Department of Psychology, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213
Neuroscience Institute, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213.
J Neurosci. 2020 May 6;40(19):3815-3826. doi: 10.1523/JNEUROSCI.2680-19.2020. Epub 2020 Apr 6.
Autism spectrum disorder (ASD) is characterized partly by atypical attentional engagement, reflected in exaggerated and variable responses to sensory stimuli. Attentional engagement is known to be regulated by the locus ceruleus (LC). Moderate baseline LC activity globally dampens neural responsivity and is associated with adaptive deployment and narrowing of attention to task-relevant stimuli. In contrast, increased baseline LC activity enhances neural responsivity across cortex and widening of attention to environmental stimuli regardless of their task relevance. Given attentional atypicalities in ASD, this study is the first to evaluate whether, under different attentional task demands, individuals with ASD exhibit a different profile of LC activity compared with typically developing controls. Males and females with ASD and age- and gender-matched controls participated in a one-back letter detection test while task-evoked pupillary responses, an established correlate for LC activity, were recorded. Participants completed this task in two conditions, either in the absence or presence of distractor auditory tones. Compared with controls, individuals with ASD evinced atypical pupillary responses in the presence versus absence of distractors. Notably, this atypical pupillary profile was evident despite the fact that both groups exhibited equivalent task performance. Moreover, between-group differences in pupillary responses were observed specifically in response to task-relevant events, providing confirmation that the group differences most likely were specifically associated with distinctions in LC activity. These findings suggest that individuals with ASD show atypical modulation of LC activity with changes in attentional demands, offering a possible mechanistic and neurobiological account for attentional atypicalities in ASD. Individuals with autism spectrum disorder (ASD) exhibit atypical attentional behaviors, including altered sensory responses and atypical fixedness, but the neural mechanism underlying these behaviors remains elusive. One candidate mechanism is atypical locus ceruleus (LC) activity, as the LC plays a critical role in attentional modulation. Specifically, LC activity is involved in regulating the trade-off between environmental exploration and focused attention. This study shows that, under tightly controlled conditions, task-evoked pupil responses, an LC activity proxy, are lower in individuals with ASD than in controls, but only in the presence of task-irrelevant stimuli. This suggests that individuals with ASD evince atypical modulation of LC activity in accordance with changes in attentional demands, offering a mechanistic account for attentional atypicalities in ASD.
自闭症谱系障碍 (ASD) 的特征部分是注意力参与不典型，表现在对感觉刺激的反应夸大且多变。已知注意力参与受蓝斑核 (LC) 调节。LC 的基线活动适度抑制神经反应性，与注意力自适应分配和集中于与任务相关的刺激有关。相反，LC 基线活动增加会增强整个大脑皮层的神经反应性，并扩大对环境刺激的注意力，而不管这些刺激与任务的相关性如何。鉴于 ASD 中的注意力异常，这项研究首次评估了 ASD 个体在不同注意力任务需求下，是否表现出与对照组不同的 LC 活动模式。ASD 男性和女性以及年龄和性别匹配的对照组参与者参与了一项一背字母检测测试，同时记录了作为 LC 活动的既定相关物的瞳孔反应。参与者在两种条件下完成此任务，一种是在没有分心听觉声音的情况下，另一种是在存在分心听觉声音的情况下。与对照组相比，ASD 个体在存在和不存在分心物的情况下表现出异常的瞳孔反应。值得注意的是，尽管两组的任务表现相当，但仍存在这种非典型的瞳孔模式。此外，在对与任务相关的事件做出反应时观察到了组间瞳孔反应的差异，这证实了组间差异很可能与 LC 活动的差异特异性相关。这些发现表明，ASD 个体在注意力需求变化时表现出 LC 活动的异常调节，为 ASD 中的注意力异常提供了一种可能的机制和神经生物学解释。自闭症谱系障碍（ASD）患者表现出异常的注意力行为，包括改变的感觉反应和异常的固定性，但这些行为的神经机制仍不清楚。一个候选机制是异常的蓝斑核（LC）活动，因为 LC 在注意力调节中起着关键作用。具体来说，LC 活动涉及调节环境探索与集中注意力之间的权衡。这项研究表明，在严格控制的条件下，与 LC 活动相关的任务诱发的瞳孔反应在 ASD 个体中低于对照组，但仅在存在与任务无关的刺激时才会出现这种情况。这表明，ASD 个体表现出 LC 活动的异常调节，以适应注意力需求的变化，为 ASD 中的注意力异常提供了一种机制解释。
