AUTISM--A MODEL OF ANOMALOUS NEURAL SYSTEMS DEVELOPMENT

自闭症——神经系统发育异常的模型

• 批准号: 2714624
• 负责人: Pauline A. Filipek
• 金额: $ 34.01万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2714624
• 关键词: adolescence (12-20); autism; behavioral /social science research tag; clinical research; developmental neurobiology; human puberty; human subject; longitudinal human study; magnetic resonance imaging; middle childhood (6-11); neuroanatomy

DESCRIPTION: By school age, the rate of normal human brain growth declines sharply, but these final phases are especially critical to the maturation of motor, linguistic, cognitive and social aptitudes in the acquisition of adaptive behaviors. These growth rates reflect a delicate balance of normal progressive and regressive histogenic mechanisms. The developmental disorders can be a model for study of anomalous brain development, in particular autistic disorder (AD), which is characterized by deficits in socialization, attention, concept formation, verbal and non-verbal communication, and ritualistic, perseverative behaviors. The investigator's prior MRI-based morphometric analysis in children with AD, developmental language disorders (DLD), non-autistic low IQ (NILIQ), and normal children have shown that both AD and DLD brains are unexpectantly larger in volume and controls which is due to excessive white matter disproportionately localized to the temporal and posterior parietal region, including the angular gyrus, superior parietal lobule, and visual/association regions. These results point to maldevelopment of neocortical systems and are consistent with some of the classic neocortical localization theories. The investigators propose: 1) To recruit three new cohorts of children in early adolescence, aged 10.0 through 15.11, N=30 in each: a) autistic disorder, divided into high IQ (nonverbal IQ70) and low (nonverbal IQ<70) AD cohort; b) nonautistic low IQ (nonverbal IQ<70); c) normal control volunteers are children with headaches, with normal birth, development, and medical histories, and normal, cognitive, linguistic and behavioral function (nonverbal IQ<70); 2) To replicate the investigator's previous morphometric findings of localized anomalous white matter volumes in the AD cohorts by performing the first of two sequential high-resolution three dimensional (3D) gradient echo T(1) - weighted MRI scans. Complete morphometric analysis will include computation of volume for whole brain, individual substructures, and hemisphere gradients. A new method of cortical localization and parcellation will then be applied to these MRI scans, reference to the Brodnann architectonic map and compatible with the Mesulem scheme of neurosystems hierarchy; 3) To test the hypothesis that the anomalous dysfunctional neurosystems are related to linguistic and neurobehavioral deficits in AD, independent of nonverbal IQ; and 4) To further investigate the effects of puberty on brain development in AD by performing a second of two sequential MRI scans three years later with repeated morphometric and cortical parcellation analysis on these AD and control cohorts.

描述：到了上学年龄，人类大脑正常发育的速度会下降。 尖锐，但这些最后阶段是特别重要的成熟， 运动，语言，认知和社会能力的收购， 适应行为 这些增长率反映了正常的 进行性和退行性组织发生机制。 发育 疾病可以成为研究异常大脑发育的模型， 特别是自闭症障碍（AD），其特征在于缺乏 社会化，注意，概念形成，言语和非言语 交流，仪式化，持续性行为。 研究者 先前基于MRI的AD儿童形态测量分析，发育 语言障碍（DLD）、非自闭症低智商（NILIQ）和正常儿童 已经表明AD和DLD的大脑体积都出乎意料的大 和控制，这是由于过量的白色物质不成比例 位于颞叶和后顶叶区域，包括 角回、上级顶叶小叶和视觉/联合区。 这些结果表明新皮层系统发育不良， 与一些经典的皮层定位理论相一致。 研究人员建议：1）招募三组新的儿童， 青春期早期，年龄10.0 - 15.11岁，每组N=30：a）自闭症 AD分为高智商（非语言智商70）和低智商（非语言智商<70） 队列; B）非自闭症低智商（非语言智商<70）; c）正常对照 志愿者是患有头痛的儿童，正常出生，发育， 病史和正常的认知、语言和行为功能 （非言语智商<70）; 2）重复研究者先前的形态测量 AD队列中局部异常白色物质体积的结果， 执行两个连续高分辨率三维中的第一个 (3D)梯度回波T（1）加权MRI扫描。 完全形态计量学 分析将包括计算全脑、个体 子结构和半球梯度。 一种新的皮质骨测量方法 然后将定位和分割应用于这些MRI扫描， 参考Brodnann构造图并与Mesulem兼容 神经系统层次结构的方案; 3）为了检验假设， 异常的功能失调的神经系统与语言和 AD中的神经行为缺陷，独立于非语言智商;以及4） 进一步研究青春期对AD大脑发育的影响， 三年后进行了两次连续MRI扫描中的第二次， 对这些AD进行重复的形态测量和皮质包裹分析， 对照组。