Arnett Anne B, Rutter Tara M, Stein Mark A
Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, United States.
Department of Pediatrics, Harvard Medical School, Cambridge, MA, United States.
Front Behav Neurosci. 2022 May 6;16:887622. doi: 10.3389/fnbeh.2022.887622. eCollection 2022.
Despite widespread use of stimulants to treat ADHD, individual responses vary considerably and few predictors of response have been identified. The identification of reliable and clinically feasible biomarkers would facilitate a precision medicine approach to pharmacological treatment of ADHD. We test the hypothesis that two electroencephalography (EEG) based neural signatures of ADHD, resting aperiodic slope exponent and novelty P3 amplitude, are markers of methylphenidate response in children. We hypothesize that positive response to methylphenidate treatment will be associated with greater abnormality of both neural markers.
Twenty-nine 7-11 year-old children with ADHD and a history of methylphenidate treatment, and 30 controls completed resting EEG and visual oddball event related potential (ERP) paradigms. ADHD participants were characterized as methylphenidate responders ( = 16) or non-responders ( = 13) using the clinical global improvement (CGI-I) scale during blinded retrospective interview. All participants abstained from prescribed medications for at least 48 hours prior to the EEG.
As expected, methylphenidate responders (CGI-I rating < 3) demonstrated attenuated P3 amplitude relative to controls. Unexpectedly, methylphenidate non-responders showed atypically flat aperiodic spectral slope relative to controls, while responders did not differ on this measure.
ADHD symptoms associated with atypical patterns of intrinsic neural activity may be less responsive to methylphenidate. In contrast, ADHD symptoms associated with abnormal frontal-striatal neural network excitation may be correctable with methylphenidate. Altogether, EEG is a feasible and promising candidate methodology for identifying biomarkers of stimulant response.
尽管兴奋剂广泛用于治疗注意力缺陷多动障碍（ADHD），但个体反应差异很大，且几乎没有发现反应的预测因素。识别可靠且临床可行的生物标志物将有助于采用精准医学方法治疗ADHD。我们检验了以下假设：基于脑电图（EEG）的ADHD的两种神经特征，静息非周期性斜率指数和新奇性P3波幅，是儿童哌甲酯反应的标志物。我们假设对哌甲酯治疗的阳性反应将与这两种神经标志物的更大异常相关。
29名7至11岁患有ADHD且有哌甲酯治疗史的儿童以及30名对照组完成了静息EEG和视觉Oddball事件相关电位（ERP）范式。在盲法回顾性访谈期间，使用临床总体改善（CGI-I）量表将ADHD参与者分为哌甲酯反应者（n = 16）或无反应者（n = 13）。所有参与者在EEG检查前至少48小时停用处方药。
正如预期的那样，与对照组相比，哌甲酯反应者（CGI-I评分<3）的P3波幅减弱。出乎意料的是，与对照组相比，哌甲酯无反应者的非周期性频谱斜率异常平坦，而反应者在这一指标上没有差异。
与内在神经活动非典型模式相关的ADHD症状可能对哌甲酯反应较差。相比之下，与额纹状体神经网络异常兴奋相关的ADHD症状可能可用哌甲酯纠正。总之，EEG是识别兴奋剂反应生物标志物的一种可行且有前景的候选方法。
