Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Neuropsychopharmacology. 2011 Apr;36(5):1060-72. doi: 10.1038/npp.2010.243. Epub 2011 Jan 19.
This study examined the effects of methylphenidate (MPH) on reaction time (RT) variability in children with attention deficit hyperactivity disorder (ADHD). Using a broad battery of computerized tasks, and both conventional and ex-Gaussian indicators of RT variability, in addition to within-task manipulations of incentive and event rate (ER), this study comprehensively examined the breadth, specificity, and possible moderators of effects of MPH on RT variability. A total of 93 children with ADHD completed a 4-week within-subject, randomized, double-blind, placebo-controlled crossover trial of MPH to identify an optimal dosage. Children were then randomly assigned to receive either their optimal MPH dose or placebo after which they completed five neuropsychological tasks, each allowing trial-by-trial assessment of RTs. Stimulant effects on RT variability were observed on both measures of the total RT distribution (ie, coefficient of variation) as well as on an ex-Gaussian measure examining the exponential portion of the RT distribution (ie, τ). There was minimal, if any, effect of MPH on performance accuracy or RT speed. Within-task incentive and ER manipulations did not appreciably affect stimulant effects across the tasks. The pattern of significant and pervasive effects of MPH on RT variability, and few effects of MPH on accuracy and RT speed suggest that MPH primarily affects RT variability. Given the magnitude and breadth of effects of MPH on RT variability as well as the apparent specificity of these effects of MPH on RT variability indicators, future research should focus on neurophysiological correlates of effects of MPH on RT variability in an effort to better define MPH pharmacodynamics.
本研究考察了哌醋甲酯（MPH）对注意缺陷多动障碍（ADHD）儿童反应时（RT）变异性的影响。使用广泛的计算机化任务以及 RT 变异性的常规和外高斯指标，以及任务内激励和事件率（ER）的操作，本研究全面考察了 MPH 对 RT 变异性的影响的广度、特异性和可能的调节剂。共有 93 名 ADHD 儿童完成了一项为期 4 周的、随机、双盲、安慰剂对照的 MPH 交叉试验，以确定最佳剂量。然后，儿童被随机分配接受最佳 MPH 剂量或安慰剂，之后他们完成了五个神经心理学任务，每个任务都允许对 RT 进行逐次评估。在总 RT 分布的两个测量值（即变异系数）以及检查 RT 分布指数部分（即 τ）的外高斯测量值上都观察到了 RT 变异性的兴奋剂作用。MPH 对 RT 速度或准确性几乎没有影响。任务内激励和 ER 操作并没有明显影响任务之间的兴奋剂作用。MPH 对 RT 变异性的显著和普遍影响以及对准确性和 RT 速度的影响很小，这表明 MPH 主要影响 RT 变异性。鉴于 MPH 对 RT 变异性的影响程度和广度，以及 MPH 对 RT 变异性指标的这些影响的明显特异性，未来的研究应集中于 MPH 对 RT 变异性的神经生理相关性，以更好地定义 MPH 药效动力学。
