Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, London, UK.
Neuropsychopharmacology. 2011 May;36(6):1237-47. doi: 10.1038/npp.2011.9. Epub 2011 Feb 23.
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.
兴奋剂和非兴奋剂药物均可减轻注意力缺陷多动障碍（ADHD）的症状。兴奋剂药物哌醋甲酯（MPH）和非兴奋剂药物阿托西汀（ATX）均广泛用于 ADHD 的治疗，但它们对人类大脑功能的影响尚不清楚。我们将事件相关 fMRI 与多元模式识别相结合，以描述 MPH 和 ATX 在执行奖励性工作记忆（WM）任务的健康志愿者中的作用。MPH 和 ATX 对 WM 的影响强烈依赖于其行为背景。在非奖励试验中，只有 MPH 可以与安慰剂（PLC）区分开，而 MPH 产生的激活模式与奖励相似。在奖励试验中，两种药物的作用均与奖励相反，即减弱 WM 网络并增强与默认模式网络（DMN）一致的区域中的任务相关去激活（TRD）。在奖励试验的延迟成分中，可以直接区分药物：MPH 可使 WM 网络的活性增加，而 ATX 可使 DMN 的活性增加。我们的数据提供了以下证据：（1）MPH 和 ATX 在任务激活和去激活网络中对奖励 WM 有明显影响；（2）在奖励试验的延迟成分中，MPH 和 ATX 对激活和去激活网络有相反的影响：MPH 增强 TRD 的作用强于 ATX，而 ATX 减弱 WM 网络的作用强于 MPH；（3）MPH 在编码过程中模仿奖励。因此，药物作用与动机状态之间的相互作用对于定义 MPH 和 ATX 的作用至关重要。
