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.
- Contingent negative variation
- Event-related potentials
- Response preparation
- BASAL GANGLIA
- HUMAN BRAIN
- ORAL METHYLPHENIDATE
Linssen, A. M. W., Vuurman, E. F. P. M., Sambeth, A., Nave, S., Spooren, W., Vargas, G., Santarelli, L., & Riedel, W. J. (2011). Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate. Psychopharmacology, 218(3), 533-542. https://doi.org/10.1007/s00213-011-2345-x