Functional Neuroimaging of Attention in Autism

描述（由申请人提供）：对自闭症谱系障碍（ASD）的原因和治疗的研究受到儿童和成人在我们诊所的极端异质性的限制。注意力不集中和多动/冲动症状作为ASD异质性的一个促成因素越来越受到重视。我们的工作表明，这些症状的存在会导致更糟糕的结果（更多的适应不良行为和更差的日常生活技能）。临床医生已经调整了注意力缺陷/多动障碍（ADHD）的诊断和治疗，但这种方法显示哌甲酯的疗效降低（即，利他林）治疗ASD儿童。这表明ADHD症状的另一种病理生理学。这项拟议中的研究将使用功能性MRI和静息状态MRI沿着新的数据驱动方法来检查ASD和ADHD症状儿童的大脑网络中断。这种方法具有两个明显的优点：1）通过反应抑制挖掘的基底神经节-丘脑皮质回路是明确定义的，并且已知在患有原型ADHD的儿童中被破坏;以及2）我们的数据驱动的方法不对所识别的潜在亚组或大脑区域之间的连接性进行先验假设。我们将在8-10岁的ASD儿童（n=30）和典型发育对照组（n=15）中检查ADHD症状和日常环境中的抑制控制。这些儿童将完成功能磁共振成像和静息状态扫描，以检查功能神经解剖学和反应抑制的功能连接。我们假设，我们的数据驱动的方差方法将确定一种模式的儿童ASD和几个ADHD症状和两种模式的ASD亚组与显着的ADHD症状：一组功能磁共振成像反应抑制激活模式类似于典型的ADHD儿童，和一组模式不同于典型的ADHD。我们假设，在ASD组中，ADHD症状和日常抑制控制障碍减少时，参与反应抑制的网络之间的功能连接将具有更大的网络内相关性和更低的网络间相关性。如果成功，我们将确定新的基于生物学的亚组来表征ASD，以及确定可以在未来治疗试验中测试的ADHD症状的新治疗靶点。

DESCRIPTION (provided by applicant): Research into the causes and treatments of Autism Spectrum Disorders (ASD) are limited by extreme heterogeneity in how children and adults present at our clinics. There is an increasing appreciation for inattention and hyperactivity/impulsivity symptoms as a contributing factor to heterogeneity in ASD. Our work shows that the presence of these symptoms leads to worse outcomes (more maladaptive behaviors and poorer daily living skills). Clinicians have adapted diagnostics and treatments from Attention Deficit/Hyperactivity Disorder (ADHD), but this approach has shown reduced efficacy of methylphenidate (i.e., ritalin) treatment in children with ASD. This suggests an alternative pathophysiology for the ADHD symptoms. The proposed study will use functional MRI and rest state MRI along with novel, data-driven methods to examine brain networks disrupted in children with ASD and ADHD symptoms. This approach has two distinct advantages: 1) a basal ganglia-thalamocortical loop tapped by response inhibition is well- defined and known to be disrupted in children with prototypical ADHD; and 2) our data-driven methods make no a priori assumptions about potential sub-groups identified or connectivity among brain regions. We will examine the presence of ADHD symptoms and inhibitory control in everyday settings in 8-10-year-old children with ASD (n=30) and typically developing controls (n=15). These children will complete fMRI and resting state scans to examine functional neuroanatomy and functional connectivity of response inhibition. We hypothesize that our data-driven variance methods will identify one pattern of children with ASD and few ADHD symptoms and two patterns of ASD subgroups with significant ADHD symptoms: one group with fMRI response inhibition activation patterns similar to prototypical ADHD children, and one group with patterns distinct from prototypical ADHD. We hypothesize that functional connectivity among networks involved in response inhibition will have greater intra-network correlations and lower inter-network correlations as ADHD symptoms and everyday inhibitory control impairments decrease in the ASD group. If successful, we will identify novel biologically- based subgroups to characterize ASD, as well as identify novel treatment targets for ADHD symptoms that can be tested in future therapeutic trials.