Cortical response to levodopa in Parkinson's disease patients with dyskinesias

Eur J Neurosci. 2018 Sep;48(6):2362-2373. doi: 10.1111/ejn.14114. Epub 2018 Sep 3.


Levodopa-induced dyskinesias are a common and disabling side effect of dopaminergic therapy in Parkinson's disease, but their neural mechanisms in vivo are still poorly understood. Besides striatal pathology, the importance of cortical dysfunction has been increasingly recognized. The supplementary motor area in particular, may have a relevant role in dyskinesias onset given its involvement in endogenously generated actions. The aim of the present study was to investigate the levodopa-related cortical excitability changes along with the emergence of levodopa-induced peak-of-dose dyskinesias in subjects with Parkinson's disease. Thirteen patients without dyskinesias and ten with dyskinesias received 200/50 mg fast-acting oral levodopa/benserazide following overnight withdrawal (12 hr) from their dopaminergic medication. We targeted transcranial magnetic stimulation to the supplementary motor area, ipsilateral to the most dopamine-depleted striatum defined with single-photon emission computed tomography with [123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane, and recorded transcranial magnetic stimulation-evoked potentials with high-density electroencephalography before and at 30, 60, and 180 min after levodopa/benserazide intake. Clinical improvement from levodopa/benserazide paralleled the increase in cortical excitability in both groups. Subjects with dyskinesias showed higher fluctuation of cortical excitability in comparison to non-dyskinetic patients, possibly reflecting dyskinetic movements. Together with endogenous brain oscillation, levodopa-related dynamics of brain state could influence the therapeutic response of neuromodulatory interventions.

Keywords: Parkinson's disease; cortical excitability; dyskinesias; electroencephalography; supplementary motor area; transcranial magnetic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / therapeutic use*
  • Benserazide / pharmacology*
  • Brain / drug effects
  • Brain / physiopathology
  • Drug Combinations
  • Dyskinesia, Drug-Induced / drug therapy
  • Electroencephalography / methods
  • Female
  • Humans
  • Levodopa / pharmacology*
  • Male
  • Middle Aged
  • Motor Cortex / physiopathology
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Transcranial Magnetic Stimulation / methods


  • Antiparkinson Agents
  • Drug Combinations
  • benserazide, levodopa drug combination
  • Levodopa
  • Benserazide