The Effects of Methylphenidate on the Neural Signatures of Sustained Attention

Paul M Dockree; Jessica J Barnes; Natasha Matthews; Angela J Dean; Rafael Abe; L Sanjay Nandam; Simon P Kelly; Mark A Bellgrove; Redmond G O'Connell

doi:10.1016/j.biopsych.2017.04.016

The Effects of Methylphenidate on the Neural Signatures of Sustained Attention

Biol Psychiatry. 2017 Nov 1;82(9):687-694. doi: 10.1016/j.biopsych.2017.04.016. Epub 2017 May 10.

Authors

Paul M Dockree¹, Jessica J Barnes², Natasha Matthews², Angela J Dean², Rafael Abe³, L Sanjay Nandam², Simon P Kelly⁴, Mark A Bellgrove⁵, Redmond G O'Connell⁶

Affiliations

¹ School of Psychology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Electronic address: dockreep@tcd.ie.
² Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
³ School of Psychological Sciences and Monash Institute for Cognitive and Clinical Neurosciences, Monash University, Melbourne, Australia.
⁴ School of Electrical and Electronic Engineering, University College Dublin, Dublin, Ireland.
⁵ School of Psychology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; School of Psychological Sciences and Monash Institute for Cognitive and Clinical Neurosciences, Monash University, Melbourne, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
⁶ School of Psychology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; School of Psychological Sciences and Monash Institute for Cognitive and Clinical Neurosciences, Monash University, Melbourne, Australia.

PMID: 28599833
DOI: 10.1016/j.biopsych.2017.04.016

Abstract

Background: Although it is well established that methylphenidate (MPH) enhances sustained attention, the neural mechanisms underpinning this improvement remain unclear. We examined how MPH influenced known electrophysiological precursors of lapsing attention over different time scales.

Methods: We measured the impact of MPH, compared with placebo, on behavioral and electrocortical markers while healthy adults (n = 40) performed a continuous monitoring paradigm designed to elicit attentional lapses.

Results: MPH led to increased rates of target detection, and electrophysiological analyses were conducted to identify the mechanisms underlying these improvements. Lapses of attention were reliably preceded by progressive increases in alpha activity that emerged over periods of several seconds. MPH led to an overall suppression of alpha activity across the entire task but also diminished the frequency of these maladaptive pretarget increases through a reduction of alpha variability. A drug-related linear increase in the amplitude of the frontal P3 event-related component was also observed in the pretarget timeframe (3 or 4 seconds). Furthermore, during immediate target processing, there was a significant increase in the parietal P3 amplitude with MPH, indicative of enhanced perceptual evidence accumulation underpinning target detection. MPH-related enhancements occurred without significant changes to early visual processing (visual P1 and 25-Hz steady-state visual evoked potential).

Conclusions: MPH serves to reduce maladaptive electrophysiological precursors of lapsing attention by acting selectively on top-down endogenous mechanisms that support sustained attention and target detection with no significant effect on bottom-up sensory excitability. These findings offer candidate markers to monitor the therapeutic efficacy of psychostimulants or to predict therapeutic responses.

Keywords: EEG oscillations; Inattention; Perceptual decision making; Psychostimulants; Ritalin; Time-on-task decrement.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Attention / drug effects*
Brain Waves / drug effects*
Central Nervous System Stimulants / administration & dosage
Central Nervous System Stimulants / pharmacology*
Cross-Over Studies
Double-Blind Method
Evoked Potentials / drug effects*
Humans
Male
Methylphenidate / administration & dosage
Methylphenidate / pharmacology*
Psychomotor Performance / drug effects*
Young Adult

Substances

Central Nervous System Stimulants
Methylphenidate