BACKGROUND & AIMS:
BACKGROUND:The catecholamine agonists methylphenidate and atomoxetine effectively treat attention-deficit/hyperactivity disorder (ADHD). Furthermore, dopamine agonists have shown to improve time estimation in ADHD, a core cognitive deficit. However, few have compared the effects of methylphenidate and atomoxetine on brain function in ADHD, and none during time estimation. Using single dose challenges, we investigated shared and drug-specific effects in ADHD adolescents on the neural substrates of time discrimination (TD).
METHODS:Twenty ADHD adolescent male subjects were compared in a randomized double-blind cross-over design after single doses of methylphenidate, atomoxetine, and placebo in functional magnetic resonance imaging during TD. Normalization effects were assessed by comparing brain activation under each drug condition with that of 20 healthy age-matched control subjects.
RESULTS:Relative to control subjects, patients under placebo showed TD deficits and reduced activation of ventrolateral prefrontal cortex (VLPFC)/insula, inferior frontal cortex, and supplementary motor area. Performance differences were normalized only by methylphenidate, relative to both atomoxetine and placebo. Both medications, however, significantly upregulated right VLPFC/insula activation within patients and normalized its underactivation in ADHD boys under placebo relative to control subjects. The supplementary motor area and inferior frontal cortex activation differences that were observed under placebo were reduced by methylphenidate and atomoxetine, respectively, but neither survived rigorous testing for normalization.
CONCLUSIONS:While only methylphenidate had a drug-specific effect of improving TD performance deficits, both drugs significantly upregulated and normalized right VLPFC underactivation in ADHD boys under placebo relative to control subjects, suggesting shared effects of stimulants and nonstimulants on a key prefrontal dysfunction during timing.
背景与目标:
背景:儿茶酚胺激动剂哌醋甲酯和阿莫西汀可有效治疗注意力不足/多动症(ADHD)。此外,多巴胺激动剂已显示可改善ADHD(一种核心的认知缺陷)中的时间估计。然而,几乎没有人比较过哌醋甲酯和托莫西汀对多动症大脑功能的影响,而在时间估计中则没有。使用单剂量挑战,我们调查了多动症青少年在时间歧视(TD)的神经基质上的共享和药物特异性作用。
方法:在TD期间功能性磁共振成像中,单剂量哌醋甲酯,阿托西汀和安慰剂后,在随机双盲交叉设计中对20名ADHD青春期男性受试者进行了比较。通过比较每种药物条件下的大脑激活与20位年龄匹配的健康对照者的大脑激活来评估归一化效果。
结果:与对照组相比,接受安慰剂治疗的患者表现出TD缺陷,并减少了腹侧前额叶皮层(VLPFC)/岛,额叶下皮层和辅助运动区的激活。相对于托莫西汀和安慰剂,仅通过哌醋甲酯将性能差异归一化。然而,相对于对照对象,两种药物均显着上调了患者体内正确的VLPFC /胰岛素岛激活,并使其在安慰剂下的ADHD男孩中的激活不足得以正常化。哌醋甲酯和阿托莫西汀分别减少了在安慰剂下观察到的辅助运动区和额叶下皮质激活差异,但均未通过严格的标准化测试。
结论:虽然只有哌醋甲酯具有改善TD性能缺陷的药物特异性作用,但相对于对照受试者,两种药物均显着上调了安慰剂组ADHD男孩的右VLPFC失活并使其正常化,这表明兴奋剂和非兴奋剂在定时时对关键的前额叶功能障碍具有共同的作用。 。