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: 2424379
• 负责人: Pauline A. Filipek
• 金额: $ 34.72万
• 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/2424379
• 关键词: adolescence (12-20); autism; 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：到了学龄期，人脑的正常生长速度会下降。 很明显，但这些最后阶段对 运动能力、语言能力、认知能力和社交能力与语言习得的关系 适应性行为。这些增长率反映了正常的微妙平衡 进行性和退行性的组织发生机制。发展中的 障碍可以成为研究大脑发育异常的模型，在 特殊的自闭症(AD)，其特征是 社会化、注意力、概念形成、语言和非语言 交流，以及仪式性的、坚持不懈的行为。调查员的 发育期阿尔茨海默病儿童早期MRI形态计量分析 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的大脑体积都出人意料地大 以及控制，这是由于过度的白质不成比例地 定位于颞区和顶后区，包括 角回、顶上小叶和视觉/关联区。 这些结果表明新皮质系统发育不良， 与一些经典的新皮质局部化理论一致。 调查人员建议：1)招募三个新的儿童队列 青春期早期，年龄在10.0岁到15.11岁之间，每个人N=30：a)自闭症 障碍，分为高智商(非语言智商70)和低智商(非语言智商70)AD 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，出生、发育和 病史以及正常、认知、语言和行为功能 (非语言智商；70)；2)复制调查者之前的形态测量 阿尔茨海默病队列中局限性异常白质体积的发现 执行两个顺序高分辨率三维中的第一个 (3)梯度回波T(1)加权MRI扫描。完全形态测量 分析将包括计算整个大脑、个体的体积 子结构和半球梯度。大脑皮层的一种新方法 然后将定位和分割应用于这些MRI扫描， 参考Brodnann建筑图并与介观模型兼容 神经系统层次结构图；3)检验假设 异常的神经系统功能障碍与语言和 AD患者的神经行为缺陷，与非言语智商无关；以及4) 进一步研究青春期对阿尔茨海默病脑发育的影响 三年后进行两次连续MRI扫描中的第二次 对这些AD和AD的重复形态测量和皮质分割分析 控制队列。