Neural mechanisms of sensory reactivity and regulation in autism across development

自闭症跨发育过程中感觉反应和调节的神经机制

• 批准号: 10378475
• 负责人: Shulamite Abra Green
• 金额: $ 68.79万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10378475
• 关键词: Adolescence; Adult; Age; Amygdaloid structure; Arousal; Attention; Attenuated; Behavioral; Biological; Brain; Brain region; Child; Childhood; Clinical; Communities; Coping Skills; Cues; Data; Development; Developmental Course; Developmental Delay Disorders; Diagnostic; Emotional; Emotions; Foundations; Functional Magnetic Resonance Imaging; Goals; Impairment; Individual; Individual Differences; Intervention; Knowledge; Life; Loudness; Methods; Neurodevelopmental Disorder; Noise; Positioning Attribute; Prefrontal Cortex; Regulation; Sampling; Schools; Sensory; Severities; Spectrum Analysis; Stimulus; Testing; Thalamic structure; Touch sensation; Translating; Translations; Work; Youth; adolescent with autism spectrum disorder; autism spectrum disorder; autistic children; base; behavior measurement; design; developmental disease; emotion regulation; follow-up; gamma-Aminobutyric Acid; habituation; imaging study; improved; individuals with autism spectrum disorder; knowledge of results; longitudinal analysis; longitudinal design; neurobiological mechanism; neuromechanism; neuroregulation; personalized intervention; psychopharmacologic; relating to nervous system; resilience; response; sensory cortex; sensory gating; sensory mechanism; sensory stimulus; social; therapy design

PROJECT SUMMARY/ABSTRACT Sensory over-responsivity (SOR) is an impairing condition manifested as extreme sensitivity to stimuli such as loud noises or being touched. SOR is present across neurodevelopmental disorders, but is particularly prevalent in youth with autism spectrum disorders (ASD) with rates of at least 56-70%. SOR is a fundamental limitation to individuals’ ability to participate in the community, succeed in school, complete daily living tasks, and interact socially. Despite this, there are almost no empirically-based treatments for SOR, in part due to the lack of understanding of its underlying biological mechanisms. Furthermore, while SOR tends to decline across adolescence into adulthood, there is little understanding as to why and for whom it improves. Thus, the primary goals of this study are to identify the developmental course of SOR as well as neurobiological mechanisms through which it can be attenuated, both essential to developing interventions. Our team has conducted some of the first studies identifying key neural mechanisms of SOR across youth with ASD, including 1) over-reactive brain responses/reduced habituation in primary sensory cortices and amygdala, 2) reduced thalamic GABA, and 3) reduced prefrontal cortex (PFC)-amygdala functional connectivity during aversive sensory stimulation. Our prior studies also indicate that the subset of youth with ASD but low SOR show heightened amygdala-prefrontal connectivity during sensory stimulation, suggesting a mechanism for resilience against SOR. Our preliminary data also suggest that amygdala reactivity to aversive sensory stimulation declines with age while PFC activation increases. This proposal seeks to build on this foundation by examining biological mechanisms through which SOR may be attenuated either through natural development or through direct intervention, with the goal of proximate translation to treatment. Using a combined cross-sectional and longitudinal design, we will examine: 1) developmental changes in sensory reactivity in ASD compared to typically developing (TD) children; 2) developmental changes in two candidate neural mechanisms of sensory regulation (thalamic GABA and PFC- amygdala connectivity), and 3) the relative ability of two different emotion regulation strategies (attention cuing vs. reappraisal) in engaging sensory regulation. Based on our prior studies and preliminary data, we expect to see that behavioral and neural markers of SOR decrease with age, but that this decline happens later than is typical for youth with ASD, indicating a developmental delay in sensory regulation. We further expect that of our two candidate top-down mechanisms of sensory regulation that prefrontal-amygdala connectivity but not thalamic GABA will improve with development, which will inform our understanding of why SOR decreases with age and how best to treat it at different stages of development. Finally, we will compare the relative ability of attention cuing vs. reappraisal to engage PFC for youth of different ages and SOR severity. Results will directly inform both behavioral and psychopharmacological personalized interventions for SOR.

项目摘要/摘要 感官过度反应性（SOR）是一种表现为刺激的极端灵敏度的损害 例如大声的噪音或被触摸。 SOR存在于神经发育障碍中，但尤其是 在自闭症谱系障碍（ASD）的年轻人中普遍存在，比率至少为56-70％。 SOR是一个基本 限制个人参与社区，在学校成功，完成日常生活的能力以及 社交互动。尽管如此，几乎没有基于经验的SOR治疗方法，部分原因是缺乏 了解其潜在的生物学机制。此外，SOR倾向于遍布 青少年进入成年，几乎没有关于为什么和为谁改善的理解。那，主要 这项研究的目标是确定SOR的发育过程以及神经生物学机制 通过它可以减弱，这对于制定干预措施至关重要。我们的团队进行了一些 在识别ASD青年中SOR的关键神经机制的第一批研究中，包括1）过度反应性 脑反应/降低原发性皮质和杏仁核的习惯，2）丘脑GABA和 3）在厌恶感觉刺激期间，降低前额叶皮层（PFC）-Amygdala功能连通性。我们的 先前的研究还表明，ASD但SOR低的青年子集显示出杏仁核的增强 感觉刺激过程中的连通性，提出了一种针对SOR的弹性机制。我们的初步 数据还表明，杏仁核对厌恶感刺激的反应性随着年龄的增长而下降，而PFC激活 增加。该建议旨在通过研究生物学机制来建立基础 可以通过自然发展或直接干预来减弱SOR，目的是 接近治疗的近端翻译。使用横截面和纵向设计组合，我们将研究： 1）与通常发育（TD）儿童相比，ASD的感觉反应性的发展变化； 2） 感觉调节的两种候选神经力学的发展变化（丘脑GABA和PFC- 杏仁核连通性）和3）两种不同情绪调节策略的相对能力（注意提示 与重新评估的感官调节。根据我们先前的研究和初步数据，我们希望 看到SOR的行为和神经标记随着年龄的增长而减少，但是这种下降的发生时间比IS晚了 对于ASD的年轻人来说，典型的是感觉调节的发展延迟。我们进一步期望我们 前额叶 - 杏仁核连接性的两种候选自上而下的感觉调节机制，但不是 Thalamic Gaba将随着发展而改善 年龄以及如何在不同发展阶段最好地对待它。最后，我们将比较 注意提示与重新评估，以使PFC适合不同年龄和SOR严重性的年轻人。结果将直接 为SOR提供行为和心理药理个性化干预措施。