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

• Published in: Clinical neurophysiology Vol. 128; no. 1; pp. 275 - 280
• Main Authors: Weissbach, Anne, Bäumer, Tobias, Pramstaller, Peter P., Brüggemann, Norbert, Tadic, Vera, Chen, Robert, Klein, Christine, Münchau, Alexander
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2017
• Subjects: Aged; Electromyography - methods; Female; Genetics; Heterozygote; Humans; Male; Middle Aged; Motor cortex; Motor Cortex - physiopathology; Mutation - genetics; Neurology; Parkinsonism; Premotor cortex; Protein Kinases - genetics; TMS; Transcranial Magnetic Stimulation - methods; Ubiquitin-Protein Ligases - genetics; M1; PMd; SMA; AMT; FDI; Parkinsonism; fMRI; Motor cortex; AMC; DRD; RMT; MEP; Genetics; Premotor cortex; TMS; iPD; EMG; resting motor thresholds; dopa-responsive dystonia; motor-evoked potential; asymptomatic, heterozygous Parkin and PINK1 mutation carriers; transcranial magnetic stimulation; active motor thresholds; primary motor cortex; first dorsal interosseus muscles; supplementary motor area; electromyography; functional magnetic resonance imaging; idiopathic Parkinsonism; dorsal premotor cortex
• ISSN: 1388-2457; 1872-8952
• DOI: 10.1016/j.clinph.2016.10.007

•Asymptomatic heterozygous Parkin/PINK1 mutation carriers show altered premotor–motor inhibition.•A single l-dopa administration could partly reverse this alteration.•These mutation carriers can serve as in vivo models to study pre-symptomatic stages of Parkinsonism. 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. 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. 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. Premotor–motor excitability changes are part of the cortical reorganization in asymptomatic heterozygous Parkin- and PINK1 mutation carriers. These subjects offer opportunities to delineate motor network adaptation in pre-symptomatic Parkinsonism.