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

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Abstract

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.

    Research areas

  • Contingent negative variation, Methylphenidate, Event-related potentials, Response preparation, Dopamine, BASAL GANGLIA, HUMAN BRAIN, ORAL METHYLPHENIDATE, CNV, POTENTIALS, PHARMACOKINETICS, ANTICIPATION, RESPONSES, MOVEMENT, DIAZEPAM
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Details

Original languageEnglish
Pages (from-to)533-542
Number of pages10
JournalPsychopharmacology
Volume218
Issue number3
DOIs
Publication statusPublished - Dec 2011