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

Sarah E. Forster, Patrick Zirnheld, Anantha Shekhar, Stuart R. Steinhauer, Brian F. O’Donnell, William P. Hetrick

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2545-2562
Number of pages18
JournalPsychopharmacology
Volume234
Issue number17
DOIs
StatePublished - Sep 1 2017

Keywords

  • Antipsychotic
  • Control
  • Dopamine
  • ERPs
  • Learning
  • Timing

ASJC Scopus subject areas

  • Pharmacology

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