title: Sensorimotor integration is abnormal in asymptomatic Parkin mutation carriers: a TMS study.
abstract: BACKGROUND
  In patients with Parkinson disease (PD), transcranial magnetic stimulation (TMS) studies have consistently demonstrated a reduced inhibitory tone in the sensorimotor cortex. It remains unclear whether this is related to motor symptoms or represents adaptive compensatory changes to degeneration of dopaminergic neurons. Here we used short-interval afferent inhibition after digital stimulation (dSAI) and intracortical paired-pulse inhibition and facilitation to probe intracortical sensorimotor excitability in clinically asymptomatic carriers of a single mutant Parkin allele who have a latent nigrostriatal dopaminergic dysfunction.
  
  
  METHODS
  Nine heterozygous mutation carriers and nine healthy controls were investigated. For dSAI testing, electrical pulses were applied to the right index finger followed by TMS pulses over the left motor cortex at interstimulus intervals (ISI) of 25, 30, and 40 msec. Intracortical paired-pulse excitability was tested at ISIs of 2 to 15 msec.
  
  
  RESULTS
  dSAI was reduced at an ISI of 25 msec in carriers of a single mutant Parkin allele, whereas paired-pulse TMS was normal.
  
  
  CONCLUSIONS
  The relative decrease in sensorimotor inhibition may be a direct consequence of the Parkin mutation or represent adaptive changes at the cortical level in response to a subcortical dysfunction, but is not caused by motor symptoms.
authors.affiliation: Department of Neurology, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. baeumer@uke.de
authors.forename: T
authors.initials: T
authors.lastname: Bäumer
authors.forename: P P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: H R
authors.initials: HR
authors.lastname: Siebner
authors.forename: S
authors.initials: S
authors.lastname: Schippling
authors.forename: J
authors.initials: J
authors.lastname: Hagenah
authors.forename: M
authors.initials: M
authors.lastname: Peller
authors.forename: C
authors.initials: C
authors.lastname: Gerloff
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Münchau
mesh_terms: D000328:Adult; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D009154:Mutation; D010300:Parkinson Disease / Q000503:physiopathology*; D013003:Somatosensory Cortex / Q000503:physiopathology*; D013647:Task Performance and Analysis; D050781:Transcranial Magnetic Stimulation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein