title: Pattern classification of working memory networks reveals differential effects of methylphenidate, atomoxetine, and placebo in healthy volunteers.
abstract: 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.
authors.affiliation: Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK. andre.marquand@kcl.ac.uk
authors.forename: Andre F
authors.initials: AF
authors.lastname: Marquand
authors.forename: Sara
authors.initials: S
authors.lastname: De Simoni
authors.forename: Owen G
authors.initials: OG
authors.lastname: O'Daly
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Janaina
authors.initials: J
authors.lastname: Mourão-Miranda
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008570:Memory, Short-Term / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D008774:Methylphenidate / Q000494:pharmacology*; D009483:Neuropsychological Tests / Q000592:standards; D015990:Placebo Effect; D011437:Propylamines / Q000494:pharmacology*; D012201:Reward; D013647:Task Performance and Analysis; D055815:Young Adult
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride