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Perinatal brain maturation in children at risk of developing Autism Spectrum Conditions

有患自闭症谱系疾病风险的儿童围产期大脑成熟度

基本信息

批准号：
2065133
负责人：
金额：
--
依托单位：
King's College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2065133
关键词：
Perinatal brain maturation children risk

项目摘要

Autism spectrum conditions (ASC) comprise a range of neurodevelopmental disorders, characterized by impaired social communication and interaction and restricted, stereotyped behaviours and interests. Although the aetiology remains unclear, one theory that has gained considerable traction is the disrupted connectivity theory. This theory suggests that symptoms are due to atypical synchronization of brain functional activity. Individuals with ASD may be unable to engage or disengage brain networks as effectively as typically developing individuals. Resting-state functional magnetic resonance imaging (rs-fMRI) studies offer support to the disrupted connectivity theory of ASC [1]. However, with ASC being a neurodevelopmental disorder, and parents often reporting initial concerns as early as 12-14 months, it is unclear to what extent abnormalities reflect a primary pathophysiology of the condition, and to what extent they are secondary or compensatory effects. This has motivated efforts to study the brain as early in life as possible, before it is shaped by postnatal mechanisms or the experiences of living with autistic traits. As infants with a family history of ASC (FAM+) are more vulnerable to developing ASC themselves than children without a family history (FAM-)[2], prospective study of these infants provides a mean of assessing biological mechanisms associated with vulnerability to ASC. The first study using fMRI to characterize functional connectivity in FAM+ infants demonstrated that abnormalities in functional connectivity at 6 months can predict diagnostic outcome at 24 months [3]. Subsequent studies showed that over-connectivity in occipital regions at 12 months and basal ganglia at 24 months is linked to delays in motor behaviour [4], that underconnectivity between the visual network and frontoparietal cortex and the default mode network is associated with ritualistic/sameness behaviour at 12 months, and that overconnectivity between dorsal attention network and subcortical regions, and between default mode network and the frontoparietal network is associated with stereotyped behaviours at 24 months [5]. Most recently, our group showed that FAM+ neonates also have significantly higher neural activity in regions responsible for processing higher-order social information [6]However, studies to date have used the entire time series to derive the average connectivity between regions. This operates under the assumption that the brain's functional architecture is static. There is however growing appreciation that neural communication between networks is highly flexible, and important temporal information may therefore be lost in static fMRI analysis [7]. As dynamic functional connectivity in the developing brain remains unexplored, both in typical development and in infants with an increased risk of ASC, the proposed work aims to explore dynamic functional connectivity in infants with a family history of ASC, embedded within the context of understanding typical brain development. This may provide critical new insights into the aetiology of ASC, potentially leading to the development of new biomarkers based on the brains transient network dynamics. This work will add to years of research in imaging biomarkers for abnormal neurodevelopment performed by our group, which benefits strongly from expertise in neonatal imaging, as well as the clinical aspects of neurodevelopmental disorders such as ASC. 1)To describe and relate static and dynamic functional connectivity measures in typically developing infants 2)To explore how the observed dynamic connectivity patterns relate to fluctuations in sleep state The candidate will then explore divergence from typical connectivity patterns by addressing the next set of aims, namely: 3)To explore differences in transient connectivity states between typically developing infants and infants with a family history of autism spectrum conditions

自闭症谱系障碍（ASC）包括一系列神经发育障碍，其特征是社会沟通和互动受损，行为和兴趣受到限制。虽然病因尚不清楚，但有一个理论已经获得了相当大的吸引力，那就是连接中断理论。这一理论表明，症状是由于大脑功能活动的非典型同步。患有ASD的个体可能无法像典型的发展中个体那样有效地参与或脱离大脑网络。静息态功能磁共振成像（rs-fMRI）研究为ASC的中断连接理论提供了支持[1]。然而，由于ASC是一种神经发育障碍，并且父母通常早在12-14个月时就报告了最初的担忧，因此尚不清楚异常在多大程度上反映了该病症的主要病理生理学，以及它们在多大程度上是继发性或代偿性效应。这促使人们尽可能早地研究大脑，以免它被产后机制或自闭症特征的生活经历所塑造。由于有ASC家族史的婴儿（FAM+）比没有家族史的儿童（FAM-）更容易发展ASC [2]，因此对这些婴儿的前瞻性研究提供了评估与ASC易感性相关的生物学机制的方法。第一项使用fMRI表征FAM+婴儿功能连接的研究表明，6个月时功能连接的异常可以预测24个月时的诊断结果[3]。随后的研究表明，12个月时枕叶区域和24个月时基底神经节的过度连接与运动行为的延迟有关[4]，视觉网络和额顶叶皮层以及默认模式网络之间的连接不足与12个月时的仪式/相同行为有关，并且背侧注意网络和皮层下区域之间的过度连接，默认模式网络和额顶叶网络之间的差异与24个月时的刻板行为有关[5]。最近，我们的研究小组表明，FAM+新生儿在负责处理高阶社会信息的区域中也具有显着更高的神经活动[6]然而，迄今为止的研究已经使用了整个时间序列来推导区域之间的平均连接。这是在大脑的功能结构是静态的假设下进行的。然而，人们越来越认识到网络之间的神经通信非常灵活，因此在静态fMRI分析中可能会丢失重要的时间信息[7]。由于发育中大脑的动态功能连接尚未探索，无论是在典型发育中还是在ASC风险增加的婴儿中，拟议的工作旨在探索具有ASC家族史的婴儿的动态功能连接，嵌入在理解典型大脑发育的背景下。这可能为ASC的病因学提供关键的新见解，可能导致基于大脑瞬态网络动力学的新生物标志物的开发。这项工作将增加我们小组对异常神经发育的成像生物标志物的多年研究，该研究从新生儿成像的专业知识以及神经发育障碍（如ASC）的临床方面受益匪浅。1）描述和关联典型发育中的婴儿的静态和动态功能连接测量2）探索观察到的动态连接模式如何与睡眠状态的波动相关候选人然后将通过解决下一组目标来探索与典型连接模式的分歧，即：3）探索典型发育婴儿和具有自闭症谱系疾病家族史的婴儿之间的瞬时连接状态的差异