Objective

The combination of d-methylphenidate and guanfacine (an α-2A adrenergic agonist) may be an effective alternative to either agent as monotherapy in children with attention-deficit/hyperactivity disorder (ADHD). This study investigated the neural mechanisms underlying medication effects using cortical source analysis of electroencephalography (EEG) data.

Method

A total of 172 children with ADHD (aged 7-14; 118 boys) completed an 8-week randomized, double-blind, comparative study with 3 treatment arms: d-methylphenidate, guanfacine, or their combination. EEG modulations of brain oscillations at baseline and end point were measured during a spatial working memory task from cortical sources localized within the anterior cingulate (midfrontal) and primary visual cortex (midoccipital), based on previously reported ADHD and control differences. Linear mixed models examined treatment effects on EEG and performance measures.

Results

Combined treatment decreased midoccipital EEG power across most frequency bands and task phases. Several midoccipital EEG measures also showed significantly greater changes with combined treatment than with monotherapies. D-methylphenidate significantly increased midoccipital theta during retrieval, while guanfacine produced only trend-level reductions in midoccipital alpha during maintenance and retrieval. Task accuracy improved with combined treatment, was unchanged with d-methylphenidate, and worsened with guanfacine. Treatment-related changes in midoccipital power correlated with improvement in ADHD severity.

Conclusion

These findings show that combined treatment ameliorates midoccipital neural activity associated with treatment-related behavioral improvements and previously implicated in visuo-attentional deficits in ADHD. Both monotherapies had limited effects on EEG measures, with guanfacine further showing detrimental effects on performance. The identified midoccipital EEG profile may aid future treatment monitoring for children with ADHD.

Clinical trial registration information

Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); https://clinicaltrials.gov/; NCT00429273.

Diversity & Inclusion Statement

We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group.

中文翻译：

---

哌醋甲酯、胍法辛和联合治疗对注意缺陷/多动障碍患者空间工作记忆脑电图的影响

客观的

d-哌醋甲酯和胍法辛（一种 α-2A 肾上腺素能激动剂）的组合可能是注意力缺陷/多动障碍 (ADHD) 儿童单一疗法的有效替代品。本研究使用脑电图 (EEG) 数据的皮质源分析来研究药物作用的神经机制。

方法

共有 172 名 ADHD 儿童（7-14 岁；118 名男孩）完成了一项为期 8 周的随机、双盲、比较研究，采用 3 个治疗组：d-哌醋甲酯、胍法辛或其组合。基于先前报告的 ADHD 和控制差异，在前扣带回（中额叶）和初级视觉皮层（枕中部）内的皮质来源的空间工作记忆任务期间测量基线和终点脑振荡的脑电图调制。线性混合模型检查了治疗对 EEG 和性能指标的影响。

结果

联合治疗降低了大多数频段和任务阶段的枕中脑电图功率。几种枕中脑电图测量也显示联合治疗的变化明显大于单一疗法。D-哌醋甲酯在检索过程中显着增加了枕中部 θ，而胍法辛在维持和检索期间仅产生了枕中部 alpha 的趋势水平降低。联合治疗提高了任务准确性，d-哌醋甲酯没有变化，而胍法辛则恶化了。治疗相关的枕中肌力量变化与 ADHD 严重程度的改善相关。

结论

这些发现表明，联合治疗可改善与治疗相关的行为改善相关的枕中神经活动，并且先前与 ADHD 的视觉注意力缺陷有关。两种单一疗法对脑电图测量的影响有限，胍法辛进一步显示出对性能的不利影响。确定的枕中脑电图可能有助于未来对 ADHD 儿童的治疗监测。

临床试验注册信息

注意力缺陷多动障碍儿童的单一药物与联合药物治疗（项目 1）；https://clinicaltrials.gov/；NCT00429273。

多元化和包容性声明

我们努力确保人类参与者招募中的种族、民族和/或其他类型的多样性。我们努力确保在招募人类参与者时实现性别平衡。本文的一位或多位作者自称是一个或多个历史上在科学界代表性不足的种族和/或族裔群体的成员。在引用与这项工作科学相关的参考文献的同时，我们还积极努力促进参考文献列表中的性和性别平衡。我们积极努力促进将历史上代表性不足的种族和/或族裔群体纳入我们的作者群体。我们积极致力于促进作者群体中的性和性别平衡。