Atypical Brain Asymmetry in Autism-A Candidate for Clinically Meaningful Stratification
Atypical Brain Asymmetry in Autism-A Candidate for Clinically Meaningful Stratification
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DOI：
10.1016/j.bpsc.2020.08.008
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发表时间：
2021-08-05
影响因子：
5.9
通讯作者：
Beckmann, Christian F.
中科院分区：
文献类型：
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作者：
Floris, Dorothea L.;Wolfers, Thomas;Beckmann, Christian F.
背景：自闭症谱系障碍(“自闭症”)是一种高度异质性的神经发育疾病，缺乏对核心和相关特征的有效治疗。为了取得进展，我们需要识别和验证有助于解析异质性的神经标记物，以根据特定的神经生物学特征定制治疗方法。在自闭症的研究中，非典型的半球偏侧化是一个稳定的特征，但它作为神经分层标记的潜力还没有被广泛研究。方法：为了分析自闭症偏侧化的异质性，我们使用了大型EU-AIMS(欧洲自闭症干预-开发新药的多中心研究)纵向欧洲自闭症项目数据集，包括352名自闭症患者和233名神经典型对照受试者，以及来自ABISE(自闭症脑成像数据交换)(513名自闭症患者，691名神经典型受试者)的复制数据集，采用了一种超越平均组比较的有前景的方法。我们得出了每个受试者的灰质体素偏侧性值，并使用标准模型模拟了不同年龄的大脑偏侧的标准模式的个体偏差。结果：自闭症患者具有高度个性化的极端右倾和左倾偏向模式，特别是在语言、运动和视觉空间区域，与症状严重程度相关。语言延迟解释了极右倾模式的大部分差异，而核心自闭症症状严重程度解释了极左倾模式的大部分差异。跟踪分析显示，出现了一种循序渐进的模式，有语言延迟的自闭症患者比没有语言延迟的自闭症患者表现出更明显的向右偏差。结论：我们的分析证实了需要新的(维度)方法来描述自闭症的异质性神经解剖结构，并表明非典型的偏侧化可能构成自闭症临床意义分层的神经表型。
BACKGROUND: Autism spectrum disorder ("autism") is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. METHODS: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions-A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. RESULTS: Individuals with autism had highly individualized patterns of both extreme right-and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. CONCLUSIONS: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.