Abnormal premotor-motor interaction in heterozygous Parkin- and Pink1 mutation carriers

Clin Neurophysiol. 2017 Jan;128(1):275-280. doi: 10.1016/j.clinph.2016.10.007. Epub 2016 Oct 26.


Objectives: 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.

Conclusion: Premotor-motor excitability changes are part of the cortical reorganization in asymptomatic heterozygous Parkin- and PINK1 mutation carriers.

Significance: These subjects offer opportunities to delineate motor network adaptation in pre-symptomatic Parkinsonism.

Keywords: Genetics; Motor cortex; Parkinsonism; Premotor cortex; TMS.

MeSH terms

  • Aged
  • Electromyography / methods*
  • Female
  • Heterozygote*
  • Humans
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology*
  • Mutation / genetics*
  • Protein Kinases / genetics*
  • Transcranial Magnetic Stimulation / methods
  • Ubiquitin-Protein Ligases / genetics*


  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase