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

Francesco Turco, Andrea Canessa, Chiara Olivieri, Nicoló G. Pozzi, Chiara Palmisano, Gabriele Arnulfo, Giorgio Marotta, Jens Volkmann, Gianni Pezzoli, Ioannis U. Isaias

Research output: Contribution to journalArticle

Abstract

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 [123I]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.

Original languageEnglish
Pages (from-to)2362-2373
JournalEuropean Journal of Neuroscience
Volume48
Issue number6
DOIs
Publication statusPublished - 2018

Keywords

  • cortical excitability
  • dyskinesias
  • electroencephalography
  • Parkinson's disease
  • supplementary motor area
  • transcranial magnetic stimulation

ASJC Scopus subject areas

  • Neuroscience(all)

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    Turco, F., Canessa, A., Olivieri, C., Pozzi, N. G., Palmisano, C., Arnulfo, G., Marotta, G., Volkmann, J., Pezzoli, G., & Isaias, I. U. (2018). Cortical response to levodopa in Parkinson's disease patients with dyskinesias. European Journal of Neuroscience, 48(6), 2362-2373. https://doi.org/10.1111/ejn.14114