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: 10519038
• 负责人: David G Amaral
• 金额: $ 80.66万
• 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/10519038
• 关键词: 11 year old; 12 year old; 5 year old; Address; Adolescence; Adolescent; Age; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Atrophic; Autopsy; Behavioral; Biological; Brain; Brain region; Characteristics; Child; Clinical; Complex; Conscious; Coupling; Cross-Sectional Studies; Data; Development; Diagnosis; Diagnostic; Dorsal; Exhibits; Face Processing; Family; Goals; Growth; Individual; Institutes; Insula of Reil; Intellectual functioning disability; Knowledge; Language; Lead; 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; base; brain behavior; cognitive performance; cohort; comparison group; executive function; gray matter; imaging study; improved; individuals with autism spectrum disorder; network models; neural network; novel; pediatrician; peer; phenome; programs; relating to nervous system; sex

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.

青春期是一个自我意识增强、敢于冒险和同侪导向的复杂时期，这可能是 对于被诊断患有自闭症谱系障碍 (ASD) 的青少年来说尤其具有挑战性。纵向磁力 对自闭症谱系障碍 (ASD) 儿童进行的磁共振成像 (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。头脑 研究所自闭症表型项目 (APP) 于 2006 年启动，旨在发现多层次表型信息 能够定义具有临床意义的 ASD 亚型。近300个家庭已完成初步 通过成功的 MRI 进行评估。该应用程序包括所有严重程度和同时发生的自闭症儿童 焦虑和智力障碍等状况。患有自闭症谱系障碍 (ASD) 的儿童和年龄相匹配的典型发育儿童 对照组在 2-3.5 岁时进行了第一次 MRI 扫描，并在 ~4 岁至 ~12 岁之间进行了最多 3 次额外扫描；第773章 核磁共振成像 已获取扫描结果。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主题是大脑发育的不同轨迹将区分子集 患有自闭症谱系障碍 (ASD) 的儿童中，其中一些差异将在孩子进入青春期时变得最为明显， 这与青春期发育相吻合。因为我们已经在儿科医生的指导下进行了 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 MRI 数据 迄今为止，我们将使用结构协方差分析和其他网络级策略来评估发育 多个领域特定网络之间灰质结构的差异。注重内在的连通性 自闭症三重网络模型中涉及的网络，我们预测显着性的程度和程度会降低 自闭症谱系障碍 (ASD) 中的中枢执行网络以及更大范围内的默认模式下的前后解耦 网络。据报道，杏仁核是自闭症谱系障碍中发生改变的大脑区域。我们之前的 MRI 和 尸检研究表明自闭症患者的杏仁核生长轨迹异常并伴有增大 青春期早期和萎缩。我们将研究杏仁核的纵向生长来测试 假设自闭症谱系障碍 (ASD) 患者的青春期它会萎缩。我们假设这优先涉及 那些同时患有某种形式的焦虑症的人，与患有焦虑症但不属于自闭症谱系障碍的青少年不同。我们将 还解决了一个尚未得到充分研究的关键问题，即自闭症谱系障碍儿童的神经改变有何不同， 没有智力障碍。我们将研究相关大脑区域和网络的成熟程度 具有智力和语言功能，可探索患有自闭症谱系障碍（ASD）和语言/认知能力低下的儿童之间的差异 具有正常言语/认知表现的人的表现。最后，我们将评估自闭症的轨迹 青春期中期的严重程度变化并探索这些变化的神经生物学基础。我们 预测显着网络的持续变化将与随着时间的推移而增加的严重性相关。