Brain and Behavioral Development in Autism Spectrum Disorder

自闭症谱系障碍的大脑和行为发育

• 批准号: 10677001
• 负责人: David G Amaral
• 金额: $ 79.55万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677001
• 关键词: 11 year old; 12 year old; 5 year old; Address; Adolescence; Adolescent; Age; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Atrophic; Autopsy; Behavior; Behavioral; Biological; Brain; Brain region; Characteristics; Child; Clinical; Complex; Conscious; Coupling; Cross-Sectional Studies; Data; Development; Diagnosis; Diagnostic; Dorsal; Education; Exhibits; Face Processing; Family; Goals; Growth; Individual; Insula of Reil; Intellectual functioning disability; Knowledge; Language; Link; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Monitor; Motor Cortex; Neurobiology; Pattern; Phenotype; Puberty; Reporting; Research; Risk Taking; Scanning; Severities; Staging; Structure; Subgroup; Symptoms; Teenagers; Testing; Thick; Time; Visual Cortex; adolescent with autism spectrum disorder; age effect; anxiety spectrum disorders; anxiety symptoms; autism spectrum disorder; autistic; autistic children; cognitive performance; cohort; comparison group; executive function; gray matter; imaging study; improved; individuals with autism spectrum disorder; network models; neural; neural network; novel; pediatrician; peer; phenome; programs; sex; verbal

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.

青春期是一个高度自我意识、冒险和同伴取向的复杂时期，这可能是 对于被诊断为自闭症谱系障碍(ASD)的青少年来说尤其具有挑战性。纵向磁性 对ASD儿童的磁共振成像(MRI)研究从诊断开始一直延伸到青春期 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。心智 研究所自闭症表型组项目(APP)于2006年发起，旨在发现多层次的表型信息 能够定义具有临床意义的ASD亚型。近300个家庭完成了初步的 通过成功的核磁共振进行评估。该应用程序包括所有严重程度和共生的自闭症儿童 焦虑和智力残疾等病症。患有自闭症和年龄匹配的儿童典型发育 对照组在2-3.5岁时进行了第一次核磁共振检查，并在~4岁至~12岁之间进行了至多3次额外扫描；773次核磁共振检查 已经获取了扫描结果。我们建议将这项研究扩展到青春期中期(14-17岁)的第五个时间点 年)。这项研究的一个指导性主题是，不同的大脑发育轨迹将区分不同的亚群 随着儿童进入青春期，其中一些差异将变得最为明显， 这恰逢青春期发育。因为我们已经在儿科医生的基础上进行了Tanner分期 多个时间点，我们将能够评估青春期如何影响这些发育的出现 所有目标的大脑差异。利用获得的大量纵向结构磁共振数据 到目前为止，我们将使用结构协方差分析和其他网络层面的策略来评估发展 几个域特定网络中灰质结构的差异。关注内在连通性 在自闭症的三重网络模型中，我们预测显著程度和程度会降低 以及ASD中的中央执行网络，以及默认模式下的更大程度的前后脱钩 网络。杏仁核是一个大脑区域，据报道，ASD患者的大脑区域一直处于改变状态。我们之前的核磁共振和 尸检研究表明，自闭症患者杏仁核有异常生长轨迹，并伴有肿大。 早期和青春期萎缩。我们将研究杏仁核的纵向生长，以测试 ASD患者在青春期经历萎缩的假说。我们假设这优先涉及到 这些人患有某种形式的共生焦虑症，不同于患有焦虑但不是自闭症的青少年。我们会 也解决了研究不足的关键问题，即哪些神经变化将患有自闭症的儿童区分开来， 而不是智力残疾。我们将研究大脑区域和相关网络的成熟 用智力和语言功能探讨自闭症儿童与低言语/认知能力儿童的差异 语言/认知能力正常的人的表现。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，并探索这些变化的神经生物学基础。我们 预测显著网络中的持续变化将随着时间的推移与严重性的增加相关联。