Autism spectrum disorder (ASD) is a developmental disorder that is characterized by difficulties with social interaction and interpersonal communication. It has been argued that abnormal attentional function to exogenous stimuli precedes and contributes to the core ASD symptoms. Notably, the locus ceruleus (LC) and its noradrenergic projections throughout the brain modulate attentional function, but the extent to which this locus ceruleus–norepinephrine (LC–NE) system influences attention in individuals with ASD, who frequently exhibit dysregulated alerting and attention orienting, is unknown. We examined dynamic attention control in girls and boys with ASD at rest using the pupil dilation response (PDR) as a noninvasive measure of LC–NE activity. When gender- and age-matched neurotypical participants were passively exposed to an auditory stream, their PDR decreased for recurrent stimuli but remained sensitive to surprising deviant stimuli. In contrast, children with ASD showed less habituation to recurrent stimuli as well as a diminished phasic response to deviants, particularly those containing social information. Their tonic habituation impairment predicts their phasic orienting impairment, and both impairments correlated with the severity of ASD symptom. Because of the fact that these pupil-linked responses are observed when individuals passively listen without any task engagement, our findings imply that the intricate and dynamic attention allocation mechanism, mediated by the subcortical LC–NE system, is impaired in ASD.

SIGNIFICANCE STATEMENT Autistic individuals show attentional abnormalities to even simple sensory inputs, which emerge even before formal diagnosis. One possible mechanism behind these abnormalities is a malfunctioning pacemaker of their attention system, the locus ceruleus–norepinephrine pathway. Here we found, according to the pupillary response (a noradrenergic activity proxy), autistic children are hypersensitive to repeated sounds but hyposensitive to surprising deviant sounds when compared with age-matched controls. Importantly, hypersensitivity to repetitions predicts hyposensitivity to deviant sounds, and both abnormalities positively correlate to the severity of autistic symptoms. This provides strong evidence that autistic children have faulty noradrenergic regulation, which might underly the attentional atypicalities previously evidenced in various cortical responses in autistic individuals.

自闭症谱系障碍（ASD）是一种发育障碍，其特征是社交互动和人际沟通困难。有人认为，对外源性刺激的异常注意功能先于并促成核心 ASD 症状。值得注意的是，蓝斑 (LC) 及其在整个大脑中的去甲肾上腺素能投射调节注意力功能，但这种蓝斑-去甲肾上腺素 (LC-NE) 系统影响 ASD 个体注意力的程度，他们经常表现出异常的警觉和注意力定向，未知。我们使用瞳孔扩张反应 (PDR) 作为 LC-NE 活动的非侵入性测量来检查患有 ASD 的女孩和男孩在休息时的动态注意力控制。当性别和年龄匹配的神经典型参与者被动地暴露在听觉流中时，他们的 PDR 因反复刺激而降低，但对令人惊讶的异常刺激仍然敏感。相比之下，患有 ASD 的儿童对反复性刺激的习惯较少，并且对异常的阶段性反应减弱，尤其是那些包含社会信息的异常。他们的强直习惯障碍预示着他们的阶段性定向障碍，这两种障碍都与 ASD 症状的严重程度相关。由于当个体在没有任何任务参与的情况下被动倾听时观察到这些与瞳孔相关的反应，我们的研究结果表明，由皮层下 LC-NE 系统介导的复杂和动态的注意力分配机制在 ASD 中受损。患有 ASD 的儿童对反复性刺激的习惯较少，并且对偏差的阶段性反应减弱，尤其是那些包含社会信息的偏差。他们的强直习惯障碍预示着他们的阶段性定向障碍，这两种障碍都与 ASD 症状的严重程度相关。由于当个体在没有任何任务参与的情况下被动倾听时观察到这些与瞳孔相关的反应，我们的研究结果表明，由皮层下 LC-NE 系统介导的复杂和动态的注意力分配机制在 ASD 中受损。患有 ASD 的儿童对反复性刺激的习惯较少，并且对偏差的阶段性反应减弱，尤其是那些包含社会信息的偏差。他们的强直习惯障碍预示着他们的阶段性定向障碍，这两种障碍都与 ASD 症状的严重程度相关。由于当个体在没有任何任务参与的情况下被动倾听时观察到这些与瞳孔相关的反应，我们的研究结果表明，由皮层下 LC-NE 系统介导的复杂和动态的注意力分配机制在 ASD 中受损。

重要性声明自闭症患者即使是简单的感觉输入也表现出注意力异常，这些输入甚至在正式诊断之前就出现了。这些异常背后的一个可能机制是他们的注意力系统的起搏器故障，即蓝斑-去甲肾上腺素通路。在这里，我们发现，根据瞳孔反应（去甲肾上腺素能活动代理），与年龄匹配的对照组相比，自闭症儿童对重复的声音过敏，但对令人惊讶的异常声音过敏。重要的是，对重复的超敏反应预示着对异常声音的超敏反应，并且这两种异常都与自闭症症状的严重程度呈正相关。这提供了强有力的证据表明自闭症儿童的去甲肾上腺素能调节有缺陷，