Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Oct;240(10):2045-2060.
doi: 10.1007/s00213-023-06422-7. Epub 2023 Jul 27.

Single-dose effects of methylphenidate and atomoxetine on functional connectivity during an n-back task in boys with ADHD

Olivia S Kowalczyk  1 , Ana I Cubillo  2   3 , Marion Criaud  2 , Vincent Giampietro  4 , Owen G O'Daly  4 , Mitul A Mehta  4 , Katya Rubia  2
Affiliations
Randomized Controlled Trial

Single-dose effects of methylphenidate and atomoxetine on functional connectivity during an n-back task in boys with ADHD

Olivia S Kowalczyk et al. Psychopharmacology (Berl). 2023 Oct.

Abstract

Rationale: Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the effects of atomoxetine or compared the two drugs.

Objectives: This study aimed to test methylphenidate and atomoxetine effects on functional connectivity during working memory in boys with ADHD.

Methods: We tested comparative effects of methylphenidate and atomoxetine on functional connectivity during the n-back task in 19 medication-naïve boys with ADHD (10-15 years old) relative to placebo and assessed potential normalisation effects of brain dysfunctions under placebo relative to 20 age-matched neurotypical boys. Patients were scanned in a randomised, double-blind, cross-over design under single doses of methylphenidate, atomoxetine, and placebo. Controls were scanned once, unmedicated.

Results: Patients under placebo showed abnormally increased connectivity between right superior parietal gyrus (rSPG) and left central operculum/insula. This hyperconnectivity was not observed when patients were under methylphenidate or atomoxetine. Furthermore, under methylphenidate, patients showed increased connectivity relative to controls between right middle frontal gyrus (rMFG) and cingulo-temporo-parietal and striato-thalamic regions, and between rSPG and cingulo-parietal areas. Interrogating these networks within patients revealed increased connectivity between both rMFG and rSPG and right supramarginal gyrus under methylphenidate relative to placebo. Nonetheless, no differences across drug conditions were observed within patients at whole brain level. No drug effects on performance were observed.

Conclusions: This study shows shared modulating effects of methylphenidate and atomoxetine on parieto-insular connectivity but exclusive effects of methylphenidate on connectivity increases in fronto-temporo-parietal and fronto-striato-thalamic networks in ADHD.

Keywords: ADHD; Atomoxetine; Attention-deficit/hyperactivity disorder; Functional connectivity; Functional magnetic resonance imaging; Methylphenidate; Psychophysiological interaction; Working memory; fMRI.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A schematic representation of the n-back block design task. A. A visual representation of the task block structure. B. Examples of n-back conditions of different working memory load (0-, 1-, 2-, and 3-back). ITI, inter-trial interval
Fig. 2
Fig. 2
Functional connectivity during 2-back > 0-back and graphs showing mean beta values within each statistically significant cluster during 0-back and 2-back in neurotypical controls and participants with ADHD. A. Regions showing significantly higher functional connectivity with the rSPG in participants with ADHD under placebo compared to neurotypical controls. B. Regions of greater functional connectivity with rSPG (red) and rMFG (yellow) in the ADHD group under methylphenidate compared to controls. Axial slices are marked with the z coordinate. rMFG, right middle frontal gyrus; MPH, methylphenidate; rSPG, right superior parietal gyrus
See this image and copyright information in PMC

References

    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 5. Arlington: American Psychiatric Association; 2013.
    1. Andre J, Picchioni M, Zhang R, Toulopoulou T. Working memory circuit as a function of increasing age in healthy adolescence: a systematic review and meta-analyses. NeuroImage Clin. 2015;12:940–948. doi: 10.1016/j.nicl.2015.12.002. - DOI - PMC - PubMed
    1. Ashburner J. A fast diffeomorphic image registration algorithm. NeuroImage. 2007;38:95–113. doi: 10.1016/j.neuroimage.2007.07.007. - DOI - PubMed
    1. Becker A, Steinhausen H-C, Baldursson G, et al. Psychopathological screening of children with ADHD: strengths and difficulties questionnaire in a pan-European study. Eur Child Adolesc Psychiatry. 2006;15:i56–i62. doi: 10.1007/s00787-006-1008-7. - DOI - PubMed
    1. Bédard A-CV, Newcorn JH, Clerkin SM, et al. Reduced prefrontal efficiency for visuospatial working memory in attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2014;53:1020–1030.e6. doi: 10.1016/j.jaac.2014.05.011. - DOI - PubMed

Publication types

MeSH terms

Substances