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.
RCT Entities:
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.
Authors: M J Millan; A Newman-Tancredi; V Audinot; D Cussac; F Lejeune; J P Nicolas; F Cogé; J P Galizzi; J A Boutin; J M Rivet; A Dekeyne; A Gobert Journal: Synapse Date: 2000-02 Impact factor: 2.562
Authors: Ellen R A de Bruijn; Bernard G C Sabbe; Wouter Hulstijn; Gé S F Ruigt; Robbert J Verkes Journal: Brain Res Date: 2006-02-24 Impact factor: 3.252
Authors: Sarah E Forster; Patrick Zirnheld; Anantha Shekhar; Stuart R Steinhauer; Brian F O'Donnell; William P Hetrick Journal: Psychopharmacology (Berl) Date: 2017-06-10 Impact factor: 4.530
Authors: Iris Schutte; Peter K H Deschamps; Peter N van Harten; J Leon Kenemans Journal: Psychopharmacology (Berl) Date: 2020-04-20 Impact factor: 4.530