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Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers

Marquand, AF; De Simoni, S; O'Daly, OG; Williams, SCR; Mourao-Miranda, J; Mehta, MA; (2011) Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers. NEUROPSYCHOPHARMACOL , 36 (6) 1237 - 1247. 10.1038/npp.2011.9.

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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. Neuropsychopharmacology (2011) 36, 1237-1247; doi: 10.1038/npp.2011.9; published online 23 February 2011

Type:Article
Title:Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers
DOI:10.1038/npp.2011.9
Keywords:methylphenidate, atomoxetine, working memory, reward, pattern recognition, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, SUPPORT VECTOR MACHINES, DEFICIT HYPERACTIVITY DISORDER, DELAYED-RESPONSE TASKS, PREFRONTAL CORTEX, HUMAN BRAIN, SUBJECTIVE FEELINGS, EXECUTIVE FUNCTION, DOPAMINE NEURONS, PERIOD ACTIVITY
UCL classification:UCL > School of BEAMS > Faculty of Engineering Science > Computer Science

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