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，其特征是社交和沟通障碍，以及刻板或刻板的行为。这些复杂的行为问题部分是由更基本的感觉和运动系统的缺陷引起的。丘脑在处理感觉信息和调节整个皮层活动中起着核心作用。因此，丘脑及其与皮质的连接功能障碍可能导致ASD的一些症状。事实上，越来越多的证据表明，ASD患者丘脑的结构和功能异常，并导致ASD症状。 尽管出现了ASD丘脑异常的证据，但我们对ASD丘脑病理学的认识仍存在一些关键空白。首先，丘脑皮质网络组织拓扑结构，使单独的丘脑核项目的特定皮质区提出了不同的可能性，丘脑皮质网络可能选择性地影响ASD。其次，我们对ASD患者的丘脑皮质网络的出生后发育轨迹几乎一无所知。这是至关重要的，因为越来越多的证据表明，大脑的发育轨迹在ASD中被改变。此外，ASD症状的严重程度在整个生命周期中有所不同。因此，全面了解ASD中的丘脑回路以及丘脑皮质网络干扰与ASD表型之间的关系，将需要在整个生命周期中系统地绘制丘脑皮质网络。 本提案将开始解决这些关键差距。使用一种创新的静息态功能磁共振成像方法，我们将确定是否丘脑皮质网络在ASD中改变（目标1）;检查ASD中丘脑皮质网络的发育轨迹（目标2）;并建立丘脑皮质网络与ASD症状表达的功能相关性（目标3）。这些工作将有助于我们对ASD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.