Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri; Biological Sciences Division, University of Chicago, Chicago, Illinois.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jan;4(1):50-61. doi: 10.1016/j.bpsc.2018.09.008. Epub 2018 Oct 2.
Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown.
Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory.
Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior.
These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.
在许多日后被诊断出患有自闭症谱系障碍(ASD)的婴儿中,12 个月时就能发现受限和重复行为(RRBs),这些行为可能是 ASD 的一些最早的行为标志物。然而,这些关键行为出现的大脑功能仍不清楚。
从具有 ASD 高家族风险和低家族风险的 167 名儿童(12 个月和 24 个月时各有 38 名)处收集行为和静息态功能连接磁共振成像数据。20 名婴儿在 24 个月时符合 ASD 标准。我们将 RRBs 分为四个亚类(受限、刻板、仪式性/同一性、自伤),并使用数据驱动的方法确定与每个 RRBs 亚类发展相关的功能大脑网络。
仪式性/同一性行为的评分越高,在 12 个月和 24 个月时,视觉网络和对照组网络之间的正功能连接就越低。在 12 个月时,仪式性/同一性行为和刻板行为与视觉网络和默认模式网络之间的正功能连接较低有关。在 24 个月时,刻板行为和受限行为与默认模式和对照组网络之间的正功能连接较高有关。此外,在 24 个月时,刻板行为与背侧注意和皮质下网络之间的正功能连接较高有关,而受限行为与默认模式和背侧注意网络之间的正功能连接较高有关。自伤行为没有显著的网络水平关联。
这些观察结果标志着迄今为止已知的 RRBs 背后的功能大脑系统的最早描述,增强了婴儿 RRBs 亚类的结构效度,并暗示了针对 RRBs 的未来干预的特定神经基质。