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自闭症谱系障碍（ASD）的核心特征，并有助于 重大功能障碍。在当前的应用程序中，我们假设更改之间的关系 在ASD中的感觉和动作中，强调了感觉运动循环的重要性 损害机制。特别是，我们第一次预测 - 就我们的知识而言， 动作与感知之间的联系导致自我生成的运动的不同感知质量。 ASD。我们提出了一系列翻译实验范式来检验这一新假设。 所有移动生物都配备了一种机制，该机制可减轻感官后果 自我生成的动作，允许增强外部信息的处理。具体而言，推论排放 （CD）信号发送到感觉大脑区域，并表示发送到较低电机的运动信号的副本 地区。 CD信号允许生物体预测迫在眉睫的运动的感觉后果，以便 感官大脑区域可以减弱他们对自发行动的反应。在听觉域中，CD允许 对自我生成的声音的感觉反应减弱（例如，语音）。在动眼域中CD 允许视觉系统为眼睛运动后的视网膜输入变化做准备。 我们建议ASD的特征是CD信号传导中的干扰，从而影响了个体 经历对自己的行动的反应增加，可能导致对外部的反应 感官刺激和内部关注。至关重要的是，CD缺陷的这些假定后果是很好的 复制的ASD功能，但是CD本身从未在ASD中进行测试。我们的方法是利用优雅 源自动物神经生理学的行为范例，结合眼睛跟踪和 电生理学（EEG），以评估患有ASD的儿童和青少年CD信号的完整性 与匹配良好的通常开发控件相比。我们假设ASD中CD中的干扰将 可以证明：（1）听觉脑电图对自我生成的声音的响应减少； （2）改变 眼睛运动后的视觉感知和运动计划，与未能使用 CD弥补这一运动。我们将探讨CD缺陷是否与临床特征有关，包括 不仅有感觉和运动症状，而且在社会和移情功能中的高阶缺陷 可以反映基本感觉运动改变的下游效应。 据我们所知，这项研究是对ASD中CD的首次研究。因此，这种创新的，翻译的 - 接地项目解决了使用认知神经科学的ASD研究和知识的关键差距 探测特定，良好的大脑机制的技术，该机制可能是核心ASD特征的基础。我们的 发现有可能将核心ASD特征与单个神经元的活动联系起来，从而提供了独特的见解 潜在的神经机制驱动ASD中的症状，并可能为干预提供新的目标。