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The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD

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Abstract

We examined the effect of a single dose of methylphenidate (MPH) on whole brain functional connectivity, assessed using resting state functional MRI (rsfMRI), in young people with ADHD. 16 young people with ADHD participated in two rsfMRI scans in a randomized, placebo-controlled study with an acute dose of MPH (20 mg). 15 typically developing controls also performed the task under placebo conditions. The network-based statistic (NBS) was used to identify differential connectivity patterns between the MPH and placebo conditions in the ADHD group. Mean connectivity of the resulting sub-network was examined in the ADHD and control groups. Resting state functional connectivity (RSFC) analysis revealed significantly reduced connectivity under MPH compared to placebo in young people with ADHD. Findings were robust across a range of thresholds. No sub-networks of increased connectivity were found at any threshold. Mean connectivity of the identified sub-network was significantly higher in ADHD individuals in the placebo condition compared to controls, however there was no difference between MPH condition and controls. We demonstrated a significant MPH-related reduction in RSFC in a large, robust network primarily involving occipital, temporal and cerebellar regions, and visual, executive and default mode networks. These findings suggest that MPH is ‘normalising’ a higher RSFC in young people with ADHD. This study is a novel addition to the understanding of treatment effects on the brain in ADHD.

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Acknowledgments

This work was supported by a Project Grant to MAB and AV (No. 569533) from the National Health and Medical Research Council of Australia. TS was supported by a NHMRC Career Development Award. The research was conducted within the Academic Child Psychiatry Unit, University of Melbourne, Royal Children’s Hospital and the Developmental Imaging research group, Murdoch Childrens Research Institute (MCRI) and the Children’s MRI Centre, Royal Children’s Hospital, Melbourne, Victoria. It was also supported by The Royal Children’s Hospital Foundation and the Victorian Government’s Operational Infrastructure Support Program. This trial was registered at Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12610000652077. We thank Alex Fornito for his feedback on the manuscript.

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Authors and Affiliations

  1. Developmental Imaging, Murdoch Childrens Research Institute, The Royal Children’s Hospital, Melbourne, Australia

    Timothy J Silk & Charles Malpas

  2. Department of Paediatrics, The University of Melbourne, Melbourne, Australia

    Timothy J Silk

  3. Academic Child Psychiatry Unit, Department of Paediatrics, The University of Melbourne, The Royal Children’s Hospital, Melbourne, Australia

    Alasdair Vance

  4. School of Psychological Sciences, Monash University, Melbourne, Australia

    Mark A. Bellgrove

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  1. Timothy J Silk
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Correspondence to Timothy J Silk.

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This work was supported by a Project Grant to MAB and AV (No. 569,533) from the National Health and Medical Research Council of Australia.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Silk, T.J., Malpas, C., Vance, A. et al. The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD. Brain Imaging and Behavior 11, 1422–1431 (2017). https://doi.org/10.1007/s11682-016-9620-8

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