Amygdala Connectivity in Autism Spectrum Disorder

描述（由申请人提供）：自闭症谱系障碍（ASD）是一组在生命最初2-4年被诊断出的神经发育疾病，包括社会互动和沟通方面的缺陷。尽管许多大脑区域可能与ASD有关，但杏仁核一直是一个非常有趣的区域，因为它在情绪行为中的作用以及它与其他大脑区域的众多联系也与ASD有关。在ASD受试者中已经证实了异常的杏仁核功能，初步研究已经在ASD成人的死后组织中发现了改变的杏仁核神经解剖学。此外，一些磁共振成像（MRI）研究表明，年轻的ASD受试者的杏仁核增大，而且这种增大发生在生命早期。最近的报告不仅证实了这种扩大，而且还确定了自闭症儿童在生命最初几年的杏仁核生长的多种模式。这些结果表明，杏仁核可能是ASD异常大脑网络的中心，并且不同组的ASD杏仁核病理可能不同。这些发现还提出了一种可能性，即在自闭症患者中，杏仁核和其他大脑区域之间的连接模式发生了改变。然而，与杏仁核相关的白质通路的潜在改变尚未得到彻底的研究。弥散张量成像（DTI）允许在体内可视化和脑通路的调查。DTI研究已经开始确定成人ASD大脑中的白质异常，但没有研究调查ASD症状最初出现和杏仁核异常增大最明显的生命早期杏仁核连接。这项拟议的研究将利用DTI来调查大型纵向组学龄前ASD儿童和典型发育对照儿童的杏仁核连通性。通过多年来检查幼儿杏仁核与杏仁核之间连接的完整性，这项拟议的研究将对我们对ASD中杏仁核异常的理解做出重大贡献。此外，通过在一大批广泛表型的ASD儿童中检测白质通路，本提案旨在进一步确定ASD中特定的神经病理学亚型。

DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions diagnosed in the first 2-4 years of life which includes deficits in social interaction and communication. Although many brain regions are likely involved in ASD, the amygdala has been an area of great interest due to its role in emotional behavior and its numerous connections to other brain regions also implicated in ASD. Abnormal amygdala function has been demonstrated in ASD subjects and initial studies have identified altered amygdala neuroanatomy in post- mortem tissue from ASD adults. In addition, several magnetic resonance imaging (MRI) studies demonstrate that the amygdala is enlarged in young ASD subjects and that this enlargement occurs early in life. Recent reports not only confirm this enlargement but have also identified multiple patterns of amygdala growth in the first few years of life in children with ASD. These results suggest that the amygdala may be at the center of an abnormal brain network in ASD, and that amygdala pathology may vary across different groups in ASD. These findings also raise the possibility that the pattern of connectivity between the amygdala and other brain regions is altered in ASD. However, potential alterations in the white-matter pathways associated with the amygdala have not been thoroughly investigated. Diffusion tensor imaging (DTI) allows for in vivo visualization and investigation of pathways in the brain. DTI studies have already begun to identify white-matter abnormalities in the adult ASD brain, but no studies have investigated amygdala connectivity early in life when ASD symptoms first emerge and when abnormal amygdala enlargement is most pronounced. The proposed research will utilize DTI to investigate amygdala connectivity in a large longitudinal group of preschool-aged children with ASD and typically developing control children. By examining the integrity of connections to and from the amygdala in young children over several years, the proposed research will contribute significantly to our understanding of amygdala abnormalities in ASD. In addition, by examining white-matter pathways in a large group of extensively phenotyped children with ASD, this proposal seeks to further identify specific subtypes of neuropathology in ASD.