Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, California; School of Biological & Behavioural Sciences, Queen Mary University of London, United Kingdom.
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, California.
J Am Acad Child Adolesc Psychiatry. 2023 Jan;62(1):37-47. doi: 10.1016/j.jaac.2022.06.017. Epub 2022 Aug 10.
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.
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.
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.
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.
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.
哌甲酯与胍法辛（一种 α-2A 肾上腺素能激动剂）联合使用可能是一种有效的替代治疗方法，可作为儿童注意缺陷多动障碍（ADHD）的单一疗法。本研究使用皮质源分析脑电图（EEG）数据来研究药物作用的神经机制。
共有 172 名年龄在 7-14 岁的 ADHD 儿童（118 名男孩）完成了一项为期 8 周的随机、双盲、对照研究，有 3 种治疗组：哌甲酯、胍法辛或两者联合治疗。在空间工作记忆任务期间，根据先前报道的 ADHD 和对照组之间的差异，从皮质源（前扣带回（中额）和初级视觉皮层（中枕））测量脑电图（EEG）的脑振荡调制。线性混合模型检查了治疗对脑电图和绩效指标的影响。
联合治疗降低了大多数频带和任务阶段的中枕部 EEG 功率。一些中枕部 EEG 指标也显示出与联合治疗相比，与单一疗法相比，变化更大。哌甲酯在检索过程中显著增加了中枕部θ波，而胍法辛仅在维持和检索过程中产生中枕部α波的趋势水平降低。联合治疗可提高任务准确性，哌甲酯治疗无变化，胍法辛治疗则恶化。与治疗相关的中枕部功率变化与 ADHD 严重程度的改善相关。
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中枕部神经活动，并且之前与 ADHD 中的视觉注意力缺陷有关。两种单一疗法对 EEG 测量的影响有限，胍法辛进一步对表现产生不利影响。确定的中枕部 EEG 特征可能有助于未来对 ADHD 儿童的治疗监测。
注意缺陷多动障碍儿童的单一与联合药物治疗（项目 1）；https://clinicaltrials.gov/；NCT00429273。
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