From the Division of Neurology (D.L.G., D.A.H., S.W.W., E.V.P., P.S.H.) and Department of Psychiatry (E.V.P.), Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, OH; Center for Neurodevelopmental and Imaging Research (K.H., D.C., S.H.M.), Kennedy Krieger Institute, Baltimore; Behavioral Neurology Unit (E.M.W.), National Institute of Neurological Disorders and Stroke, NIH, Bethesda; and Departments of Neurology and Psychiatry (S.H.M.), Johns Hopkins University School of Medicine, Baltimore, MD.
Neurology. 2019 Aug 6;93(6):e599-e610. doi: 10.1212/WNL.0000000000007899. Epub 2019 Jul 17.
Compared to typically developing (TD) peers, children with attention-deficit/hyperactivity disorder (ADHD) consistently demonstrate impaired transcranial magnetic stimulation (TMS)-evoked short interval cortical inhibition (SICI) of motor evoked potentials (MEPs) in resting motor cortex (M1). To determine whether perturbed M1 physiology also reflects clinically relevant behavioral dysfunction, we evaluated M1 physiology during a cognitive control task taxing motor response selection/inhibition.
In this case-control study, behavioral ratings, motor skill (assessed using standardized examination), and left M1 physiology were evaluated in 131 right-handed, 8- to 12-year-old children (66 ADHD: mean 10.5 years, 43 male; 65 TD: mean 10.6 years, 42 male). The primary outcomes were MEP amplitudes and SICI, evaluated during rest and during a modified "racecar" Slater-Hammel stop signal reaction task, with TMS pulses administered 150 ms prior to the target go action and after the dynamic stop cue.
Go responses were significantly slower ( = 0.01) and more variable ( = 0.002) in ADHD. Children with ADHD showed less M1 SICI at rest ( = 0.02) and during go ( = 0.03) and stop trials ( = 0.02). Rest M1 excitability increased during response inhibition task engagement ( < 0.0001). This Task-Related Up-Modulation (TRUM) was less robust across and within groups, with diminished task upmodulation associated with significantly more severe ADHD behavioral ratings and slower stop signal reaction times.
Children with ADHD show anomalous motor cortex physiology, with deficient SICI across behavioral states and less TRUM from rest to action selection. Associations of these physiologic measures with ADHD symptoms and cognitive control measures support further investigation into biological mechanisms.
与典型发育(TD)同龄人相比,患有注意缺陷/多动障碍(ADHD)的儿童在静息运动皮层(M1)中运动诱发电位(MEP)的经颅磁刺激(TMS)诱发的短程皮质抑制(SICI)始终表现出受损。为了确定受干扰的 M1 生理学是否也反映了与临床相关的行为功能障碍,我们在一项需要运动反应选择/抑制的认知控制任务中评估了 M1 生理学。
在这项病例对照研究中,我们评估了 131 名右利手 8 至 12 岁儿童(66 名 ADHD:平均年龄 10.5 岁,43 名男性;65 名 TD:平均年龄 10.6 岁,42 名男性)的行为评分、运动技能(使用标准化考试评估)和左侧 M1 生理学。主要结果是在休息时和在修改后的“赛车”Slater-Hammel 停止信号反应任务期间评估 MEP 幅度和 SICI,其中 TMS 脉冲在目标动作之前 150 毫秒和动态停止线索之后施加。
ADHD 儿童的反应明显较慢(=0.01),且变化较大(=0.002)。与静息(=0.02)和去(=0.03)和停止试验(=0.02)时相比,ADHD 儿童的 M1 SICI 减少。在反应抑制任务参与期间,静息 M1 兴奋性增加(<0.0001)。这种任务相关的上调(TRUM)在组间和组内都不太稳健,任务上调减少与 ADHD 行为评分明显更严重和停止信号反应时间更慢相关。
患有 ADHD 的儿童表现出异常的运动皮层生理学,在行为状态下 SICI 受损,从休息到动作选择的 TRUM 减少。这些生理测量与 ADHD 症状和认知控制测量的关联支持进一步研究生物机制。