Department of Child Psychiatry, Institute of Psychiatry, King's College London, London, UK.
Neuropsychopharmacology. 2011 Jul;36(8):1575-86. doi: 10.1038/npp.2011.30. Epub 2011 Mar 30.
Youth with attention deficit hyperactivity disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist methylphenidate (MPH). Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys. Medication-naïve boys with ADHD were scanned twice, in a randomized, double-blind design, under either a single clinical dose of MPH or placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys. During incongruent trials compared with congruent-oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/supplementary motor area, and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison, furthermore, showed that these normalization effects were significant. MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation.
患有注意缺陷多动障碍 (ADHD) 的年轻人在干扰抑制方面存在缺陷，这种缺陷可以通过间接儿茶酚胺激动剂哌甲酯 (MPH) 得到改善。本研究使用功能磁共振成像技术来研究单剂量 MPH 对未经药物治疗的 ADHD 男孩在干扰抑制过程中大脑激活的影响。未经药物治疗的 ADHD 男孩以随机、双盲的方式接受单次 MPH 或安慰剂治疗，同时进行西蒙任务，该任务测量干扰抑制并控制低频出现不一致试验的奇数效应。在两种药物条件下，对患者的大脑激活进行了比较。为了测试 MPH 是否具有潜在的正常化作用，将 ADHD 患者在两种药物条件下的大脑激活与健康年龄匹配的对照组男孩的大脑激活进行了比较。与一致-奇数试验相比，在不一致试验中，安慰剂条件下的 ADHD 男孩与对照组相比，大脑在干扰抑制的典型区域的激活减少，包括右额下回、左纹状体和丘脑、中扣带回/辅助运动区和左颞上回。与安慰剂相比，MPH 增加了右额下回和前运动皮层的大脑激活。在 MPH 条件下，与对照组相比，患者在右额下回和纹状体-丘脑区域不再表现出激活减少。此外，通过效应量比较，发现这些正常化效应具有显著意义。与对照组相比，MPH 显著改善了 ADHD 患者在干扰抑制期间的额纹状体功能低下，但对额内侧和颞叶功能没有影响。因此，MPH 似乎对额纹状体的激活具有特定的区域调节作用。
