Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate

Psychopharmacology (Berl). 2011 Dec;218(3):533-42. doi: 10.1007/s00213-011-2345-x. Epub 2011 May 20.


Rationale: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism
  • Contingent Negative Variation / drug effects*
  • Cross-Over Studies
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electroencephalography
  • Humans
  • Male
  • Methylphenidate / administration & dosage
  • Methylphenidate / pharmacology*
  • Norepinephrine / metabolism
  • Young Adult


  • Dopamine Uptake Inhibitors
  • Methylphenidate
  • Dopamine
  • Norepinephrine