Radiology, University of Calgary, Calgary, AB, Canada; Child and Adolescent Imaging Research Program, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Clin Neurophysiol. 2021 May;132(5):1163-1172. doi: 10.1016/j.clinph.2021.01.023. Epub 2021 Mar 10.
Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).
Across two sites, 37 children with ADHD and 45 TD children, ages 8-12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models.
In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.
In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.
Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.
与典型发育（TD）同龄人相比，患有注意缺陷多动障碍（ADHD）的儿童在经颅磁刺激（TMS）测量的优势运动皮质中表现出较短的皮质抑制（SICI）减少。这项多模态研究通过评估 SICI 与γ-氨基丁酸（GABA+）水平之间的关系，来研究抑制神经生理学和神经化学，GABA+水平是通过磁共振波谱（MRS）测量的。
在两个地点，共有 37 名 ADHD 儿童和 45 名 TD 儿童（年龄 8-12 岁）参与了研究。在改良的 Slater-Hammel 停止信号反应任务中，通过左运动皮质的单脉冲和双脉冲 TMS 在休息时和动作选择时（GO）以及抑制时（STOP）量化 SICI。MRS 定量左感觉运动皮质中的 GABA+水平。使用相关性和重复测量混合模型分析 SICI 与 GABA+之间的关系，以及停止效率与临床症状之间的关系。
在两组中，较高的 GABA+水平与较低的 SICI 相关。仅在 TD 儿童中，较高的 GABA+水平与 REST 时更高的 TMS 运动诱发电位（MEP）相关。在 GO 和 STOP 试验中，较高的 GABA+与两组的 MEP 振幅较小相关。总体而言，两组之间的 GABA+水平没有差异，也与 ADHD 临床症状无关。
在具有较高运动皮质 GABA+的儿童中，运动皮质对抑制性 TMS（SICI）的反应性较低。比较 MRS-GABA+水平与 REST 与 GO/STOP 试验中 TMS 反应之间的关系表明，ADHD 儿童的抑制神经生理学和神经递质存在差异。这些差异在休息时比在反应抑制任务参与时更为明显。
评估 GABA+和 SICI 之间的关系可能提供一种有用的生物标志物，有助于理解行为诊断。
