Neural mechanisms of sensory over-responsivity in children with and without ASD

患有和不患有自闭症谱系障碍的儿童感觉过度反应的神经机制

• 批准号: 10705283
• 负责人: Rebecca Schwarzlose
• 金额: $ 13.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10705283
• 关键词: Affect; Anxiety; Anxiety Disorders; Area; Attenuated; Auditory; Auditory area; Award; Basic Science; Brain; Child; Childhood; Clinical; Committee Members; Communities; Data; Data Set; Development; Diagnosis; Distress; Etiology; Event; Exhibits; Family; Fright; Functional Magnetic Resonance Imaging; Future; Goals; Health; Impairment; Institution; Intervention; Knowledge; Learning; Location; Measurable; Measurement; Measures; Mental disorders; Mentors; Neurodevelopmental Disorder; Neurosciences Research; Noise; Pathway interactions; Personal Satisfaction; Phase; Prevalence; Psychopathology; Reaction; Research; Research Personnel; Rest; Risk; Running; Scanning; School-Age Population; Scientific Advances and Accomplishments; Scientist; Sensory; Signal Transduction; Site; Social isolation; Standardization; Stimulus; Symptoms; Tactile; Techniques; Testing; Training; Work; autism spectrum disorder; autistic children; base; career; complex data; cost; effective intervention; experience; functional MRI scan; functional disability; improved; innovation; insight; multilevel analysis; neural; neural correlate; neuroadaptation; neuromechanism; novel; novel strategies; nutrition; peer; poor sleep; recruit; response; sensory mechanism; sensory neuroscience; sensory stimulus; skills; social; success; tool; translational approach

PROJECT ABSTRACT Sensory over-responsivity (SOR), or strong negative reactions to and avoidance of innocuous sensory stimuli, affects about one in five school-age children and about two-thirds of children with autism spectrum disorder (ASD) and several other common neurodevelopmental disorders. Children with SOR experience considerable short- and long-term distress and impairment including fear and anxiety, poor sleep and nutrition, isolating social difficulties, and increased risk of mental illness. The cost of SOR in childhood is compounded by its disruption of developmentally appropriate social and situational experiences and its deleterious effects on family functioning. Despite its prevalence and impact on health and wellbeing, the causes of SOR are poorly understood and existing treatment approaches have met with limited success. Identifying the specific neural mechanisms that are disrupted in SOR could provide insights into its etiology and suggest promising approaches for developing effective interventions. Studies of typical sensory processing have revealed basic neural mechanisms that promote adaptive sensory responses, highlighting a powerful new translational approach to investigating the neural bases of SOR. The goal of this K99/R00 Pathway to Independence Award is to provide the applicant with the training needed to test if these neural mechanisms are disrupted in children with SOR and to support her continued success as an independent investigator. To achieve this goal, the applicant has assembled a committee of exceptional mentors and experts who will provide her with training in clinical presentations and assessments of ASD and SOR (Drs. Constantino, Sylvester, Green, and Pruett), administering functional MRI scans to children with and without ASD and SOR (Drs. Green, Sylvester, Dapretto, Pruett, and Dosenbach), applying multilevel models to complex datasets (Dr. Jackson), and developing skills for success as an independent investigator at a major research institution (all committee members). The proposed training will allow the applicant to test predictions about the relationship between one neural mechanism (suppression) and SOR in children using existing data and to pilot a functional MRI task to assess a second neural mechanism (surprise) in children during the K99 phase. Results from this work will inform the R00 phase, which will entail testing whether three neural mechanisms (adaptation, suppression, and surprise) are attenuated in sensory and fronto-limbic brain areas of children with SOR, both with and without ASD. This innovative research approach will clarify whether predictive mechanisms are disrupted in children with SOR and localize disruptions to specific brain areas, advancing scientific understanding of SOR and highlighting promising targets for interventions to be tested in a R01. Collectively, the proposed training and research will provide the applicant with the data, tools, and skills needed to launch a successful career at a top-tier research institution.

项目摘要 感觉过度反应（SOR），或对无害感觉刺激的强烈负面反应和回避， 大约五分之一的学龄儿童和大约三分之二的自闭症谱系障碍儿童受到影响 (ASD)和其他几种常见的神经发育障碍。患有SOR的儿童 短期和长期的痛苦和损害，包括恐惧和焦虑，睡眠和营养不良，孤立的社会 困难，并增加精神疾病的风险。儿童时期SOR的成本因其对儿童健康的破坏而加剧。 适合发展的社会和情境经验及其对家庭功能的有害影响。 尽管它的流行和对健康和福祉的影响，SOR的原因知之甚少， 现有的治疗方法取得的成功有限。识别特定的神经机制， 在SOR中被破坏可以提供对其病因学的见解，并提出有希望的方法， 有效干预。对典型感觉处理的研究揭示了基本的神经机制， 促进适应性感官反应，突出了一个强大的新的翻译方法来调查 SOR的神经基础这个K99/R 00独立之路奖的目标是为申请人提供 测试这些神经机制是否在SOR儿童中被破坏并支持她所需的训练 作为一名独立的调查员继续取得成功。为达致这个目标，申请人已 由杰出的导师和专家组成的委员会，他们将为她提供临床演示方面的培训， ASD和SOR评估（Constantino、西尔维斯特、绿色和Pruett博士），进行功能性MRI检查 对患有和不患有ASD和SOR的儿童进行扫描（绿色、西尔维斯特、Dapretto、Pruett和Dosenbach博士）， 将多层次模型应用于复杂数据集（杰克逊博士），并发展成功的技能， 主要研究机构的独立调查员（所有委员会成员）。拟议的培训将 允许申请人测试关于一种神经机制（抑制）与 使用现有数据在儿童中进行SOR，并引导功能性MRI任务以评估第二神经机制 K99阶段的儿童中。这项工作的结果将为R 00阶段提供信息， 测试三种神经机制（适应，抑制和惊喜）是否在感觉和 有或没有ASD的SOR儿童的额边缘脑区。这种创新的研究方法 将阐明是否预测机制被打乱，在儿童与SOR和本地化中断，以具体 大脑区域，推进对SOR的科学理解，并强调有希望的干预目标， 在R 01中测试。总的来说，拟议的培训和研究将为申请人提供数据、工具， 以及在顶级研究机构开展成功职业生涯所需的技能。