University of Nottingham, Nottingham, UK.
J Child Psychol Psychiatry. 2011 Jul;52(7):761-71. doi: 10.1111/j.1469-7610.2010.02333.x. Epub 2010 Nov 12.
Deficits characteristic of attention deficit/hyperactivity disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the default mode network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation.
We obtained functional magnetic resonance images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate.
When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off-methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition.
During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.
注意力缺陷/多动障碍(ADHD)的特征性缺陷,包括注意力和抑制控制能力差,至少部分通过增加注意力参与的因素得到缓解,这表明多巴胺奖赏不足。注意力不集中与默认模式网络(DMN)的去激活减弱有关,DMN 是一个分布在大脑中的系统,在需要注意外部世界的任务中通常会被去激活。与对照组相比,ADHD 中与任务相关的 DMN 去激活被证明减弱。我们假设,平衡速度与抑制的动机激励会增加抑制控制任务中的任务参与度,从而增强 ADHD 中的 DMN 去激活。我们还假设,哌甲酯,一种间接多巴胺激动剂,会倾向于使 DMN 去激活的异常模式正常化。
我们从 18 名接受哌甲酯治疗的 ADHD 儿童(DSM-IV 合并亚型)和 18 名年龄在 9-15 岁的配对的典型发育儿童中获得了功能磁共振成像,这些儿童在执行定时 Go/No-go 任务时。我们操纵了平衡反应速度与抑制控制的动机激励,并在 ADHD 儿童服用和未服用哌甲酯的情况下对其进行了测试。
当 ADHD 儿童未服用哌甲酯且任务激励较低时,与对照组相比,事件相关的 DMN 去激活明显减弱,但在高激励条件下两组没有差异。在未服用哌甲酯的 ADHD 儿童中,DMN 去激活的激励调节具有统计学意义,并且明显大于典型发育儿童。当 ADHD 儿童服用哌甲酯时,事件相关的 DMN 去激活的动机调节被消除,并且在任何激励条件下,与他们的典型发育同龄人相比,都没有明显的去激活减弱。
在抑制控制任务中,ADHD 儿童表现出更高的动机阈值,在此阈值下,与任务相关的刺激变得足够显著,从而使 DMN 去激活。哌甲酯治疗使这种阈值正常化,使他们与典型发育儿童的任务相关的 DMN 去激活模式无法区分。