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

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

Author information

1
Institute of Neurogenetics, University of Luebeck, Germany; Department of Neurology, University of Luebeck, Germany.
2
Institute of Neurogenetics, University of Luebeck, Germany.
3
Center for Biomedicine, European Academy of Bolzano, Bolzano, Italy.
4
Division of Neurology, Krembil Neuroscience Centre and Toronto Western Research Institute, University Health Network, Toronto, Canada.
5
Institute of Neurogenetics, University of Luebeck, Germany. Electronic address: alexander.muenchau@neuro.uni-luebeck.de.

Abstract

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

PMID:
27843055
DOI:
10.1016/j.clinph.2016.10.007
[Indexed for MEDLINE]

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