Aberrant Development of Functional Connectivity among Resting State-Related Functional Networks in Medication-Naïve ADHD Children

ObjectiveThe aim of this study was to investigate the compromised developmental trajectory of the functional connectivity among resting-state-related functional networks (RSFNs) in medication-naïve children with attention-deficit/hyperactivity disorder (ADHD).Subjects and MethodsUsing both independent component analysis and dual regression, subject-specific time courses of 12 RSFNs were extracted from both 20 medication-naïve children with ADHD, and 20 age and gender-matched control children showing typical development (TDC). Both partial correlation coefficients among the 12 RSFNs and a resting-state resource allocation index (rsRAI) of the salience network (SN) were entered into multiple linear regression analysis to investigate the compromised, age-related change in medication-naïve ADHD children. Finally, correlation analyses were performed between the compromised RSFN connections showing significant group-by-age interaction and rsRAI of SN or clinical variables.ResultsMedication-naïve ADHD subjects failed to show age-related increment of functional connectivity in both rsRAI of SN and two RSFN connections, SN-Sensory/motor and posterior default mode/precuneus network (pDMN/prec) – anterior DMN. Lower SN-Sensory/motor connectivity was related with higher scores on the ADHD Rating Scale, and with poor scores on the continuous performance test. The pDMN/prec-aDMN connectivity was positively related with rsRAI of SN.ConclusionsOur results suggest that medication-naïve ADHD subjects may have delayed maturation of the two functional connections, SN-Sensory/Motor and aDMN-pDMN/prec. Interventions that enhance the functional connectivity of these two connections may merit attention as potential therapeutic or preventive options in both ADHD and TDC.研究目的：本研究旨在探究未经药物治疗的注意缺陷多动障碍（attention-deficit/hyperactivity disorder，ADHD）儿童，其静息态相关功能网络（resting-state-related functional networks，RSFNs）间功能连接的受损发育轨迹。 研究对象与方法：本研究采用独立成分分析（independent component analysis）与双回归法，从20名未经药物治疗的ADHD儿童，以及20名年龄、性别匹配的典型发育对照儿童（typical development control，TDC）中，提取得到12个RSFNs的被试特异性时间序列。将12个RSFNs间的偏相关系数，以及突显网络（salience network，SN）的静息态资源分配指数（resting-state resource allocation index，rsRAI）纳入多元线性回归分析，以探究未经药物治疗ADHD儿童中受损的年龄相关功能连接变化。最后，对存在显著分组×年龄交互作用的受损RSFN连接，与SN的rsRAI或临床变量开展相关分析。 研究结果：未经药物治疗的ADHD儿童，其SN的rsRAI以及两项RSFN连接（SN-感觉/运动网络连接与后默认模式/楔前叶网络（posterior default mode/precuneus network，pDMN/prec）-前默认模式网络（anterior DMN，aDMN）连接）均未出现随年龄增长的功能连接增强现象。较低的SN-感觉/运动网络连接水平与ADHD评定量表高分及持续操作测验成绩不佳呈显著相关。pDMN/prec-aDMN连接与SN的rsRAI呈正相关关系。 研究结论：本研究结果表明，未经药物治疗的ADHD儿童的两项功能连接（SN-感觉/运动网络连接与aDMN-pDMN/prec连接）可能存在成熟延迟。增强这两项功能连接的干预手段，有望成为ADHD与典型发育儿童潜在的治疗或预防方案，值得进一步关注。