Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Psychopharmacology (Berl). 2023 Oct;240(10):2045-2060. doi: 10.1007/s00213-023-06422-7. Epub 2023 Jul 27.
Working memory deficits and associated neurofunctional abnormalities are frequently reported in attention-deficit/hyperactivity disorder (ADHD). Methylphenidate and atomoxetine improve working memory performance and increase activation of regions under-functioning in ADHD. Additionally, methylphenidate has been observed to modulate functional networks involved in working memory. No research, however, has examined the effects of atomoxetine or compared the two drugs.
This study aimed to test methylphenidate and atomoxetine effects on functional connectivity during working memory in boys with ADHD.
We tested comparative effects of methylphenidate and atomoxetine on functional connectivity during the n-back task in 19 medication-naïve boys with ADHD (10-15 years old) relative to placebo and assessed potential normalisation effects of brain dysfunctions under placebo relative to 20 age-matched neurotypical boys. Patients were scanned in a randomised, double-blind, cross-over design under single doses of methylphenidate, atomoxetine, and placebo. Controls were scanned once, unmedicated.
Patients under placebo showed abnormally increased connectivity between right superior parietal gyrus (rSPG) and left central operculum/insula. This hyperconnectivity was not observed when patients were under methylphenidate or atomoxetine. Furthermore, under methylphenidate, patients showed increased connectivity relative to controls between right middle frontal gyrus (rMFG) and cingulo-temporo-parietal and striato-thalamic regions, and between rSPG and cingulo-parietal areas. Interrogating these networks within patients revealed increased connectivity between both rMFG and rSPG and right supramarginal gyrus under methylphenidate relative to placebo. Nonetheless, no differences across drug conditions were observed within patients at whole brain level. No drug effects on performance were observed.
This study shows shared modulating effects of methylphenidate and atomoxetine on parieto-insular connectivity but exclusive effects of methylphenidate on connectivity increases in fronto-temporo-parietal and fronto-striato-thalamic networks in ADHD.
工作记忆缺陷及相关神经功能异常在注意缺陷多动障碍（ADHD）中经常被报道。哌甲酯和托莫西汀可改善工作记忆表现，并增加 ADHD 下功能障碍区域的激活。此外，已有研究观察到哌甲酯可调节与工作记忆相关的功能网络。但是，尚无研究比较托莫西汀或比较两种药物。
本研究旨在测试哌甲酯和托莫西汀对 ADHD 男孩工作记忆过程中功能连接的影响。
我们测试了哌甲酯和托莫西汀在 n-back 任务中对 19 名未经药物治疗的 ADHD 男孩（10-15 岁）的功能连接的影响，与安慰剂相比，并评估了在安慰剂下大脑功能障碍的潜在正常化效应相对于 20 名年龄匹配的神经典型男孩。患者在随机、双盲、交叉设计下接受单剂量哌甲酯、托莫西汀和安慰剂治疗，并进行扫描。对照者一次接受扫描，不接受药物治疗。
在接受安慰剂的患者中，右顶上小叶（rSPG）和左中央脑回/岛叶之间存在异常增加的连接。当患者服用哌甲酯或托莫西汀时，这种连接增加并未出现。此外，在服用哌甲酯时，与对照组相比，患者 rMFG 与扣带回-颞顶叶和纹状体-丘脑区域以及 rSPG 与扣带回-顶叶区域之间的连接增加。在患者中对这些网络进行检查显示，与安慰剂相比，哌甲酯增加了 rMFG 和 rSPG 之间以及 rSPG 与右缘上回之间的连接。然而，在患者中，在全脑水平上，在不同药物条件下均未观察到差异。未观察到药物对表现的影响。
本研究表明，哌甲酯和托莫西汀对顶叶-岛叶连接具有共同的调节作用，但哌甲酯对 ADHD 中额-颞-顶叶和额-纹状体-丘脑网络的连接增加具有独特的作用。
