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Drug-induced stimulation and suppression of action monitoring in healthy volunteers
Abstract
Rationale 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.
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In the citing paper
“five studies measured the effect of AMP on inhibitory or impulse control using Stop‐Signal Task (SST) or Eriksen Flanker task (EFT) (de Bruijn et al., 2004; de Wit et al., 2002; Dolder et al., 2018; Fillmore et al., 2005; Ilieva et al., 2013) and only two studies found main effects (de Wit et al., 2002; Dolder et al., 2018).”
From Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits (2023) · cites this paper as de Bruijn et al., 2004
In the citing paper
“This is contradictory to evidence from adult studies showing that stimulants like Mph boost the response-locked ERN amplitude (De Bruijn et al., 2004; De Bruijn et al., 2005).”
From Error and feedback processing in children with ADHD and children with Autistic Spectrum Disorder: An EEG event-related potential study (2008) · cites this paper as De Bruijn et al., 2004
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Metadata
- Authors
- de Bruijn, E. R. A., Hulstijn, W., Verkes, R. J., Ruigt, G. S. F., & Sabbe, B. G. C.
- Affiliations
- Radboud University Nijmegen (NL)
- Organon (Netherlands) (NL)
- Venue
- Psychopharmacology
- Published
- 2004-05-15
- Volume
- 177
- Issue
- 1-2
- Pages
- 151-160
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2116254744
- Cited by
- 282
- References
- 49
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 6 · 2021: 10 · 2020: 14 · 2019: 10 · 2018: 11 · 2017: 7 · 2016: 12 · 2015: 18 · 2014: 12 · 2013: 17 · 2012: 14
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Arts and Humanities › Philosophy › Free Will and Agency
- Keywords
- action monitoring, error-related negativity, anterior cingulate cortex, dopamine, amphetamine, lorazepam, mirtazapine, flanker task, response inhibition, GABAergic inhibition, stimulants, sedatives
- MeSH terms
- Mirtazapine, Adult, Cerebral Cortex, Dextroamphetamine, Double-Blind Method, Evoked Potentials, Female, Gyrus Cinguli, Humans, Lorazepam, Male, Mianserin, Psychomotor Performance, Reaction Time, Cross-Over Studies
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