Neural signatures of outcome in preschoolers with autism

患有自闭症的学龄前儿童的神经特征

• 批准号: 10442708
• 负责人: Adriana Di Martino
• 金额: $ 67.29万
• 依托单位: CHILD MIND INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-21 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442708
• 关键词: Acceleration; Adaptive Behaviors; Address; Adult; Age; Age Months; Anisotropy; Autism Diagnosis; Behavioral; Brain; Brain imaging; Child; Childhood; Clinical; Corpus striatum structure; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Dissection; Enrollment; Functional Magnetic Resonance Imaging; Goals; Heterogeneity; Image; Impairment; Individual; Investigation; Knowledge; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Methods; Motor; Neurobiology; Nursery Schools; Outcome; Parents; Parietal; Pattern; Phenotype; Predictive Value; Process; Prognosis; Prognostic Marker; Prospective Studies; Psychopathology; Reporting; Resolution; Rest; Role; Sampling; School-Age Population; Science; Sensory; Severities; Sleep; Stratification; Testing; Time; Work; adult with autism spectrum disorder; associated symptom; autism diagnostic observation schedule; autism spectrum disorder; autistic children; behavior observation; brain behavior; clinical diagnosis; common symptom; comorbidity; connectome; data de-identification; design; functional outcomes; improved; indexing; individuals with autism spectrum disorder; interest; longitudinal course; motor symptom; neural; neural circuit; neural correlate; outcome prediction; prospective; putamen; repetitive behavior; social communication; verbal; young adult

Objective. This proposal has the important goal of furthering our understanding of the longitudinal course of autism spectrum disorder (ASD). It is motivated by the urgent need for early prognostic markers able to explain the extensive heterogeneity of ASD outcomes. To this end, we propose a longitudinal study of young children with ASD (2-3 years) to identify the neurobiological underpinnings of early developmental changes in restricted repetitive behavior/interests (RRB) – one of the most clinically impairing aspects of ASD - and their predictive contribution to later function. The proposal builds on the confluence of related findings and our own work including: 1) clinical evidence that RRB changes over the age window between ~29 and 42 months are prognostic markers of ASD adult functioning; and 2) advances in brain developmental functional connectomics that allow investigations of neural circuits in preschoolers with ASD using natural sleep MRI. We specifically aim to test 1) whether changes from 24-36 to 36-48 months-of-age (T1, T2) in the intrinsic functional connectivity (iFC) of somatomotor (SM) striatal-cortical circuitry are associated with changes in the repetitive sensory motor (RSM) subdomain of RRB; and 2) whether these early brain-behavioral changes predict later (age: 48-60 months, T3) adaptive functioning. Exploratory aims will examine the potential contributions of structural connectivity changes in striatal-cortical tracts, and test whole-brain iFC employing unbiased connectome-wide association. Finally, we will explore the value of an alternative, data-driven hierarchical clustering approach to characterizing outcomes based upon multiple clinical dimensions at T3. Methods. We anticipate obtaining complete T1 and T2 brain-behavioral data from 100 preschoolers with ASD enrolled at age 24-36 months and followed prospectively on a yearly basis. At T1 and T2, preschoolers will undergo natural sleep imaging with state-of-the-art MRI (high resolution T1- and T2-weighted structural MRI, multiband resting state fMRI (R- fMRI), and when possible, diffusion tensor) and phenotypic assessments rigorously selected to deeply phenotype a range of ASD core and associated symptoms. To examine the predictive value of iFC and RSM changes (i.e., T1-T2) to later function, children will be re-evaluated at 48-60 months (T3). A partial list of assessments includes: Autism Diagnostic Observation Schedule-2, Behavioral Observation Social Communication Checklist, Repetitive Behavior Scale-Revised, clinician and parent measures of comorbid psychopathology and adaptive functioning. Brain-behavior analyses will primarily rely on R-fMRI, and explore diffusion tensor imaging. Significance. Findings will elucidate the neural correlates of changes in RSM at the earliest practical time following clinical diagnosis. They will provide a developmentally informed understanding of the neural underpinnings of outcomes, thus bringing the field closer to a neural stratification of individuals. Such knowledge is essential for developing neuroscientifically-informed treatments. Impact is maximized by sharing de-identified data with the NDAR and ABIDE yearly to accelerate scientific progress.

