Multimodal Neuroimaging of White Matter in Autism

自闭症白质的多模态神经影像

基本信息

批准号：
7034329
负责人：
MARTHA R. HERBERT
金额：
$ 64.87万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-15 至 2010-02-28
项目状态：
已结题

项目摘要

Autism is a behaviorally defined but biologically heterogeneous disorder, involving a cluster of impairments in language, social interaction and behavior. Large brains are common in autism, but their underlying tissue microstructure and their impact on the autistic phenotype are not understood. This proposal is based on the model that increased white matter volume is related to impaired connectivity and to underlying core processing abnormalities in autism. To test this model we will pursue our prior findings that white matter enlargement drives large brains and is localized to the later-myelinating radiate zone (the white matter closest to the cerebral cortex). We will use multispectral MRI to gain systematic information about the tissue microstructure and patterns of structural connectivity of enlarged white matter in autism, and we will relate these findings to cognitive and behavioral phenotype and to genome data. Forty autistic and forty typically developing boys ages 6-10 will receive a cognitive and behavioral battery and genetic studies. Specific Aim 1: We will construct a convergent multimodal tissue microstructure profile, coregistering boundaries from whole-brain segmentation and parcellation with estimated tissue parameters (T1, T2*, PD) magnetic resonance and diffusion tensor (DTI) data. Data will be analyzed for patterns discernable in multiple measures that may illuminate altered tissue microstructure. Specific Aim 2: We will investigate structural connectivity utilizing DTI tract segmentation and multimodal tissue profiling of segmented tracts. Specific Aim 3: We will test brain-connectivity-processing-endophenotype correlations, including genome data. We predict 1) that perturbations of volume and tissue integrity will be correlated with each other, and will be distributed by zone-more in later-myelinating radiate than deep zone white matter rather than by tract or neural system; 2) that measures of impaired complex processing (e.g., central coherence) will a) correlate with measures of widespread anatomical changes (e.g., white matter increase), b) be associated with autism even if regional brain changes are absent, and c) be associated in severity with severity of specific behavioral endophenotypes as well as of widespread anatomical abnormalities, and 3) that common anatomical and behavioral findings will be associated with varied genome changes. Our study design will also detect alternate outcomes and will yield data relevant for multiple levels of translational research.

自闭症是一种行为上定义但在生物学上异质性疾病，涉及语言，社会互动和行为的一系列障碍。大脑在自闭症中很常见，但是它们的潜在组织微观结构及其对自闭症表型的影响尚不清楚。该建议基于以下模型：增加的白质体积与自闭症中的连通性和潜在的核心处理异常有关。为了测试该模型，我们将追求先前的发现，即白质增大会驱动大脑，并局部属于腹膜辐射区（最接近大脑皮层的白质）。我们将使用多光谱MRI来获取有关自闭症中白质的组织微观结构和结构连通性模式的系统信息，我们将联系这些发现对认知和行为表型以及基因组数据。四十个自闭症和四十个通常是6-10岁的男孩将接受认知和行为电池和遗传研究。具体目的1：我们将构建收敛的多模式组织微观结构曲线，从全脑分割和估计组织参数（T1，T2*，PD）磁共振和扩散量张量（DTI）数据的核心边界。数据将在多种措施中分析可能阐明组织微观结构的多种措施中的模式。具体目标2：我们将利用DTI段分割和分段区域的多模式组织分析来研究结构连通性。特定目标3：我们将测试包括基因组数据在内的脑连接性处理 - 内形型相关性。我们预测1）体积和组织完整性的扰动将彼此相关，并将通过区域 - 摩尔分布在以后的层次辐射中，而不是深层白质，而不是通过区域或神经系统； 2) that measures of impaired complex processing (e.g., central coherence) will a) correlate with measures of widespread anatomical changes (e.g., white matter increase), b) be associated with autism even if regional brain changes are absent, and c) be associated in severity with severity of specific behavioral endophenotypes as well as of widespread anatomical abnormalities, and 3) that common anatomical and行为发现将与不同的基因组变化有关。我们的研究设计还将检测到替代结果，并产生与多个转化研究相关的数据。