title: Non-homogeneous effect of levodopa on inhibitory circuits in Parkinson's disease and dyskinesia.
abstract: BACKGROUND
  Levodopa-induced dyskinesia in patients with Parkinson's disease (PD) has been shown to be associated with an abnormal plasticity in the motor cortex. We investigated whether changes in the excitability of inhibitory and excitatory motor circuits could underlie maladaptive mechanisms associated with dyskinesia.
  
  
  METHODS
  Using single and paired transcranial magnetic stimulation (TMS), we studied motor threshold, silent period (SP) duration, intracortical facilitation (ICF), short intracortical inhibition (SICI) and low- and high-intensity long intracortical inhibition (LICI) in 10 dyskinetic and 10 non-dyskinetic patients, matched for disease and treatment duration, before (OFF state) and after (ON state) levodopa, and in 10 healthy controls.
  
  
  RESULTS
  In the OFF state, the two groups of patients showed similar motor cortex excitability with a reduced SICI compared to controls. LICI was weaker and increasing stimulation intensity had a lower effect on SP duration in dyskinetic patients than in controls. In dyskinetic patients, in contrast to non-dyskinetic patients, levodopa failed to increase SICI and SP duration, and potentiated to a lesser extent the effect of increasing the stimulation intensity on LICI. Although levodopa improved motor symptoms to a similar extent in both dyskinetic and non-dyskinetic patients, it failed to activate effectively the excitability of the inhibitory systems in dyskinetic patients.
  
  
  CONCLUSIONS
  These findings suggest that dyskinesia is associated with an abnormal effect of levodopa on cortical motor inhibitory circuits.
authors.affiliation: INSERM, CIC 0004, Nantes, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Barbin
authors.forename: Christophe
authors.initials: C
authors.lastname: Leux
authors.forename: Paul
authors.initials: P
authors.lastname: Sauleau
authors.forename: Claire
authors.initials: C
authors.lastname: Meyniel
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.forename: Yann
authors.initials: Y
authors.lastname: Pereon
authors.forename: Philippe
authors.initials: P
authors.lastname: Damier
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects* / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa