title: Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate.
abstract: BACKGROUND
  The basal ganglia play an important role in motor control, which is dependent on dopaminergic input. Preparation of a motor response has been associated with dopamine release in the basal ganglia, and response readiness may therefore serve as a pharmacodynamic marker of dopamine activity.
  
  
  METHODS
  We measured response readiness using the amplitude of the contingent negative variation (CNV), a slow negative shift in the electroencephalogram. The CNV is evoked in a paradigm in which a warning stimulus (S1) signals the occurrence of the imperative stimulus (S2) 4 s later, to which the participant has to respond. CNV was assessed in healthy volunteers after administration of placebo or 10, 20 or 40 mg of methylphenidate, a catecholamine re-uptake blocker which primarily enhances the synaptic concentration of dopamine and to a lesser extent also noradrenaline. In addition, participants filled out two visual analogue scales measuring subjective ratings of mood and alertness: Profile of Mood States and Bond and Lader.
  
  
  RESULTS
  Methylphenidate dose dependently increased CNV amplitude and decreased reaction times. Furthermore, participants reported improved mood, feeling more alert, vigorous and content and less angry and tired after methylphenidate.
  
  
  CONCLUSIONS
  These results indicate that dopamine availability increases response readiness as measured by the CNV paradigm. The CNV appears to be a good candidate biomarker for assessing changes in dopaminergic function by treatments that either directly or indirectly target the dopaminergic system.
authors: Department of Neuropsychology & Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, PO Box 616, 6200 MD Maastricht, the Netherlands. anke.linssen@maastrichtuniversity.nl
authors: Anke M W
authors: AM
authors: Linssen
authors: Eric F P M
authors: EF
authors: Vuurman
authors: Anke
authors: A
authors: Sambeth
authors: Stephane
authors: S
authors: Nave
authors: Will
authors: W
authors: Spooren
authors: Gabriel
authors: G
authors: Vargas
authors: Luca
authors: L
authors: Santarelli
authors: Wim J
authors: WJ
authors: Riedel
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