Monoaminergic modulation of behavioural and electrophysiological indices of error processing

• Published in: Psychopharmacology Vol. 231; no. 2; pp. 379 - 392
• Main Authors: Barnes, Jessica J. M., O’Connell, Redmond G., Nandam, L. Sanjay, Dean, Angela J., Bellgrove, Mark A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2014; Springer; Springer Nature B.V
• Subjects: Adrenergic Uptake Inhibitors - pharmacology; Analysis; Atomoxetine Hydrochloride; Behavioral psychology; Biomedical and Life Sciences; Biomedicine; Catecholamines; Citalopram - pharmacology; Cross-Over Studies; Dopamine; Dopamine Uptake Inhibitors - pharmacology; Double-Blind Method; Errors; Evoked Potentials - drug effects; Executive Function - drug effects; Female; Humans; Male; Methylphenidate - pharmacology; Neuropsychological Tests; Neurosciences; Neurotransmitters; Original Investigation; Pharmacology/Toxicology; Propylamines - pharmacology; Psychiatry; Psychomotor Performance - drug effects; Psychopharmacology; Reaction Time - drug effects; Serotonin; Serotonin Uptake Inhibitors - pharmacology; Studies; Young Adult; Dopamine; Atomoxetine; Serotonin; Error positivity; Error-related negativity; Noradrenaline; Performance monitoring; Error processing; Methylphenidate; Citalopram
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-3246-y

Rationale Error processing is a critical executive function that is impaired in a large number of clinical populations. Although the neural underpinnings of this function have been investigated for decades and critical error-related components in the human electroencephalogram (EEG), such as the error-related negativity (ERN) and the error positivity (Pe), have been characterised, our understanding of the relative contributions of key neurotransmitters to the generation of these components remains limited. Objectives The current study sought to determine the effects of pharmacological manipulation of the dopamine, noradrenaline and serotonin neurotransmitter systems on key behavioural and event-related potential correlates of error processing. Methods A randomised, double-blinded, placebo-controlled, crossover design was employed. Monoamine levels were manipulated using the clinically relevant drugs methylphenidate, atomoxetine and citalopram, in comparison to placebo. Under each of the four drug conditions, participants underwent EEG recording while performing a flanker task. Results Only methylphenidate produced significant improvement in performance accuracy, which was without concomitant slowing of reaction time. Methylphenidate also increased the amplitude of an early electrophysiological index of error processing, the ERN. Citalopram increased the amplitude of the correct-response negativity, another component associated with response processing. Conclusions The effects of methylphenidate in this study are consistent with theoretical accounts positing catecholamine modulation of error monitoring. Our data suggest that enhancing catecholamine function has the potential to remediate the error-monitoring deficits that are seen in a wide range of psychiatric conditions.