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），或对无害的感觉刺激产生强烈的负面反应和回避， 影响约五分之一的学龄儿童和约三分之二的自闭症谱系障碍儿童 （自闭症谱系障碍）和其他几种常见的神经发育障碍。患有 SOR 的儿童经历相当多 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、孤立社交 困难，并增加患精神疾病的风险。儿童期 SOR 的成本因它对 适合发展的社会和情境经历及其对家庭功能的有害影响。 尽管 SOR 很普遍并且对健康和福祉有影响，但人们对 SOR 的原因知之甚少，并且 现有的治疗方法取得的成功有限。确定具体的神经机制 SOR 中的干扰可以提供对其病因学的见解，并提出有希望的开发方法 有效的干预措施。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，强调一种强大的新转化方法来研究 SOR 的神经基础。 K99/R00 独立之路奖的目标是为申请人提供 测试 SOR 儿童的这些神经机制是否受到干扰并为她提供支持所需的培训 作为独立调查员继续取得成功。为了实现这一目标，申请人组建了一个 由杰出导师和专家组成的委员会将为她提供临床演示和培训 ASD 和 SOR 评估（Constantino、Sylvester、Green 和 Pruett 博士），进行功能性 MRI 对患有或不患有 ASD 和 SOR 的儿童进行扫描（Green、Sylvester、Dapretto、Pruett 和 Dosenbach 博士）， 将多级模型应用于复杂的数据集（杰克逊博士），并培养成功的技能 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 允许申请人测试对一种神经机制（抑制）和 儿童中的 SOR 使用现有数据并试点功能性 MRI 任务来评估第二种神经机制 （惊喜）K99 阶段的儿童。这项工作的结果将为 R00 阶段提供信息，这将需要 测试三种神经机制（适应、抑制和惊喜）在感觉和认知方面是否减弱 患有 SOR 的儿童（无论是否患有自闭症谱系障碍）的额叶边缘大脑区域。这种创新的研究方法 将阐明患有 SOR 的儿童的预测机制是否受到干扰，并将干扰定位到特定的区域 脑区域，促进对 SOR 的科学理解，并强调有希望的干预目标 在 R01 中进行测试。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启成功职业生涯所需的技能。