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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要感觉过度反应 (SOR) 是一种损害状况，表现为对刺激极度敏感例如大声喧哗或被触摸，SOR 存在于神经发育障碍中，但尤为严重。患有自闭症谱系障碍 (ASD) 的青少年中普遍存在，SOR 率至少为 56-70%。个人参与社区、在学校取得成功、完成日常生活任务的能力受到限制，以及尽管如此，SOR 几乎没有基于经验的治疗方法，部分原因是缺乏。此外，SOR 往往会下降。从青春期到成年，人们很少了解它为何以及为谁而改善，因此，这是首要的。本研究的目标是确定 SOR 的发展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。的首批研究确定了自闭症谱系障碍 (ASD) 青少年 SOR 的关键神经机制，包括 1) 过度反应大脑反应/初级感觉皮层和杏仁核的习惯减少，2) 丘脑 GABA 减少，以及 3）在厌恶性感觉刺激期间前额皮质（PFC）-杏仁核功能连接减少。先前的研究还表明，患有自闭症谱系障碍 (ASD) 但 SOR 较低的青少年子集显示出内裤杏仁核-前额叶感觉刺激期间的连通性，表明我们初步的抵抗 SOR 的机制。数据还表明，杏仁核对厌恶性感觉刺激的反应性随着年龄的增长而下降，而 PFC 激活该提案旨在通过研究生物机制来建立这一基础。 SOR 可以通过自然发展或直接干预来减弱，目的是使用横截面和纵向相结合的设计，我们将检查： 1) 与典型发育 (TD) 儿童相比，自闭症谱系障碍 (ASD) 感觉反应性的发育变化；感觉调节的两种候选神经机制（丘脑 GABA 和 PFC-）的发育变化杏仁核连接），3）两种不同情绪调节策略的相对能力（注意提示根据我们之前的研究和初步数据，我们预计：看到 SOR 的行为和神经标志物随着年龄的增长而下降，但这种下降发生得晚于实际年龄这是患有自闭症谱系障碍 (ASD) 青少年的典型症状，表明我们的感觉调节发育迟缓。两个候选者自上而下的感觉调节机制，前额-杏仁核连接，但不是丘脑 GABA 会随着发育而改善，这将帮助我们理解为什么 SOR 随着发育而降低最后，我们将比较不同发育阶段的相对能力。不同年龄和 SOR 严重程度的青少年参与 PFC 的注意提示与重新评估结果将直接相关。为 SOR 的行为和心理药理学个性化干预提供信息。