PHENOCADES: Developmental neurodynamics of phenotypic cascades in autism and ADHD

自闭症和注意力缺陷多动障碍（ADHD）等神经发育状况影响多达10%的儿童，并与其他心理健康问题有关。这两种情况都与教育程度、职业成功和生活质量下降有关，因此必须进行有效的识别和干预。虽然自闭症和多动症通常直到学龄或更大的时候才被发现，但产前存在基础遗传和环境因素，并且可以从婴儿早期检测到行为和大脑变化。因此，自闭症和ADHD行为症状的因果机制在早期发展中最为清晰，在完整的症状特征出现之前。在Phenocades中，我们将测试我们的新理论，即行为症状是由影响儿童行为的感觉处理和活动调节的早期变化引起的，从而破坏了支撑社会参与和执行注意力的神经系统的经验依赖性专业化。为此，我们将招募一组新的有自闭症和/或ADHD家族史的婴儿，他们将在10个月、14个月和24个月时完成多模式方案。这是第一次，我们将使用超扫描和可穿戴神经成像来测量探索和互动过程中大脑功能的动态;收集基于家庭的数据来捕捉孩子与自然环境的互动;并使用行为可转移性实验来产生对早期行为差异如何塑造后期大脑功能的因果见解。为了检查长期结果并检查婴儿神经发育特征的遗传结构，我们将对现有的多模态纵向数据进行新的分析，这些数据来自n=600名有自闭症/ADHD家族史的婴儿，结果为3至7岁。总之，这项工作将产生对神经发育条件的发育途径的变革性新见解。

Neurodevelopmental conditions such as autism and Attention deficit hyperactivity disorder (ADHD) affect up to 10% of children and are associated with other mental health difficulties. Both conditions are associated with reduced educational attainment, occupational success and quality of life, making effective identification and intervention imperative. Although autism and ADHD are not typically recognised until school age or older, underpinning genetic and environment factors are present prenatally and behavioural and brain changes can be detected from early infancy. Thus, the causal mechanisms that underpin behavioural symptoms of autism and ADHD are clearest in early development, before the full symptom profile emerges. Within Phenocades, we will test our new theory that behavioural symptoms result from early-emerging changes in sensory processing and activity regulation that affect a child's behaviour, thus disrupting the experience-dependent specialisation of neural systems underpinning social engagement and executive attention. To do this, we will recruit a new cohort of infants with a family history of autism and/or ADHD who will complete in a multimodal protocol at 10, 14 and 24 months. For the first time, we will measure the dynamics of brain function during exploration and interaction using hyperscanning and wearable neuroimaging; collect home-based data to capture a child's interaction with their natural environment; and use behavioural shiftability experiments to yield causal insights into how early differences in behaviour shape later brain function. To examine longer-term outcomes and examine the genetic architecture of infant neurodevelopmental traits, we will conduct new analysis of existing multimodal longitudinal data from n=600 infants with a family history of autism/ADHD with outcome at 3 to 7 years. Taken together, this work will generate transformative new insights into developmental pathways to neurodevelopmental conditions.