Brain and Behavioral Development in Autism Spectrum Disorder

青春期是一个复杂的时期，自我意识增强，冒险和同伴取向，这可能是 对于被诊断为自闭症谱系障碍（ASD）的青少年来说，这尤其具有挑战性。纵向磁 对ASD儿童的核磁共振成像（MRI）研究从诊断开始，一直持续到青春期， 极其罕见这是一个关键的差距，因为青春期也是大脑发生深刻变化的时期。头脑 研究所自闭症表型组项目（APP）于2006年启动，旨在发现多层次的表型信息 从而能够定义ASD的临床上有意义的亚型。近300个家庭已经完成了初步的 成功的MRI检查。该APP包括所有严重程度的自闭症儿童， 焦虑和智力残疾等病症。患有ASD的儿童和年龄匹配的典型发育 对照组在2-3.5岁时进行第一次MRI，在~4岁和~12岁之间进行最多3次额外扫描; 773次MRI 扫描结果已经采集。我们建议将这项研究扩展到青春期中期的第五个时间点（14-17 年）。这项研究的一个指导性主题是，大脑发育的不同轨迹将区分子集 这些差异在孩子进入青春期时会变得更加明显， 这与青春期的发育相吻合。因为我们已经进行了基于儿科医生的坦纳分期， 多个时间点，我们将能够评估青春期如何影响这些发展的出现， 所有目标的大脑差异。利用获得的大量纵向结构MRI数据 到目前为止，我们将使用结构协方差分析和其他网络水平的战略，以评估发展 在几个特定领域的网络灰质结构的差异。专注于内在连通性 网络牵连在自闭症的三重网络模型，我们预测减少的幅度和程度的显着性 ASD患者的神经网络和中央执行网络在默认模式下存在较大程度的前-后解耦 网络杏仁核是一个大脑区域，一直被报道在ASD中被改变。我们之前的核磁共振成像和 尸检研究表明，在伴有增大的自闭症患者中，杏仁核的生长轨迹异常 在青春期萎缩。我们将研究杏仁核的纵向生长， 假设它在ASD的青春期经历萎缩。我们假设，这优先涉及 那些患有共同发生的焦虑症的人，不同于患有焦虑症的青少年，但不是ASD。我们将 还解决了关键的研究不足的问题，什么神经改变区分自闭症儿童， 没有智力障碍的人我们将研究大脑区域和相关网络的成熟， 智力和语言功能，以探索ASD儿童和低言语/认知 与那些语言/认知表现正常的人相比。最后，我们将评估自闭症的轨迹， 严重程度变化到青春期中期，并探讨这些变化的神经生物学基础。我们 预测显著性网络中的持续变化将与随着时间的推移而增加的严重性相关。

Adolescence is a complex time of heightened self-consciousness, risk taking and peer orientation which may be especially challenging for teens diagnosed with autism spectrum disorder (ASD). Longitudinal magnetic resonance imaging (MRI) studies of children with ASD that begin at diagnosis and extend into adolescence are extremely rare. This is a critical gap since adolescence is also a period of profound brain changes. The MIND Institute Autism Phenome Project (APP) was initiated in 2006 to discover multilevel phenotypic information enabling definition of clinically meaningful subtypes of ASD. Nearly 300 families have completed an initial assessment with successful MRI. The APP includes autistic children with all severity levels and co-occurring conditions such as anxiety and intellectual disability. Children with ASD and age-matched typically developing controls had their first MRI at 2-3.5 years of age and up to 3 additional scans between ~4 and ~12; 773 MRI scans have been acquired. We propose to extend this study to a 5th time point in middle adolescence (14-17 years). A guiding theme of this research is that different trajectories of brain development will differentiate subsets of children with ASD and some of these differences will become most apparent as the child enters adolescence, which coincides with pubertal development. Because we have carried out pediatrician-based Tanner staging at multiple time points, we will be able to evaluate how puberty influences the emergence of these developmental brain differences across all aims. Capitalizing on the large amount of longitudinal structural MRI data acquired to date, we will use structural covariance analysis and other network level strategies to evaluate developmental differences in gray matter structure across several domain specific networks. Focusing on intrinsic connectivity networks implicated in the triple network model of autism, we predict reduced magnitude and extent of salience and central executive networks in ASD and greater extent with anterior-posterior decoupling in the default mode network. The amygdala is a brain region consistently reported to be altered in ASD. Our previous MRI and postmortem research indicate that there is an abnormal trajectory of amygdala growth in autism with enlargement early on and atrophy in adolescence. We will investigate longitudinal growth of the amygdala to test the hypothesis that it undergoes atrophy in adolescence in ASD. We hypothesize that this preferentially involves those with a form of co-occurring anxiety disorder and is different from teens with anxiety but not ASD. We will also address the critical under-studied question of what neural alterations differentiate children with ASD with, and without, intellectual disability. We will investigate the maturation of brain regions and networks associated with intellectual and language function to explore differences between children with ASD and low verbal/cognitive performance from those with normal verbal/cognitive performance. Finally, we will evaluate trajectories of autism severity change into mid adolescence and explore the neurobiological underpinnings of these changes. We predict that persistent alterations in the salience network will be associated with increased severity over time.