ADHD儿童视觉空间注意缺陷的神经机制研究

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, with estimated prevalence of about 5%. ADHD severely affects patients’ study, career and life, leading to a huge burden on patients’ families and the whole society. Visual spatial attention is one of the most fundamental kinds of attention and the base of cognitive activity, which plays an important role in cognitive learning ability of human being. Previous studies reported that children with ADHD have defects in their visual spatial attention. However, the neural mechanisms are still poorly understood. Based on our previous studies measured individual behavior performances and the event-related potentials (ERP), the purpose of the current project is to explore visual spatial attention by utilizing both ERP with high temporal resolution and magnetic resonance imaging (MRI) with high spatial resolution. We recruit children with ADHD and healthy controls and collect their ERP and fMRI data during a visuo-spatial attention task. The cognitive performances, ERP , brain structure, brain function and neural connections will be investigated by the multimodal fusion analysis. It is expected to observe the abnormality of the ERP, brain structure, neural connections and network that link to visuo-spatial attention deficiencies in children with ADHD. These findings will shed more light on the understanding of neural mechanisms and identification of biological markers, supporting the precise evidence for individual-based therapeutic strategy and selecting target in patients with ADHD.

注意缺陷多动障碍（ADHD）是一种常见的儿童神经发育障碍性疾病，患病率约为5%，该病严重影响患者的学业、职业和生活，给其家庭和社会造成沉重负担。视觉空间注意与认知学习能力密切相关，临床症状及行为学研究表明ADHD儿童存在视觉空间注意缺陷，但神经机制尚不清楚。本项目拟在既往ADHD行为学及脑电事件相关电位（ERP）研究基础上，围绕视觉空间注意功能，联合使用高时间分辨率的ERP技术和高空间分辨率的磁共振影像技术，对ADHD患者和正常儿童的视觉空间注意功能进行认知功能评定、ERP、磁共振成像（结构与功能以及神经连接）检测，在此基础上进行多模态融合分析，明确与ADHD儿童视觉空间注意功能缺陷相关的脑电成分及特异脑区、脑区连接及脑网络异常的关系。本项目预期结果有助于揭示ADHD的神经病理机制、寻找与疾病相关的生物学标志，并为ADHD患者的诊断、治疗靶点的选择及个性化治疗策略提供精准的科学依据。

视觉空间注意与认知学习能力密切相关，既往临床症状及行为学研究表明ADHD儿童存在视觉空间注意缺陷，但其神经机制尚不清楚。本项目围绕视觉空间注意功能，联合使用高时间分辨率的ERP技术和高空间分辨率的磁共振影像技术，探讨ADHD儿童视觉空间注意功能缺陷相关的脑电成分及特异脑区、脑区连接及脑网络异常的关系，帮助进一步示揭示 ADHD 的神经病理机制。具体结果如下：1）脑电ERP研究发现ADHD儿童视知觉发育过程偏离正常，且其皮层功能分化以及认知网络特异性方面发育滞后，以上异常与ADHD的注意缺陷症状相关；2）ADHD儿童前额Theta波同步现象降低、Alpha波调制增强以及Theta-Alpha相关性减弱，可能参与了ADHD执行控制功能及注意网络缺陷的神经病理机制；3）服用单剂量哌甲酯后，视觉空间注意任务诱发的脑电N2pc成分和后部P3波幅变化可以有效预测药物治疗的长期效果，提示其可能是ADHD的潜在的生物标记物；4）在清醒闭眼静息条件下，ADHD儿童Alpha波网络连接效率和模块化程度降低与其脑智发育水平密相关，且不同亚型ADHD儿童其脑电微状态特征不同，显著的亚型区分特征存在于视觉网络（脑电微状态B），脑电微状态和频率特征可作为检测ADHD及其亚型的灵敏指标，为ADHD的早期准确诊断提供了新的窗口。5）脑MRI研究发现ADHD儿童视觉空间注意功能相关的顶下小叶、大脑腹侧注意网络及额叶–顶叶网络的活动水平减弱，且与ADHD的行为表现和多动冲动症状相关；6）脑电-磁共振两种模态联合分析发现ADHD儿童在视觉搜索过程的异常感知激活可能与加工新异刺激的凸显网络及负责抑制控制的皮层-纹状体环路的异常活动有关。以上结果对寻找与疾病相关的生物学标志、以及为 ADHD 患者的诊断、干预训练靶点的选择提供了精准的科学依据。