Department of Pediatrics, Jichi Medical University, Shimotsuke, Japan.
Applied Cognitive Neuroscience Lab, Chuo University, Tokyo, Japan.
Brain Dev. 2024 Nov;46(10):373-382. doi: 10.1016/j.braindev.2024.09.004. Epub 2024 Oct 11.
This study undertook neuropharmacological research on the clinical course of controlled medication discontinuation to guide practitioners who are considering stopping medications for youths with attention-deficit hyperactivity disorder (ADHD).
This study analyzed the data for 14 ADHD children (12 male and 2 female) in two datasets: The children prescribed methylphenidate (MPH) were at an initial mean age of 7.5 years (SD = 1.70, range: 6-11) with a mean ADHD-Rating Score (ADHD-RS) of 26.6 (SD = 8.64, range 15-40). The children who discontinued MPH based on clinical judgment were at a mean age of 12.21 years (SD = 2.12, range: 8-15) with a mean ADHD-RS of 15.9 (SD = 6.86, range 5-27). The go/no-go task was used to assess response inhibition, while functional near-infrared spectroscopy (fNIRS) was used to measure cerebral hemodynamics. Oxygenated hemoglobin (Oxy-Hb) values from fNIRS data were analyzed for each subject, focusing on past and current measurements. Baseline was set at 10 s pre-task, with interval means from 4 to 24 s analyzed. One-sample t-tests were used to evaluate brain activity magnitude.
The results of the study demonstrate that the children who had discontinued the medication exhibited activation in specific brain regions including the frontopolar cortex and the right ventrolateral prefrontal cortex. Activation (t = 2.363, p = 0.034, Cohen's d = 0.632) was found especially in the right dorsolateral prefrontal cortex during the performance of the go/no-go task. These activated areas were consistent with those observed in a previous study comparing brain activity during a go/no-go task between children with ADHD and healthy children.
The present study showed differences in cerebral hemodynamics before and after discontinuation of MPH in ADHD children whose ADHD symptoms did not recur after MPH was discontinued. In the near future, further investigations that include control groups will be conducted to demonstrate the effects of MPH prior to discontinuation based on the changes in cerebral blood flow in the right prefrontal cortex, which is involved in behavioral inhibition, as observed in this study. This and future research will facilitate the development of criteria for discontinuing treatment.
本研究对停药过程中的临床情况进行神经药理学研究，以指导考虑停止为患有注意缺陷多动障碍（ADHD）的青少年开处方药物的临床医生。
本研究分析了来自两个数据集的 14 名 ADHD 儿童（12 名男性和 2 名女性）的数据：服用哌甲酯（MPH）的儿童初始平均年龄为 7.5 岁（SD=1.70，范围：6-11），平均 ADHD-Rating 评分（ADHD-RS）为 26.6（SD=8.64，范围 15-40）。根据临床判断停用 MPH 的儿童的平均年龄为 12.21 岁（SD=2.12，范围：8-15），平均 ADHD-RS 为 15.9（SD=6.86，范围 5-27）。使用 Go/No-Go 任务评估反应抑制，同时使用功能近红外光谱（fNIRS）测量大脑血流动力学。对每个受试者的 fNIRS 数据进行氧合血红蛋白（Oxy-Hb）值分析，重点关注过去和当前的测量值。基线设置为任务前 10 秒，分析间隔均值为 4 至 24 秒。使用单样本 t 检验评估大脑活动幅度。
研究结果表明，停药的儿童在特定脑区表现出激活，包括额极皮层和右侧腹外侧前额叶皮层。在执行 Go/No-Go 任务时，特别是在右侧背外侧前额叶皮层发现了激活（t=2.363，p=0.034，Cohen's d=0.632）。这些激活区域与先前比较 ADHD 儿童和健康儿童在 Go/No-Go 任务期间大脑活动的研究中观察到的区域一致。
本研究显示，在 ADHD 儿童停止使用 MPH 后 ADHD 症状未复发的情况下，停止使用 MPH 前后大脑血液动力学存在差异。在不久的将来，将进行包括对照组在内的进一步研究，以根据本研究中观察到的右侧前额叶皮质参与行为抑制的脑血流变化，证明停止治疗前 MPH 的效果。这项和未来的研究将有助于制定停药治疗的标准。
