Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe-University, Deutschordenstraße 50, 60528, Frankfurt Am Main, Germany.
Centre for Brain and Cognitive Development, Birkbeck College, University of London, Malet Street, London, UK.
Mol Autism. 2023 Feb 9;14(1):5. doi: 10.1186/s13229-023-00537-6.
Attenuated social attention is a key marker of autism spectrum disorder (ASD). Recent neuroimaging findings also emphasize an altered processing of sensory salience in ASD. The locus coeruleus-norepinephrine system (LC-NE) has been established as a modulator of this sensory salience processing (SSP). We tested the hypothesis that altered LC-NE functioning contributes to different SSP and results in diverging social attention in ASD.
We analyzed the baseline eye-tracking data of the EU-AIMS Longitudinal European Autism Project (LEAP) for subgroups of autistic participants (n = 166, age = 6-30 years, IQ = 61-138, gender [female/male] = 41/125) or neurotypical development (TD; n = 166, age = 6-30 years, IQ = 63-138, gender [female/male] = 49/117) that were matched for demographic variables and data quality. Participants watched brief movie scenes (k = 85) depicting humans in social situations (human) or without humans (non-human). SSP was estimated by gazes on physical and motion salience and a corresponding pupillary response that indexes phasic activity of the LC-NE. Social attention is estimated by gazes on faces via manual areas of interest definition. SSP is compared between groups and related to social attention by linear mixed models that consider temporal dynamics within scenes. Models are controlled for comorbid psychopathology, gaze behavior, and luminance.
We found no group differences in gazes on salience, whereas pupillary responses were associated with altered gazes on physical and motion salience. In ASD compared to TD, we observed pupillary responses that were higher for non-human scenes and lower for human scenes. In ASD, we observed lower gazes on faces across the duration of the scenes. Crucially, this different social attention was influenced by gazes on physical salience and moderated by pupillary responses.
The naturalistic study design precluded experimental manipulations and stimulus control, while effect sizes were small to moderate. Covariate effects of age and IQ indicate that the findings differ between age and developmental subgroups.
Pupillary responses as a proxy of LC-NE phasic activity during visual attention are suggested to modulate sensory salience processing and contribute to attenuated social attention in ASD.
注意力减弱是自闭症谱系障碍（ASD）的一个关键标志物。最近的神经影像学研究结果也强调了 ASD 中感觉突显处理的改变。蓝斑-去甲肾上腺素系统（LC-NE）已被确定为这种感觉突显处理（SSP）的调节剂。我们测试了这样一个假设，即 LC-NE 功能的改变导致了不同的 SSP，并导致 ASD 中不同的社会注意力。
我们分析了欧盟自闭症纵向研究项目（LEAP）的基线眼动追踪数据，该研究包括自闭症参与者（n=166，年龄=6-30 岁，智商=61-138，性别[女性/男性]=41/125）或神经典型发育（TD；n=166，年龄=6-30 岁，智商=63-138，性别[女性/男性]=49/117）的亚组，这些亚组在人口统计学变量和数据质量方面是匹配的。参与者观看了 85 段简短的电影片段，描绘了人类在社交情境中的（人类）或没有人类的（非人类）场景。通过注视物理和运动突显物以及相应的瞳孔反应来估计 SSP，瞳孔反应反映了 LC-NE 的相位活动。通过手动定义感兴趣区域来估计社会注意力。通过线性混合模型比较组间差异，并考虑场景内的时间动态关系来将 SSP 与社会注意力相关联。模型考虑了共患精神病理学、注视行为和亮度。
我们没有发现组间在注视突显物上的差异，而瞳孔反应与注视物理和运动突显物有关。与 TD 相比，在 ASD 中，我们观察到非人类场景的瞳孔反应较高，而人类场景的瞳孔反应较低。在 ASD 中，我们观察到整个场景中对面孔的注视较低。至关重要的是，这种不同的社会注意力受到对物理突显物的注视的影响，并受到瞳孔反应的调节。
自然主义的研究设计排除了实验操作和刺激控制，而效应大小较小到中等。年龄和智商的协变量效应表明，这些发现在年龄和发育亚组之间有所不同。
作为视觉注意力期间 LC-NE 相位活动的代理，瞳孔反应被认为调节感觉突显处理，并导致 ASD 中社会注意力减弱。
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