title: Drug-induced stimulation and suppression of action monitoring in healthy volunteers.
abstract: BACKGROUND
  Action monitoring has been studied extensively by means of measuring the error-related negativity (ERN). The ERN is an event-related potential (ERP) elicited immediately after an erroneous response and is thought to originate in the anterior cingulate cortex (ACC). Although the ACC has a central role in the brain, only a few studies have been performed to investigate directly the effects of drugs on action monitoring. A recent theory argues that the mesencephalic dopamine system carries an error signal to the ACC, where it generates the ERN.
  
  
  METHODS
  ERPs and behavioral measurements were obtained from 12 healthy volunteers performing an Eriksen Flankers task. On each of the 4 test days, the stimulant D-amphetamine, the sedative lorazepam, the antidepressant mirtazapine, or a placebo was orally administered in a double-blind, four-way crossover design.
  
  
  RESULTS
  The indirect dopamine agonist amphetamine led to a strong enlargement of ERN amplitudes without affecting reaction times. Lorazepam and mirtazapine both showed slowing of responses, but only lorazepam led to reduced ERN amplitudes.
  
  
  CONCLUSIONS
  Administration of amphetamine leads to stimulated action monitoring, reflected in increased ERN amplitudes. This result provides evidence for dopaminergic involvement in action monitoring and is in line with differences in ERN amplitude found in neuropsychiatric disorders also suggesting dopaminergic involvement. The different effects for lorazepam and mirtazapine are probably caused by the neurobiological characteristics of these two types of sedation. Action monitoring is suppressed after administration of lorazepam, because the GABAergic pathways directly inhibit ACC functioning, whereas the histaminergic pathways of mirtazapine do not innervate the ACC directly.
authors.affiliation: Nijmegen Institute for Cognition and Information (NICI), Nijmegen, The Netherlands. ellendb@nici.kun.nl
authors.forename: Ellen R A
authors.initials: ER
authors.lastname: de Bruijn
authors.forename: Wouter
authors.initials: W
authors.lastname: Hulstijn
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Verkes
authors.forename: Gé S F
authors.initials: GS
authors.lastname: Ruigt
authors.forename: Bernard G C
authors.initials: BG
authors.lastname: Sabbe
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003913:Dextroamphetamine / Q000494:pharmacology; D004311:Double-Blind Method; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology
chemical_list: D008803:Mianserin; D000078785:Mirtazapine; D008140:Lorazepam; D003913:Dextroamphetamine