The fusiform and amygalda in the pathobiology of autism

描述（由申请人提供）：面部识别技能是有效社交技能的重要基础。患有自闭症谱系障碍（ASD：自闭症、阿斯伯格综合症和广泛性发育障碍，未作特别说明）的人在识别面孔的方式上有各种缺陷，包括依赖于个体面部特征（尤其是嘴巴而不是眼睛），而不是整体处理面孔的典型模式。功能性磁共振成像（fMRI）研究表明，ASD患者的两个大脑结构——左侧杏仁核和右侧梭状回的外侧部分功能异常。这些发现尤其重要，因为它们是第一个被多个实验室独立证实与自闭症病理生物学有关的大脑区域。这两种结构在asd病理生物学中的作用通过死后脑研究和常规结构MRI的大体神经解剖学研究得到进一步证实。然而，在正常发育的人和自闭症患者中，关于调节这些大脑区域活动的参数，仍有许多重要的问题有待回答。本R01应用程序中的实验旨在通过系统的一系列功能磁共振成像研究来扩展我们在该领域的现有知识。这些研究利用红外眼动追踪技术来研究扫描路径与大脑区域活动之间的关系。这些研究涉及系统地操纵参数，这些参数被认为可以调节这两个大脑区域的活动水平以及它们之间的功能连接。总的来说，我们提出了一系列的4项fMRI研究，每项研究都涉及18名ASD患者和18名典型发展对照组（tdc）的比较。我们假设ASD中梭状回和杏仁核的低激活是由以下因素介导的：(1)注意和知觉焦点的变化；(2)刺激参数的各个方面（如面部情绪程度）；(3)当信息通过皮层和皮层下视觉通路传入时，梭状回和杏仁核之间的相互作用。

DESCRIPTION (provided by applicant): Face recognition skills are an important substrate of effective social skills. Persons with an autism spectrum disorder (ASD: autism, asperger syndrome and pervasive developmental disorder not otherwise specified) have a variety of deficits in the manner in which they recognize faces, including a reliance on individual facial features (particularly the mouth and not eyes) rather than the typical pattern of processing faces holistically. Functional magnetic resonance imaging studies (fMRI) of face perception in ASD have shown that two brain structures - the left amygdala and the lateral aspect of the right fusiform gyrus are functionally abnormal. These findings are especially significant because they are the first brain areas to be independently confirmed by multiple labs as involved in the pathobiology of ASDs. The role of these two structures in pathobiology of ASDs is further substantiated by postmortem brain studies and gross neuroanatomical studies using conventional structural MRI. However, there remain many important questions to be answered about the parameters that modulate activity in these brain regions, both in typically developing persons and in persons with an ASD. The experiments in this R01 application are designed to extend our current knowledge in this area through a systematic series of fMRI studies. These studies make use of infra red eye tracking technology to study the relationship between scan paths and regional brain activity. These studies involve systematic manipulation of parameters that are believed to modulate level of activity in these 2 brain areas and the functional connectivity between them. In total, we propose a link series of 4 fMRI studies, each involving a comparison between 18 persons with an ASD and 18 typically developing controls (TDCs). We hypothesis that the hypoactivation of the fusiform and amygdala in ASD is mediated by (1) variation in attention and focus of perception; (2) aspects of the stimulus parameters (e.g., degree of facial emotion); and (3) interactions between the fusiform and amygdala as information comes through cortical and subcortical visual pathways.