title: Abnormal premotor-motor interaction in heterozygous Parkin- and Pink1 mutation carriers.
abstract: OBJECTIVE
  Mutations in the Parkin and PINK1 gene account for the majority of autosomal recessive early-onset Parkinson cases. There is increasing evidence that clinically asymptomatic subjects with single heterozygous mutations have a latent nigrostriatal dopaminergic deficit and could be taken as in vivo model of pre-symptomatic phase of Parkinsonism.
  
  
  METHODS
  We charted premotor-motor excitability changes as compensatory mechanisms for subcortical dopamine depletions using transcranial magnetic stimulation by applying magnetic resonance-navigated premotor-motor cortex conditioning in 15 asymptomatic, heterozygous Parkin and PINK1 mutation carriers (2 female; mean age 53±8years) and 16 age- and sex-matched controls (5 female; mean age 57±9years). Participants were examined at baseline and after acute l-dopa challenge.
  
  
  RESULTS
  There were l-dopa and group specific effects during premotor-motor conditioning at an interstimulus interval of 6ms indicating a normalisation of premotor-motor interactions in heterozygous Parkin and PINK1 mutation carriers after l-dopa intake. Non-physiologically high conditioned MEP amplitudes at this interval in mutation carriers decreased after l-dopa intake but increased in controls.
  
  
  CONCLUSIONS
  Premotor-motor excitability changes are part of the cortical reorganization in asymptomatic heterozygous Parkin- and PINK1 mutation carriers.
  
  
  CONCLUSIONS
  These subjects offer opportunities to delineate motor network adaptation in pre-symptomatic Parkinsonism.
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Germany; Department of Neurology, University of Luebeck, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Weissbach
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bäumer
authors.affiliation: Center for Biomedicine, European Academy of Bolzano, Bolzano, Italy.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Germany; Department of Neurology, University of Luebeck, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Brüggemann
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Germany; Department of Neurology, University of Luebeck, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Tadic
authors.affiliation: Division of Neurology, Krembil Neuroscience Centre and Toronto Western Research Institute, University Health Network, Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Germany. Electronic address: alexander.muenchau@neuro.uni-luebeck.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Münchau
mesh_terms: D000368:Aged; D004576:Electromyography / Q000379:methods*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
keywords: Genetics; Motor cortex; Parkinsonism; Premotor cortex; TMS