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Monoaminergic modulation of behavioural and electrophysiological indices of error processing

Abstract

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.

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Acknowledgments

This work was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC) (569532) to MAB. MAB is supported by a Career Development Award from the NHMRC, Australia. We would like to thank the Wesley Hospital Pharmacy for dispensing the drugs associated with this project.

Conflict of interest

Both LSN and MAB have received reimbursement from Lilly Pharmaceuticals for conference travel expenses and for speaking at conferences. The author MAB has received speaker's fees from Janssen-Cilag. The author LSN has received speaker's fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim and Janssen-Cilag. The authors JJMB, RGO and AJD report no biomedical financial interests or potential conflicts of interest.

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Correspondence to Mark A. Bellgrove.

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Barnes, J.J.M., O’Connell, R.G., Nandam, L.S. et al. Monoaminergic modulation of behavioural and electrophysiological indices of error processing. Psychopharmacology 231, 379–392 (2014). https://doi.org/10.1007/s00213-013-3246-y

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Keywords

  • Atomoxetine
  • Citalopram
  • Dopamine
  • Error positivity
  • Error processing
  • Error-related negativity
  • Methylphenidate
  • Noradrenaline
  • Performance monitoring
  • Serotonin