Mapping Thalamocortical Networks Across Development in ASD

描述（由申请人提供）：自闭症谱系障碍（ASD）是一组广泛性发育障碍，其特征是社会互动和沟通缺陷，以及刻板或刻板的行为。这些复杂的行为问题部分源于更基本的感觉和运动系统的缺陷。丘脑在处理感觉信息和调节整体皮层活动方面起着核心作用。因此，丘脑功能障碍及其与皮层的连接可能是ASD的一些症状的原因。事实上，越来越多的证据表明，在自闭症谱系障碍患者中，丘脑的结构和功能是异常的，并导致了自闭症谱系障碍的症状。尽管有新的证据表明ASD中丘脑异常，但我们对ASD中丘脑病理的认识仍然存在一些关键空白。首先，丘脑皮质网络在地形上的组织使得单独的丘脑核投射到特定的皮质区域，这提高了丘脑皮质网络可能选择性地影响ASD的可能性。其次，我们对自闭症患者丘脑皮质网络的产后发育轨迹几乎一无所知。这一点至关重要，因为越来越多的证据表明，大脑的发育轨迹在ASD中发生了改变。此外，ASD症状的严重程度在整个生命周期中有所不同。因此，要全面了解ASD的丘脑回路以及丘脑皮质网络紊乱与ASD表型之间的关系，就需要对整个生命周期的丘脑皮质网络进行系统的绘制。这项提案将着手解决这些关键的差距。使用一种创新的静息状态fMRI方法，我们将确定丘脑皮质网络是否在ASD中发生改变（Aim 1）；研究自闭症患者丘脑皮质网络的发育轨迹（目的2）；并建立丘脑皮质网络与ASD症状表达的功能相关性（目的3）。这项工作将有助于我们对ASD的脑基础的理解。

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) are a group of pervasive developmental disorders characterized by deficits in social interaction and communication, and rigid or stereotypical behaviors. These complex behavioral problems arise, in part, from deficits in more basic sensory and motor systems. The thalamus plays a central role in processing sensory information and modulating overall cortical activity. Consequently, dysfunction of the thalamus and its connections with the cortex may account for some of the symptoms of ASD. Indeed, there is growing evidence that the structure and function of the thalamus is abnormal in ASD and contributes to ASD symptoms. Despite emerging evidence of thalamic abnormalities in ASD, several critical gaps in our knowledge about thalamic pathology in ASD remain. First, thalamocortical networks are organized topographically such that separate thalamic nuclei project to specific cortical areas raising the distinct possibility that thalamocortical networks may selectively affected in ASD. Second, we know virtually nothing about the post-natal developmental trajectories of thalamocortical networks in ASD. This is critical given mounting evidence that the developmental trajectories of the brain are altered in ASD. Moreover, the severity of ASD symptoms varies across the lifespan. Consequently, a complete understanding of thalamic circuitry in ASD and the relationship between thalamocortical network disturbances and ASD phenotypes will require systematic mapping of thalamocortical networks across the lifespan. This proposal will begin to address these critical gaps. Using an innovative resting-state fMRI method, we will determine if thalamocortical networks are altered in ASD (Aim 1); examine the developmental trajectories of thalamocortical networks in ASD (Aim 2); and establish the functional relevance of thalamocortical networks to the expression of ASD symptoms (Aim 3). The proposed work will contribute to our understanding of brain-basis of ASD.