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对学业和职业成功以及生活质量具有长期的不利影响。学习障碍对自闭症谱系障碍（ASD）儿童尤其有害。与同龄人相比，ASD儿童继续获得较低水平的中学后教育，就业和独立生活。然而，ASD儿童学习的认知，行为和神经机制仍然知之甚少。ASD的特点是异质性的临床表现和认知能力，可能导致受影响儿童的学习特征高度可变。对于ASD学龄儿童在任何认知领域的学习神经生物学知之甚少。在当前的项目期间，我们在一个大型ASD儿童队列中发现了数学能力的异质模式，这与流行病学报告一致，该报告表明17-40%的ASD儿童显示出低于预期的数学成绩。我们还发现了新的证据，表明数学能力与受限和重复的兴趣和行为（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，调查学习和大脑可塑性的异质性，及其与RRIB和认知能力的联系，在ASD儿童中。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变量计算技术，我们建议测试以下假设：（i）ASD和低数学能力（LMA-ASD）的儿童相对于ASD和高数学能力（HMA-ASD）的儿童和典型发育（TD）儿童将显示不同的学习概况，（ii）与HMA-ASD和TD组相比，LMA-ASD组将在两个对数学学习很重要的不同脑系统中表现出较弱的可塑性：固定在顶内沟和梭状回中的视觉空间数字系统，以及固定在内侧颞叶中的陈述性记忆系统。我们还将调查RRIB和认知能力是否对ASD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的异常功能介导的，显著性网络是一种前额叶认知控制系统，锚定在前额叶皮层和前扣带皮层。拟议的工作将提供重要的新见解的神经认知基础的异质性学习档案在自闭症儿童和高度相关的使命的NIH“研究自闭症谱系障碍”（PA-16-388）。识别学习异质性的行为和神经来源及其与临床症状的联系，以严格的定量方式将对ASD的病因学有重要意义，更重要的是，优化受影响儿童的学习。

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.