Drug-induced stimulation and suppression of action monitoring in healthy volunteers

Authors: Bruijn, Ellen¹; Hulstijn, Wouter²; Verkes, Robbert³; Ruigt, Gé⁴; Sabbe, Bernard⁵

Source: Psychopharmacology, Volume 177, Numbers 1-2, December 2004 , pp. 151-160(10)

Publisher: Springer

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Abstract:

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.

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.

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.

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.

Keywords: Action monitoring; Error-related negativity (ERN); Anterior cingulate cortex (ACC); Dopamine; Sedation; d-Amphetamine; Lorazepam; Mirtazapine

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s00213-004-1915-6

Affiliations: 1: Nijmegen Institute for Cognition and Information (NICI), Nijmegen, The Netherlands, Email: ellendb@nici.kun.nl 2: Nijmegen Institute for Cognition and Information (NICI), Nijmegen, The Netherlands, 3: Unit for Clinical Psychopharmacology and Neuropsychiatry, University Medical Center Nijmegen, Nijmegen, The Netherlands, 4: Clinical Pharmacology Department Organon, Oss, The Netherlands, 5: Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium,

Publication date: 2004-12-01

Drug-induced stimulation and suppression of action monitoring in healthy volunteers

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