Integrity and Dynamic Processing Efficiency of Networks in ASD

描述（由申请人提供）：越来越多的功能连接MRI（fcMRI）和扩散张量成像（DTI）文献表明，自闭症谱系障碍（ASD）的认知、社交和感觉运动障碍与大脑网络连接受损相关。然而，迄今为止，很少有ASD研究将功能和解剖连接的测量结合起来。更重要的是，没有研究将这些与脑磁图（MEG）提供的动态处理措施相结合。我们建议使用fcMRI，DTI和MEG的全面调查ASD的连接，选择一个任务范式，以确定一个视觉，词汇语义，执行和电机（VLSEM）电路的一组示例性的网络节点。本研究将收集60名ASD青少年和60名正常发育（TD）青少年的数据，以实现四个具体目标：（1）使用功能磁共振成像识别词汇语义决策过程中VLSEM回路的节点，并检查该回路内以及节点与其余大脑之间的功能连接。(2)为了研究VLSEM电路的动态时空特性，使用MEG进行时域和时频分析，包括在几个频带中的锁相共振荡。(3)使用概率性DTI纤维束成像检查VLSEM回路内连接的解剖完整性，并测试fcMRI、MEG和DTI测量之间的联系。(4)研究ASD组的功能和解剖连接以及动态处理与诊断和神经心理学测量的关系。这项研究将有助于多模态成像证据，以改善和全面了解ASD的脑网络异常。这些证据对于ASD的生物标志物的鉴定尤其重要，包括那些可以区分疾病的生物亚型的生物标志物。对寻找生物标志物的贡献将具有公共健康益处，因为这样的生物标志物对于鉴定遗传和免疫缺陷是至关重要的。 需要针对性治疗的其他ASD原因。

DESCRIPTION (provided by applicant): A growing functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) literature suggests that cognitive, sociocommunicative, and sensorimotor impairments in autism spectrum disorders (ASD) are associated with impaired brain network connectivity. However few ASD studies to date have combined measures of functional and anatomical connectivity. Even more importantly, there are no studies combining these with measures of dynamic processing, as provided by magnetoencephalography (MEG). We propose to use fcMRI, DTI, and MEG for a comprehensive investigation of connectivity in ASD, selecting a task paradigm to identify a visual, lexico-semantic, executive, and motor (VLSEM) circuit for an exemplary set of network nodes. Data from sixty adolescents with ASD and 60 matched typically developing (TD) participants will be acquired to pursue four specific aims: (1) To identify nodes of a VLSEM circuit using fMRI during lexical-semantic decision and to examine the functional connectivity within this circuit and between nodes and the remaining brain. (2) To examine the dynamic, spatiotemporal characteristics of the VLSEM circuit, using MEG in time-domain and time-frequency analyses including phase-locked co-oscillation in several frequency bands. (3) To examine the anatomical integrity of connections within the VLSEM circuit using probabilistic DTI tractography, and to test for links between fcMRI, MEG, and DTI measures. (4) To examine the relation of functional and anatomical connectivity as well as dynamic processing with diagnostic and neuropsychological measures in the ASD group. The study will contribute multimodal imaging evidence for an improved and comprehensive understanding of brain network abnormalities in ASD. Such evidence will be particularly important for the identification of biomarkers of ASD, including those which may distinguish biological subtypes of the disorder. The contribution to the search for biomarkers will have public health benefit because such biomarkers will be crucial for the identification of genetic and other causes of ASD needed for targeted treatment.