Illuminating brain function during imitation in children with ASD with DOT

项目摘要/摘要 这些研究的长期目标是推进高密度漫反射光学层析成像(HD-DOT)方法 用于评估患有自闭症谱系障碍(ASD)的学龄儿童的脑-行为关系 蹒跚学步的孩子在自然主义的环境中模仿新奇的粗大运动时，有患自闭症的风险。 我们提交这份申请是为了回应FOA：PA-21-200，自闭症谱系障碍研究。在……里面 典型的发展，模仿与几种对正常社会至关重要的行为的出现有关 互动和沟通，包括共同关注、游戏启动、社会联系和亲社会行为。 事实上，已经观察到模仿受损的模式，以及更普遍的视觉-运动整合(VMI)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中。开发模仿作为表型生物标记物的一个挑战是缺乏对神经的理解 ASD模仿缺陷的机制，以及神经影像文献中的变量结果。这个 混合的发现可能是由于在评估功能磁学中的运动模仿方面的显著限制 磁共振成像(FMRI)扫描环境，运动受到严格限制。这种脱节 自闭症儿童的一致行为差异与可变神经影像文献之间的关系 推动了当前的提议，在电机模拟过程中使用HD-DOT。HD-DOT提供了令人信服的 替代方案，克服了fMRI的显著人体工学限制，并通过 自然主义环境下的可穿戴帽子非常适合研究两所学校的粗大运动和模仿- 年长的儿童和蹒跚学步的儿童。拟议的研究计划具有高度的创新性、变革性，并具有 有可能阐明ASD的潜在机制，为临床干预提供信息，并改善预后。AS 因此，这项研究与NIMH的使命是一致的：转变对 通过基础和临床研究治疗精神疾病，为预防、康复和治愈铺平道路。早些时候 从18-48个月龄开始的行为和教育干预，改善了以下几个子集的结果 病人。神经成像方法已经显示出对ASD的神经特征的敏感性，这可能会提示 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来开辟新的道路 患有自闭症的学龄儿童和学龄前儿童的大脑功能直接影响运动。 具体地说，我们将测量神经信号，同时参与者进行自然运动模拟和 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，即影响社交沟通、接受和表达语言、运动协调 破坏，甚至限制和重复的行为。此外，这一战略提供了多样化的方法来 将适用于整个发展的评估，并可能有助于确定共同机制 自闭症的不同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.