The Effects of Methylphenidate on the Neural Signatures of Sustained Attention

doi:10.1016/j.biopsych.2017.04.016

Biological Psychiatry

Volume 82, Issue 9, 1 November 2017, Pages 687-694

https://doi.org/10.1016/j.biopsych.2017.04.016 Get rights and content

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.

Section snippets

Participants

A total of 40 individuals (mean age = 24.3 years, SD = 5.6) participated in the study. All participants provided informed consent, in accordance with the ethics committee of The University of Queensland. Inclusion criteria were male, aged 18 to 45 years, right-handed, nonsmoking, no history of drug abuse, no current use of recreational drugs, no history of neuropsychiatric disorder, and not currently taking psychoactive medication. A consultant psychiatrist screened all participants using the

Behavioral Analysis

There was a significant effect of drug across all conditions (n = 33) on the proportion of targets detected (see Table 1), F_3,96 = 14.42, p < .0001, η_p² = .31. Pairwise comparisons showed that MPH increased the proportion of targets detected relative to PLA (p = .001), ATM (p = .0001), and CIT (p = .0001). ATM was not significantly different from PLA (p = .671). There was a marginal reduction of performance in the CIT condition compared with PLA (p = .033), but this did not survive Bonferroni

Discussion

This study examined the modulation of electrophysiological precursors of lapsing attention by MPH. Our findings demonstrate that MPH affects both the oscillatory dynamics in the alpha band during sustained attention and shorter-term ERP signals in the period before and during target processing. MPH acts to avert lapses of attention and time-on-task performance decrements by reducing maladaptive neural synchronization in the alpha band over a broader time scale, indicative of a change in

Acknowledgments and Disclosures

This work was supported by Grant No. 569532 from the National Health and Medical Research Council of Australia (to MAB) and Young Investigator Grant No. 22457 from the Brain and Behavior Research Foundation (to RGO). MAB is supported by a Future Fellowship No. FT130101488 from the Australian Research Council. This project was also supported by Marie Curie International Research Staff Exchange Scheme No. 612681 under the European Commission FP7 (to RGO and MAB).

We thank Zoltan Dienes for his

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⁴: MAB and RGO contributed equally to this work.

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