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Publication Detail
Pattern classification of working memory networks reveals differential effects of methylphenidate, atomoxetine, and placebo in healthy volunteers.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Clinical Trial
  • Authors:
    Marquand AF, De Simoni S, O'Daly OG, Williams SCR, MourĂ£o-Miranda J, Mehta MA
  • Publication date:
  • Pagination:
    1237, 1247
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  • Volume:
  • Issue:
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  • Keywords:
    Adrenergic Uptake Inhibitors, Adult, Atomoxetine Hydrochloride, Central Nervous System Stimulants, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Methylphenidate, Neuropsychological Tests, Placebo Effect, Propylamines, Reward, Task Performance and Analysis, Young Adult
Stimulant and non-stimulant drugs can reduce symptoms of attention deficit/hyperactivity disorder (ADHD). The stimulant drug methylphenidate (MPH) and the non-stimulant drug atomoxetine (ATX) are both widely used for ADHD treatment, but their differential effects on human brain function remain unclear. We combined event-related fMRI with multivariate pattern recognition to characterize the effects of MPH and ATX in healthy volunteers performing a rewarded working memory (WM) task. The effects of MPH and ATX on WM were strongly dependent on their behavioral context. During non-rewarded trials, only MPH could be discriminated from placebo (PLC), with MPH producing a similar activation pattern to reward. During rewarded trials both drugs produced the opposite effect to reward, that is, attenuating WM networks and enhancing task-related deactivations (TRDs) in regions consistent with the default mode network (DMN). The drugs could be directly discriminated during the delay component of rewarded trials: MPH produced greater activity in WM networks and ATX produced greater activity in the DMN. Our data provide evidence that: (1) MPH and ATX have prominent effects during rewarded WM in task-activated and -deactivated networks; (2) during the delay component of rewarded trials, MPH and ATX have opposing effects on activated and deactivated networks: MPH enhances TRDs more than ATX, whereas ATX attenuates WM networks more than MPH; and (3) MPH mimics reward during encoding. Thus, interactions between drug effects and motivational state are crucial in defining the effects of MPH and ATX.
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