaterally and rostral supplementary motor area was used to explore network interactions in the subjects.
  
  
  RESULTS
  Both the asymptomatic carriers and patients had decreased connectivity within the basal ganglia-thalamus-cortical motor loop compared to controls. The asymptomatic carriers showed extensively increased connectivity compared to controls, including the cortico-cortical motor, cortico-cerebellar, cortico-brainstem, and part of the basal ganglia-thalamus-cortical motor circuits. In contrast, the connectivity of most of these networks was decreased in the patients. These abnormalities were relatively normalized after levodopa administration.
  
  
  CONCLUSIONS
  In the preclinical stage of SCA2 parkinsonism, the connectivity of a part of the basal ganglia motor loop is weakened as a consequence of dopaminergic deficits; meanwhile, the connectivity of other large-scale brain networks is strengthened presumably to compensate for the dysfunction of the basal ganglia to maintain brain function in the early stage of dopaminergic deficits. The simultaneous effects of progressive disruption of basal ganglia motor circuits and failure of compensatory mechanisms as dopaminergic dysfunction progresses may contribute to the onset of clinical symptoms.
authors.affiliation: Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wang
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zang
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
mesh_terms: D000328:Adult; D000067528:Ataxins; D001921:Brain / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D009434:Neural Pathways / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000235:genetics / Q000503:physiopathology*
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins