Sensory consequences of action in children with autism spectrum disorders

感觉和运动障碍是自闭症谱系障碍(ASD)的核心特征，并有助于 严重的功能障碍。在当前的应用程序中，我们假设更改之间的关系 在ASD的感觉和动作中，强调感觉运动环路在试图理解 损伤机制。特别是，据我们所知，我们首次预测， 动作和知觉之间的联系导致了自我产生的运动行为的不同知觉质量 ASD.我们提出了一系列翻译实验范式来检验这一新的假设。 所有可移动的生物体都配备了一种机制，用于减弱感官后果 自我生成的动作，允许增强对外部信息的处理。具体地说，是必然的排放 (CD)信号被发送到感觉脑区域，并代表发送到较低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，从而 感觉脑区可以减弱他们对自我启动行为的反应。在听觉领域，CD允许 对自身产生的声音(例如，语音)的感官反应减弱。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的特征是CD信号的干扰，从而使受影响的个体 经历对自己行为的反应增加，可能会导致对外部环境的反应不足 感官刺激和内心的专注。关键的是，这些假定的CD赤字后果是好的- 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的 源于动物神经生理学的行为范式，与眼球跟踪和 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 与配对良好的典型发展中的对照相比。我们假设在ASD中CD的干扰将 证据是：(1)听觉脑电反应对自身产生的声音的衰减减少；以及(2)改变 眼球跳动后的视觉感知和运动规划，与使用失败一致 CD来补偿这一运动。我们将探讨CD缺陷是否与临床特征有关，包括 不仅是感觉和运动症状，而且还有更高级别的社交和移情功能缺陷，这 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CD在ASD中的第一次调查。因此，这一创新的，翻译的- 扎根项目利用认知神经科学解决了ASD研究和知识中的一个关键差距 探索特定的、特征明确的大脑机制的技术，这可能是ASD核心特征的基础。我们的 这些发现有可能将ASD的核心特征与单个神经元的活动联系起来，提供了对 潜在的神经机制驱动ASD的症状，并可能为干预提供新的靶点。

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.