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.

青春期是一个复杂的自我意识，冒险和同伴方向的复杂时期 对于被诊断出患有自闭症谱系障碍（ASD）的青少年特别具有挑战性的挑战。纵向磁性 对诊断和延伸到青春期开始的ASD儿童的共振成像（MRI）研究是 极为罕见。这是一个关键的差距，因为青春期也是大脑变化的时期。头脑 研究所自闭症现象项目（APP）于2006年启动，以发现多级表型信息 实现ASD临床上有意义的亚型的定义。近300个家庭已经完成了一个初始 成功的MRI评估。该应用包括具有所有严重程度和同时发生的自闭症儿童 焦虑和智力残疾等疾病。患有ASD和年龄匹配的孩子通常会发展 对照组在2-3.5岁时获得了第一个MRI，最多3至〜4至12之间的另外3次扫描； 773 MRI 扫描已被获取。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）。这项研究的指导主题是，大脑发育的不同轨迹将使子集有区别 随着儿童进入青春期，患有ASD和其中一些差异的儿童将变得最明显 这与青春期的发展一致。因为我们在儿科医生进行了制革厂演出 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。利用获取的大量纵向结构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别策略来评估发展 多个域特有网络之间的灰质结构的差异。专注于固有连通性 与自闭症三重网络模型有关的网络，我们预测了显着性的幅度和程度降低 和ASD的中央执行网络和更大程度的默认模式下的前后脱钩 网络。杏仁核是据报道在ASD中改变的大脑区域。我们以前的MRI和 验尸研究表明，自闭症患有杏仁核增长的异常轨迹随着增大 早期和青春期萎缩。我们将研究杏仁核的纵向生长，以测试 假设它在ASD的青春期经历了萎缩。我们假设这优先涉及 那些具有同时发生焦虑症的形式的人，与焦虑症的青少年不同，但没有ASD。我们将 还解决了一个关键的研究不足的问题，即哪些神经改变使儿童与ASD不同， 没有智力残疾。我们将研究大脑区域和相关网络的成熟 具有智力和语言功能来探索ASD和低口头/认知儿童之间的差异 言语/认知表现正常的表现。最后，我们将评估自闭症的轨迹 严重性变化为青春期中间，并探索这些变化的神经生物学基础。我们 预测显着性网络的持续变化将随着时间的推移的严重程度增加而增加。