Sensory consequences of action in children with autism spectrum disorders

自闭症谱系障碍儿童行动的感官后果

• 批准号: 9434242
• 负责人: Jennifer Foss-Feig
• 金额: $ 26.57万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-14 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9434242
• 关键词: 17 year old; Action Potentials; Address; Adolescent; Affect; Animals; Area; Attention; Attenuated; Auditory; Auditory Perception; Automobile Driving; Awareness; Basic Science; Behavior; Behavioral; Behavioral Paradigm; Biological; Brain; Brain region; Child; Clinical; Complex; Development; Developmental Process; Discrimination; Electrophysiology (science); Empathy; Esthesia; Etiology; Event; Event-Related Potentials; Eye; Eye Movements; Failure; Foundations; Impairment; Individual; Intervention; Investigation; Knowledge; Lead; Link; Literature; Methodology; Motor; Motor Pathways; Movement; Neurobiology; Neurologic; Neurons; Neuropsychology; Organism; Outcome Study; Perception; Procedures; Production; Psychophysics; Research; Retinal; Saccades; Sensory; Severities; Signal Transduction; Social Behavior; Social Functioning; Social Interaction; Specific qualifier value; Speech; Stimulus; Symptoms; Techniques; Technology; Testing; Time; Translating; Visual Perception; Visual system structure; Work; attenuation; autism spectrum disorder; cognitive neuroscience; disability; disorder control; experience; functional disability; high risk; innovation; insight; interest; motor deficit; motor symptom; multidisciplinary; neuromechanism; neurophysiology; neuropsychiatric symptom; neurotransmission; novel; oculomotor; relating to nervous system; repetitive behavior; response; sensory stimulus; sensory system; sex; social; sound

Sensory and motor deficits represent core features of autism spectrum disorder (ASD) and contribute to significant functional impairment. In the current application, we hypothesize a relationship between alterations in sensation and action in ASD, highlighting the importance of sensorimotor loops in attempting to understand mechanisms of impairment. In particular, we predict - to our knowledge, for the first time - that a breakdown in the link between action and perception leads to a different perceptual quality of self-generated motor acts in ASD. We propose a battery of translational experimental paradigms to test this novel hypothesis. All mobile organisms are equipped with a mechanism that serves to attenuate the sensory consequences of self-generated action, allowing enhanced processing of external information. Specifically, corollary discharge (CD) signals are sent to sensory brain areas and represent a copy of movement signals sent to lower motor regions. CD signals allow organisms to predict the sensory consequences of an imminent movement, such that sensory brain regions can attenuate their response to self-initiated action. In the auditory domain, CD allows dampening of the sensory response to self-generated sounds (e.g., speech). In the oculomotor domain, CD allows the visual system to prepare for change in retinal input following an eye movement. We propose that ASD is characterized by disturbances in CD signaling, such that affected individuals experience increased response to their own actions, potentially resulting in hypo-responsiveness to external sensory stimuli and internal preoccupation. Critically, these putative consequences of CD deficits are well- replicated ASD features, but CD itself has never been tested in ASD. Our approach is to capitalize on elegant behavioral paradigms derived from animal neurophysiology, in combination with eye tracking and electrophysiology (EEG), to evaluate the integrity of CD signals in children and adolescents with ASD, as compared to well-matched typically developing controls. We hypothesize that disturbances in CD in ASD will be evidenced in: (1) reduced attenuation of auditory EEG responses to self-generated sounds; and (2) altered visual perception and movement planning following a saccadic eye movement, consistent with a failure to use CD to compensate for this movement. We will explore whether CD deficits relate to clinical features, including not only sensory and motor symptoms, but also higher order deficits in social and empathic functioning, which could reflect downstream effects of basic sensorimotor alterations. To our knowledge, this study is the first investigation of CD in ASD. Thus, this innovative, translationally- grounded project addresses a key gap in ASD research and knowledge, using cognitive neuroscience techniques to probe a specific, well-characterized brain mechanism that may underlie core ASD features. Our findings have the potential to link core ASD features to activity of single neurons, providing unique insight into potential neural mechanisms driving symptoms in ASD and potentially offering novel targets for intervention.

感觉和运动缺陷代表了自闭症谱系障碍 (ASD) 的核心特征，并导致 显着的功能障碍。在当前的应用中，我们假设改变之间存在关系 在自闭症谱系障碍的感觉和行动中，强调了感觉运动回路在尝试理解的过程中的重要性 损伤机制。特别是，据我们所知，我们首次预测， 行动和感知之间的联系导致了自我产生的运动行为的不同感知质量 自闭症谱系障碍。我们提出了一系列转化实验范式来测试这一新假设。 所有移动生物体都配备了一种可以减弱感官后果的机制 自我生成的行动，允许增强对外部信息的处理。具体来说，伴随放电 (CD) 信号被发送到感觉脑区域并代表发送到下运动的运动信号的副本 地区。 CD 信号使生物体能够预测即将发生的运动的感官后果，例如 感觉脑区域可以减弱他们对自发行动的反应。在听觉领域，CD 允许 抑制对自身产生的声音（例如语音）的感官反应。在动眼神经领域，CD 允许视觉系统为眼球运动后视网膜输入的变化做好准备。 我们认为 ASD 的特点是 CD 信号传导紊乱，因此受影响的个体 对自己行为的反应增加，可能导致对外部反应低下 感官刺激和内在关注。至关重要的是，CD 赤字的这些假定后果是很好的—— 复制了 ASD 功能，但 CD 本身从未在 ASD 中进行过测试。我们的方法是利用优雅 源自动物神经生理学的行为范式，结合眼动追踪和 电生理学 (EEG)，评估患有 ASD 的儿童和青少年 CD 信号的完整性，如 与匹配良好的典型开发对照相比。我们假设自闭症谱系障碍 (ASD) 中的 CD 紊乱将 表现在：（1）听觉脑电图对自身产生的声音的反应衰减减少； (2) 改变 眼球扫视运动后的视觉感知和运动计划，与使用失败一致 CD 来补偿这种运动。我们将探讨 CD 缺陷是否与临床特征相关，包括 不仅是感觉和运动症状，还有社交和共情功能的高阶缺陷， 可以反映基本感觉运动改变的下游影响。 据我们所知，这项研究是自闭症谱系障碍中 CD 的首次研究。因此，这种创新的、转化的—— 扎根项目利用认知神经科学解决自闭症谱系障碍研究和知识的关键差距 技术来探测可能构成自闭症谱系障碍核心特征的特定的、充分表征的大脑机制。我们的 研究结果有可能将自闭症谱系障碍的核心特征与单个神经元的活动联系起来，从而提供独特的见解 驱动自闭症谱系障碍症状的潜在神经机制，并可能提供新的干预目标。