Illuminating brain function during imitation in children with ASD with DOT

项目总结/摘要 这些研究的长期目标是推进高密度扩散光学层析成像（HD-DOT）方法 用于评估患有自闭症谱系障碍（ASD）的学龄儿童的大脑行为关系， 在自然环境中模仿新奇的粗大运动动作时，有发展ASD风险的幼儿。 我们提交此申请是为了回应FOA：PA-21-200，自闭症谱系障碍研究。在 在典型的发展过程中，模仿与一些对正常社会至关重要的行为的出现有关 互动和沟通，包括共同注意，游戏启动，社会联系，亲社会行为。 事实上，人们已经观察到了模仿和视觉-运动整合（VMI）受损的模式 在广泛的自闭症儿童中，模仿能力与社交能力有关。 在ASD发展模仿作为表型生物标志物的一个挑战是缺乏对神经系统的理解。 导致ASD中模仿缺陷的机制，以及神经影像学文献中的可变结果。的 混合的结果可能是由于在评估运动模仿的功能磁共振成像的显着局限性， 共振成像（fMRI）扫描环境，其中存在对运动的严格限制。这种脱节 ASD儿童一致的行为差异与可变的神经影像学文献之间 促使目前的建议，而不是使用HD-DOT在运动模仿。HD-DOT提供了一个引人注目的 一种替代方案，克服了功能性磁共振成像的重大人体工程学限制，并无声地成像大脑功能， 可穿戴的帽子在自然的设置理想的研究大运动和模仿在学校- 老年儿童和幼儿。拟议的研究计划是高度创新的，变革性的，并具有 有可能阐明潜在的机制，为临床干预提供信息，并改善ASD的结局。作为 因此，这项研究与NIMH的使命是和谐的：改变对疾病的理解和治疗。 通过基础和临床研究，为预防、康复和治疗精神疾病铺平道路。早期 从18-48个月开始的行为和教育干预，改善了以下儿童的结局： 患者神经影像学方法已经证明对ASD的神经特征的敏感性， 诊断和跟踪对干预措施的反应。在这里，我们建议通过双臂研究开辟新的道路， 大脑功能直接影响学龄和学龄前ASD儿童的运动。 具体来说，我们将在参与者进行自然运动模仿时测量神经信号， 运动观察这些数据可以为观察到的受损行为的特定方面提供标记 在ASD中，即受影响的社会沟通，接受和表达语言，运动协调 中断，甚至限制和重复的行为。此外，这一战略提供了一种多样化的办法， 评估将适用于整个发展过程，并可能有助于确定共同机制 不同的自闭症遗传途径导致了广泛的自闭症表型。

Project Summary / Abstract The long-term goal of these studies is to advance high-density diffuse optical tomography (HD-DOT) methods for evaluating brain-behavior relationships in school-aged children with autism spectrum disorder (ASD) and toddlers at risk for developing ASD while they imitate novel gross motor movements within a naturalistic setting. We are submitting this application in response to FOA: PA-21-200, Research on Autism Spectrum Disorders. In typical development, imitation is associated with the emergence of several behaviors crucial to normal social interaction and communication, including joint attention, play initiation, social affiliation, and prosocial behaviors. Indeed, patterns of impaired imitation, and visual-motor integration (VMI) more generally, have been observed across a wide range of children with ASD, with imitation ability being associated with social-communicative skills in ASD. A challenge in developing imitation as a phenotypic biomarker is the lack of understanding of the neural mechanisms contributing to imitation deficits in ASD, and the variable results in the neuroimaging literature. The mixed findings may be due to the significant limitations in assessing motor imitation in the functional magnetic resonance imaging (fMRI) scanning environment where there are severe restrictions on motion. This disconnect between consistent behavioral differences in children with ASD and the variable neuroimaging literature motivated the current proposal to use instead HD-DOT during motor imitation. HD-DOT provides a compelling alternative that overcomes the significant ergonomic limitations of fMRI and silently images brain function with a wearable cap in a naturalistic setting ideal for studies on gross motor movement and imitation in both school- aged children and toddlers. The proposed program of research is highly innovative, transformative, and has the potential to elucidate underlying mechanisms, inform clinical interventions, and improve outcome of ASD. As such, this research is harmonious with the mission of NIMH: to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. Early behavioral and educational interventions, starting at 18-48 months of age, improve outcomes in a subset of patients. Neuroimaging methods have demonstrated sensitivity to neural signatures of ASD that may inform diagnosis and track responses to interventions. Here we propose to forge new paths with a dual-armed study of brain function directly underlying motor movement in school- and pre-school-aged children with ASD. Specifically, we will measure neural signatures while participants perform naturalistic motor imitation and movement observation. These data may provide markers to the specific aspects of impaired behavior observed in ASD, namely affected social communication, receptive and expressive language, motor coordination disruption, and even restricted and repetitive behaviors. Further, this strategy provides a diversified approach to assessment that will be applicable across development, and may facilitate identification of common mechanisms by which disparate genetic pathways to autism result in the broad autistic phenotype.