Event-related potentials reflect impaired temporal interval learning following haloperidol administration.

BACKGROUND: Signals carried by the mesencephalic dopamine system and conveyed to anterior cingulate cortex are critically implicated in probabilistic reward learning and performance monitoring. A common evaluative mechanism purportedly subserves both functions, giving rise to homologous medial frontal negativities in feedback- and response-locked event-related brain potentials (the feedback-related negativity (FRN) and the error-related negativity (ERN), respectively), reflecting dopamine-dependent prediction error signals to unexpectedly negative events. Consistent with this model, the dopamine receptor antagonist, haloperidol, attenuates the ERN, but effects on FRN have not yet been evaluated. METHODS: ERN and FRN were recorded during a temporal interval learning task (TILT) following randomized, double-blind administration of haloperidol (3 mg; n = 18), diphenhydramine (an active control for haloperidol; 25 mg; n = 20), or placebo (n = 21) to healthy controls. Centroparietal positivities, the Pe and feedback-locked P300, were also measured and correlations between ERP measures and behavioral indices of learning, overall accuracy, and post-error compensatory behavior were evaluated. We hypothesized that haloperidol would reduce ERN and FRN, but that ERN would uniquely track automatic, error-related performance adjustments, while FRN would be associated with learning and overall accuracy. RESULTS: As predicted, ERN was reduced by haloperidol and in those exhibiting less adaptive post-error performance; however, these effects were limited to ERNs following fast timing errors. In contrast, the FRN was not affected by drug condition, although increased FRN amplitude was associated with improved accuracy. Significant drug effects on centroparietal positivities were also absent. CONCLUSIONS: Our results support a functional and neurobiological dissociation between the ERN and FRN.

Haloperidol impairs learning and error-related negativity in humans.

Humans are able to monitor their actions for behavioral conflicts and performance errors. Growing evidence suggests that the error-related negativity (ERN) of the event-related cortical brain potential (ERP) may index the functioning of this response monitoring system and that the ERN may depend on dopaminergic mechanisms. We examined the role of dopamine in ERN and behavioral indices of learning by administering either 3 mg of the dopamine antagonist (DA) haloperidol (n = 17); 25 mg of diphenhydramine (n = 16), which has a similar CNS profile but without DA properties; or placebo (n = 18) in a randomized, double-blind manner to healthy volunteers. Three hours after drug administration, participants performed a go/no-go Continuous Performance Task, the Eriksen Flanker Task, and a learning-dependent Time Estimation Task. Haloperidol significantly attenuated ERN amplitudes recorded during the flanker task, impaired learning of time intervals, and tended to cause more errors of commission, compared to placebo, which did not significantly differ from diphenhydramine. Drugs had no significant effects on the stimulus-locked P1 and N2 ERPs or on behavioral response latencies, but tended to affect post-error reaction time (RT) latencies in opposite ways (haloperidol decreased and diphenhydramine increased RTs). These findings support the hypothesis that the DA system is involved in learning and the generation of the ERN.