Exploring the links between brain function and parent-infant interaction: A longitudinal study

自闭症是一种神经发育疾病，其特征是社交互动受损，沟通受损，限制性和重复性行为和兴趣受损，在英国学校人口中患病率约为1%。由于自闭症的高遗传性，与没有自闭症的婴儿兄弟姐妹相比，患有自闭症的儿童的兄弟姐妹患自闭症或自闭症特征的风险为50%。对患有自闭症的哥哥姐姐的婴儿进行的前瞻性纵向研究表明，在两到三岁之前，行为诊断很少能被观察到，而大脑功能的测量能够在生命的第一年识别出早期的细微差异。例如，有研究表明，后来接受诊断的婴儿兄弟姐妹对眼睛注视和面孔的事件相关电位（ERP）反应发生了改变，大脑对与社会相关的视觉和听觉刺激的激活程度也有所下降。到了第二年，明显的行为迹象包括社交和交流行为的逐渐减少，比如减少共同关注、共同微笑和发声。然而，早期大脑功能的变化是否与随后的社会行为的非典型性有关尚不清楚，这可能对早期干预有重要意义。发展的交易模型支持这样一种观点，即早期婴儿社会能力的微妙中断可能会改变父母对婴儿的反应以及随后父母-婴儿社会互动中的相互关系。早期脑功能差异可能会因不同脑区和儿童社会环境相互作用的非典型而加剧，从而产生一种逐渐偏离健康表型的社会认知发展模式。例如，不典型的早期社会沟通技能可能会影响父母的反应，这可能会在无意中减少预先存在遗传脆弱性的婴儿的社会关注，导致越来越不典型的发展路线。为了支持这一观点，研究已经确定了在7个月大时，相对于低风险的自闭症婴儿，高危婴儿对眼睛凝视的大脑反应（ERPs）和亲子互动（PCI）质量之间的明确关系。研究人员在一项涉及8个月大的高危婴儿的类似研究中也发现了这两种措施之间的联系，该研究区分了后来确诊的婴儿和未确诊的婴儿，并为未来的研究提供了有希望的结果。目前的项目试图扩展这一研究，建议遵循纵向设计，以检查不同的大脑功能对社会刺激的反应是否与发育时期自闭症高风险和低风险婴儿的非结构化PCI相关，以及这种关联如何与自闭症结果相关联。特别是，PCI测量将侧重于父母的指令性，敏感反应，婴儿对父母的关注，婴儿的影响和相互关系变量。这些变量区分了高危人群和低危人群，后三个变量预测了那些后来被诊断为自闭症的人。此外，研究还发现，对眼睛凝视的ERP反应与婴儿情绪和注意力之间存在联系。综上所述，该项目将对可能导致自闭症结果的风险因素以及PCI在这些儿童的发展轨迹中可能发挥的作用提供重要的见解，这可能为确定易感婴儿支持性早期干预的新目标奠定基础。它还将为更好地理解大脑功能的测量如何与婴儿和父母之间的自然互动联系起来，以及它们是否能在评估儿童早期临床诊断风险方面发挥预测作用，提供一个垫脚石。

Autism is a neurodevelopmental condition characterised by impaired social interaction, impaired communication and restrictive and repetitive behaviours and interests with prevalence around 1% in the UK school population. Due to its high heritability, siblings of children with autism have 50% risk of developing the disorder or autistic traits compared to infant siblings without autism. Prospective longitudinal studies of infants with an older sibling with autism have shown that a behavioural diagnosis is rarely observable before the age of two to three years, while brain function measures have been able to identify early subtle differences within the first year of life. For instance, it has been shown that infant siblings who later receive a diagnosis exhibit altered event-related potential (ERP) responses to eye gaze and faces as well as a decreased brain activation to socially relevant visual and auditory stimuli. By the second year, overt behavioural signs include a gradual decrease in social and communicative behaviours, such as reduced joint attention, shared smiles and vocalisations. However, whether early brain function changes are linked to subsequent atypicalities in social behaviours is not yet clear and may have important implications for early intervention. Transactional models of development support the idea that early subtle disruptions in infants' social competence may alter parental responses towards the infant and subsequent mutuality in parent-infant social interactions. Early brain function differences may be exacerbated by atypicalities in interactions within different brain regions and the child's social environment, thereby producing a pattern of socio-cognitive development that gradually deviates from a healthy phenotype. For instance, atypical early social communicative skills are likely to influence parental responses which may inadvertently decrease social attention in infants with pre-existing genetic vulnerability, leading to an increasingly atypical developmental route. In support of this idea, research has identified clear relationships between brain responses to eye gaze (ERPs) and quality of parent-child interaction (PCI) in at-risk infants relative to those at low risk of autism at 7 months of age. Links between these two measures have also been found in a similar study undertaken by the researcher involving 8-month old infants at-risk, distinguishing later diagnosed from non-diagnosed infants, and yielding promising results for future investigation. The current project seeks to extend on this research, proposing to follow a longitudinal design in order to examine whether different measures of brain function in response to social stimuli are related to unstructured PCI in infants at high and low risk of autism over developmental time, and how this association is linked to autism outcome. Particularly, the PCI measure will focus on parental directiveness, sensitive responsiveness, infant attentiveness to parent, infant affect and mutuality variables. These variables have distinguished at-risk from low-risk groups, with the latter three variables predicting those who were later diagnosed with autism. Additionally, research has found links between ERP responses to eye gaze and infant affect and attentiveness in infants at-risk. Taken together, this project will offer significant insights into the possible risk factors leading to autism outcome and the role that PCI could play in these children's developmental trajectories, which could form the basis for identifying new targets for supportive early interventions for vulnerable infants. It will also provide a stepping stone towards a better understanding of how measures of brain function relate to naturalistic interactions between infants and their parents and whether they could both play a predictive role in assessing the risk of clinical diagnosis in early childhood.