MRI STUDIES OF EARLY BRAIN DEVELOPMENT IN AUTISM

自闭症早期大脑发育的 MRI 研究

• 批准号: 7681642
• 负责人: ERIC COURCHESNE
• 金额: $ 36.21万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7681642
• 关键词: 4 year old; Affect; Age; Age-Months; Age-Years; Amygdaloid structure; Anatomy; Anisotropy; Apoptosis; Area; Autistic Disorder; Basic Science; Behavior; Behavioral; Behavioral Symptoms; Bioinformatics; Biological; Biological Markers; Biology; Biometry; Biostatistics Core; Birth; Brain; Brain region; Cell model; Cerebellum; Cerebrum; Clinical; Cognitive; Collaborations; Development; Developmental Delay Disorders; Diagnostic; Disease; Disruption; Emotional; Evaluation; Fingerprint; Functional disorder; Genes; Genetic; Goals; Gray unit of radiation dose; Growth; Head circumference; Heterogeneity; Histocompatibility Testing; Infant; Investigation; Knowledge; Language; Life; Limbic System; MRI Scans; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mediating; Methods; Multivariate Analysis; Neurophysiology - biologic function; Outcome; Pathway interactions; Phenotype; Procedures; Process; Prospective Studies; Protocols documentation; Publishing; Rate; Reporting; Retrospective Studies; Risk; Severities; Signal Transduction; Staging; Stem cells; Structure; Susceptibility Gene; Temporal Lobe; Therapeutic; Thick; Time; Variant; Work; age related; autistic behaviour; base; brain size; clinical phenotype; cognitive function; concept; deviant; endophenotype; genetic analysis; genetic association; gray matter; insight; interest; member; neural circuit; neurogenesis; novel; prospective; relating to nervous system; social; tool; white matter

Early brain overgrowth is a recently identified, but not yet directly measured, phenomenon in autism. Direct MRI measurement of the young autistic brain comes from five studies that found brain overgrowth at mean study ages of 2.7 to 3.9 yrs. Affected brain regions mediate higher-order social, emotional, language and cognitive functions that characterize autism. MRI studies of early brain growth in autism are absent. Indirect evidence of brain growth in autism comes from retrospective analyses of head circumference (HC). In the first study to examine the question, we reported that HC was normal average to slightly smaller than normal at birth in those who later manifested autism, but by about 12 months HC was abnormally large. Inferring brain growth rates from age-related changes in HC and placing that with the five MRI brain size studies of 2 to 4 year olds led us to the hypothesis that autism may involve a brief and agedelimited period of abnormal brain overgrowth during the first two years of life. According to the only two existent prospective studies of autism, 12 months is also approximately the first age at which autistic behavioral abnormalities first become detectable. The formation of neural circuitry is at its most exuberant and vulnerable stage during this period of development. Aberrant connectivity and neural dysfunction resulting from disruptions to this process may be key to the development of autistic behaviors. Thus, the first years of life in autism offer a unique chance to track the simultaneous emerging expression of the autistic anatomical and clinical phenotype and establish their relationship to each other and to underlying causal mechanisms, such as genes and genetic pathways that affect brain growth. We will identify early brain growth biomarkers in ASD by longitudinally MRI scanning infants at-risk for ASD, infants at-risk for developmental delay and typical infants at 12 and 24 months. We will obtain region-specific measures of volume, area, cortical thickness, fractional anisotropy and apparent diffusivity coefficient and developmental change values. Detailed anatomic maps of each region will be derived for each infant at each age. At age 36 months, a final best estimate diagnostic evaluation will identify which atrisk infants are ASD, DD or other. MRI results from these ASD and DD infants and typical infants will be statistically compared and early ASD brain growth abnormalities identified. Anatomical measures will be identified that characterize and predict the early developmental clinical phenotype of ASD that Cores B and C in collaboration with the Integrated Biostatistics Core D will identify. We will work with Project 4 and the Integrated Biostatistics Core D to use the brain growth biomarkers to discover overgrowth susceptibility genes and pathways. With Core D, we will identify separate clusters of distinctly different brain maldevelopment phenotypes among the ASD infants.

早期的大脑过度生长是一种自闭症中最近发现但尚未直接测量的现象。 年轻自闭症大脑的直接MRI测量来自五项研究，发现大脑过度生长 平均研究年龄为2.7至3.9岁。受影响的大脑区域介导了高阶社交，情感，语言 和特征自闭症的认知功能。缺乏对自闭症早期大脑生长的MRI研究。 自闭症大脑生长的间接证据来自对头部的回顾性分析 周长（HC）。在首次研究这个问题的研究中，我们报告说HC是正常的平均 在后来表现自闭症的人中，出生时出生时略小，但大约12个月的HC是 异常大。从HC中与年龄相关的变化推断大脑生长速率，并将其放置在五个 2至4岁的MRI脑大小研究使我们提出了一个假设，即自闭症可能涉及短暂且年龄段的人 在生命的头两年中，异常大脑过度生长的时期。 根据仅有的两项自闭症前瞻性研究，12个月也大约是 自闭症行为异常首先可以检测到的第一个年龄。神经回路的形成 在这一发展时期，处于最旺盛，最脆弱的阶段。异常连接性和 该过程中断导致的神经功能障碍可能是自闭症发展的关键 行为。因此，自闭症生命的头几年为跟踪同时出现的独特机会 自闭症解剖学和临床表型的表达，并建立它们的关系 为了基本的因果机制，例如影响脑生长的基因和遗传途径。 我们将通过纵向的MRI扫描在ASD中识别ASD的早期大脑生长生物标志物 对于ASD，婴儿在12和24个月时以发育延迟和典型婴儿的危险。我们将获得 区域特定的体积，面积，皮质厚度，分数各向异性和明显扩散率的测量 系数和发展变化值。将得出每个区域的详细解剖图 每个婴儿的每个婴儿。在36个月时，最终的最佳估计诊断评估将确定哪个Atrisk 婴儿是ASD，DD或其他。这些ASD和DD婴儿以及典型婴儿的MRI结果将是 统计上比较和早期ASD脑生长异常。解剖措施将是 确定表征并预测核心B和 C将与综合生物统计学核心D合作确定。我们将与项目4和 综合生物统计学核心D用于使用大脑生长生物标志物发现过度生长的敏感性 基因和途径。使用核心D，我们将确定大脑明显不同的单独簇 ASD婴儿中的MALDEVEVERMENT表型。