客观的。该提议的重要目标是进一步了解我们对纵向过程的理解 自闭症谱系障碍（ASD）。这是由于早期预后标记的迫切需要解释 ASD结果的广泛异质性。为此，我们提出了对幼儿的纵向研究 与ASD（2 - 3年）一起确定受限早期发育变化的神经生物学基础 重复行为/兴趣（RRB） - ASD临床上最受损的方面之一 - 及其预测性 对以后功能的贡献。该提案建立在相关发现和我们自己的工作的基础上 包括：1）临床证据表明，RRB在年龄窗口范围内发生〜29至42个月之间的变化为 ASD成人功能的预后标记； 2）大脑发育功能连接的进步 这允许使用自然睡眠MRI对ASD的学龄前儿童中的神经回路进行研究。我们特别针对 测试1）在固有功能连通性中，是否从24-36变为36-48个月（T1，T2） 体育体（SM）纹状体皮质电路的（IFC）与重复的感觉电动机的变化有关 （RSM）RRB的子域； 2）这些早期的大脑行为变化是否稍后预测（年龄：48-60 月份，T3）自适应功能。探索目的将检查结构的潜在贡献 纹状体皮层区域的连通性变化，并使用无偏连接组的全脑IFC测试全脑 协会。最后，我们将探讨一种替代，数据驱动的分层聚类方法的价值 根据T3处的多个临床维度来表征结局。方法。我们预计会获得 从100名ASD招收的100名学龄前儿童的T1和T2脑行为数据24-36个月招募 预期每年都有。在T1和T2，学龄前儿童将与 最先进的MRI（高分辨率T1-和T2加权结构MRI，多型和静止状态fMRI（r-） fMRI），并在可能的情况下进行扩散张量）和表型评估严格选择 表型一系列ASD核心和相关符号。检查IFC和RSM的预测值 更改（即T1-T2）以后功能，将在48-60个月（T3）重新评估儿童。部分列表 评估包括：自闭症诊断观察附表2，行为观察社会 沟通清单，重复行为量表重新定义，合并症的临床和父母度量 心理病理学和自适应功能。脑行为分析将主要依靠R-FMRI，并探索 扩散张量成像。意义。发现将阐明RSM变化的神经相关性 临床诊断后最早的实际时间。他们将提供发达的知情理解 结局的神经元基础，从而使该领域更接近个体的神经元分层。 这种知识对于开发神经科学知识的治疗至关重要。影响最大 与NDAR共享识别数据，并遵守年度，以加速科学进步。

项目成果

Towards robust and replicable sex differences in the intrinsic brain function of autism.

• DOI: 10.1186/s13229-021-00415-z
• 发表时间: 2021-03-01
• 期刊: Molecular autism
• 影响因子: 6.2
• 作者: Floris DL;Filho JOA;Lai MC;Giavasis S;Oldehinkel M;Mennes M;Charman T;Tillmann J;Dumas G;Ecker C;Dell'Acqua F;Banaschewski T;Moessnang C;Baron-Cohen S;Durston S;Loth E;Murphy DGM;Buitelaar JK;Beckmann CF;Milham MP;Di Martino A
• 通讯作者: Di Martino A

Predicting multiscan MRI outcomes in children with neurodevelopmental conditions following MRI simulator training.

• DOI: 10.1016/j.dcn.2021.101009
• 发表时间: 2021-12
• 期刊: Developmental cognitive neuroscience
• 影响因子: 4.7
• 作者: Simhal AK;Filho JOA;Segura P;Cloud J;Petkova E;Gallagher R;Castellanos FX;Colcombe S;Milham MP;Di Martino A
• 通讯作者: Di Martino A

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

• DOI: 10.1186/s13229-022-00536-z
• 发表时间: 2023-02-14
• 期刊: Molecular autism
• 影响因子: 6.2

Atypical Integration of Sensory-to-Transmodal Functional Systems Mediates Symptom Severity in Autism.

• DOI: 10.3389/fpsyt.2021.699813
• 发表时间: 2021
• 期刊: Frontiers in psychiatry
• 影响因子: 4.7
• 作者: Park S;Haak KV;Cho HB;Valk SL;Bethlehem RAI;Milham MP;Bernhardt BC;Di Martino A;Hong SJ
• 通讯作者: Hong SJ