Learning and brain plasticity in children with autism: relation to cognitive inflexibility and restricted-repetitive behaviors

儿童时期的学习障碍会对学业和职业成功以及生活质量产生不利的长期影响。学习障碍对患有自闭症谱系障碍（ASD）的儿童尤其有害。与同龄人相比，自闭症儿童在中学后教育、就业和独立生活方面的水平较低。然而，自闭症儿童学习背后的认知、行为和神经机制仍然知之甚少。ASD的特点是临床表现和认知能力的异质性，可能导致患儿的学习情况高度变化。在任何认知领域，我们对ASD学龄儿童学习的神经生物学知之甚少。在目前的项目期间，我们在一大群ASD儿童中发现了数学能力的异质性模式，这与流行病学报告表明17-40%的ASD儿童的数学成绩低于预期的结果一致。我们还发现了新的证据，表明数学能力与限制性和重复性兴趣和行为（RRIB）有关，这是ASD的核心临床症状。我们建议，在这次更新中，利用我们的创新和高影响力的研究线来调查自闭症儿童学习和大脑可塑性的异质性，以及它与RRIB和认知不灵活性的联系。使用理论激励的认知训练方案，最先进的脑成像和先进的多元计算技术，我们提出验证以下假设：(i) ASD和低数学能力儿童（LMA-ASD）相对于ASD和高数学能力儿童（HMA-ASD）和正常发展儿童（TD）会表现出不同的学习特征，（ii）与HMA-ASD和TD组相比。LMA-ASD组将显示出对数学学习很重要的两个不同的大脑系统的可塑性较弱：位于顶叶内沟和梭状回的视觉空间数字系统，以及位于内侧颞叶的陈述性记忆系统。我们还将研究RRIB和认知不灵活性是否对ASD患者的学习产生负面影响，并确定这些影响在多大程度上是由显著性网络（一个锚定在前岛和前扣带皮层的前额叶认知控制系统）的异常功能介导的。这项工作将为ASD儿童异质学习的神经认知基础提供重要的新见解，并且与NIH“自闭症谱系障碍研究”（PA-16-388）的使命高度相关。以定量严谨的方式确定学习异质性的行为和神经来源及其与临床症状的联系，将对了解ASD的病因具有重要意义，更重要的是，对于优化受影响儿童的学习具有重要意义。

Learning disabilities during childhood have adverse long-term consequences for academic and professional success and quality of life. Impaired learning can be particularly detrimental for children with autism spectrum disorder (ASD). Relative to their peers, children with ASD go on to achieve lower levels of post-secondary education, employment, and independent living. Yet, the cognitive, behavioral, and neural mechanisms underlying learning in children with ASD remain poorly understood. ASD is characterized by heterogeneous clinical presentations and cognitive abilities, likely resulting in highly variable learning profiles in affected children. Little is known about the neurobiology of learning in school-age children with ASD in any cognitive domain. In the current project period, we found heterogeneous patterns of math abilities in a large cohort of children with ASD, consistent with epidemiological reports indicating that 17-40% of children with ASD display lower-than-expected math achievement scores. We also found novel evidence that math abilities are associated with restricted and repetitive interests and behaviors (RRIB), a core clinical symptom of ASD. We propose, in this renewal, to leverage our innovative and high-impact line of research to investigate heterogeneity in learning and brain plasticity, and its links to RRIB and cognitive inflexibility, in children with ASD. Using a theoretically motivated cognitive training protocol, state-of-the-art brain imaging, and advanced multivariate computational techniques, we propose to test the hypotheses that (i) children with ASD and low math abilities (LMA-ASD) will show different learning profiles relative to children with ASD and high math abilities (HMA-ASD) and typically developing (TD) children and (ii) compared to the HMA-ASD and TD groups, the LMA-ASD group will demonstrate weaker plasticity in two distinct brain systems important for math learning: the visuospatial number system, anchored in the intra-parietal sulcus and fusiform gyrus, and the declarative memory system, anchored in the medial temporal lobe. We will also investigate whether RRIB and cognitive inflexibility have a negative influence on learning in ASD, and determine the extent to which these effects are mediated by aberrant functioning of the salience network, a prefrontal cognitive control system anchored in the anterior insula and anterior cingulate cortex. The proposed work will provide important new insights into the neurocognitive basis of heterogeneous learning profiles in children with ASD and is highly relevant to the mission of the NIH “Research on Autism Spectrum Disorders” (PA-16-388). Identifying behavioral and neural sources of heterogeneity in learning and their links to clinical symptoms in a quantitatively rigorous manner will have significant implications for informing the etiology of ASD and more critically, for optimizing learning in affected children.