Mapping Thalamocortical Networks Across Development in ASD

描述(由申请人提供)：自闭症谱系障碍(ASD)是一组普遍存在的发育障碍，其特征是社交和沟通障碍，以及僵化或刻板的行为。这些复杂的行为问题在一定程度上是由更基本的感觉和运动系统缺陷引起的。丘脑在处理感觉信息和调节整体皮质活动方面起着核心作用。因此，丘脑功能障碍及其与皮质的联系可能是ASD的一些症状。事实上，越来越多的证据表明，自闭症患者丘脑的结构和功能异常，并导致自闭症症状。尽管出现了ASD丘脑异常的证据，但我们对ASD丘脑病理的认识仍然存在一些关键的空白。首先，丘脑皮质网络在地形图上被组织起来，使得分离的丘脑核团投射到特定的皮质区域，增加了丘脑皮质网络可能选择性地影响ASD的明显可能性。其次，我们对自闭症患者丘脑皮质网络的出生后发育轨迹几乎一无所知。鉴于越来越多的证据表明，自闭症患者大脑的发育轨迹发生了变化，这一点至关重要。此外，ASD症状的严重程度因寿命而异。因此，要完全了解ASD中的丘脑回路以及丘脑皮质网络障碍与ASD表型之间的关系，将需要系统地绘制整个寿命范围内的丘脑皮质网络图。这项提议将开始解决这些关键差距。使用一种创新的静息功能磁共振方法，我们将确定自闭症患者丘脑皮质网络是否发生改变(目标1)；检查自闭症患者丘脑皮质网络的发育轨迹(目标2)；并建立丘脑皮质网络与自闭症症状表达的功能相关性(目标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.