Bast Nico, Ahmad Jumana, Mason Luke, Jones Emily J H, Matyjek Magdalena, Polzer Leonie, Luckhardt Christina, Müller Anna Katharina, McAlonan Grainne M, Banaschewski Tobias, Baumeister Sarah, Loth Eva, Freitag Christine M
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.
School of Human Sciences, University of Greenwich, London, UK.
Mol Autism. 2025 Aug 21;16(1):41. doi: 10.1186/s13229-025-00678-w.
Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing.
Autistic (n = 139) and non-autistic (n = 98) individuals were assessed during a passive auditory oddball task with pupillometry and electroencephalography. For every trial, a baseline pupil size (BPS) assessed LC-NE tonic activity that coincides with current arousal, while a stimulus-evoked pupillary response (SEPR) assessed LC-NE phasic activity that estimated sensory selectivity. Electroencephalography assessed amplitudes of mismatch negativity (MMN-amp) that estimated pre-attentive change detection as a brain-activity readout of sensory selectivity. Measures were modeled between groups within the task by combining Frequentist and Bayesian approaches.
Across groups, higher BPS was associated with more negative MMN-amp to standards and oddballs. A more negative MMN-amp to standards was associated with a higher SEPR to standards. Controlling for these associations, autistic versus non-autistic individuals showed a higher SEPR in response to standards. In addition, a positive association of BPS and SEPR to standards was specific to autistic individuals. With task progression, autistic versus non-autistic individuals showed a higher initial increase and subsequently steeper decrease of BPS. This was supported by Bayesian posterior distribution estimates.
A short trial duration required concatenating trials to epochs and applying a linear-time invariant filter to capture the slow pupil changes. Without an LC-NE manipulation, we cannot rule out that pupil changes are evoked by other cortical pathways than the LC-NE.
Across groups, LC-NE tonic upregulation is emphasized as a general mechanism that un-specifically increases pre-attentive change detection to all sensory stimuli, which then increases sensory selectivity to frequent stimuli. In autistic individuals, different sensory processing is characterized by increased sensory selectivity to frequent stimuli. This is likely caused by an LC-NE tonic upregulation. It associates autistic sensory processing with increased arousal upregulation that increases sensory selectivity to inconspicuous auditory information.
感觉处理需要对显著的感觉输入具有选择性。许多自闭症个体报告有不同的感觉处理方式，这与感觉选择性的改变有关。蓝斑去甲肾上腺素（LC-NE）系统调节感觉输入的神经元增益，这代表了感觉选择性的一种神经生理机制。在自闭症个体中，我们假设LC-NE张力上调会降低感觉选择性，并构成不同感觉处理方式的基础。
在一项被动听觉oddball任务中，使用瞳孔测量法和脑电图对139名自闭症个体和98名非自闭症个体进行评估。对于每一次试验，基线瞳孔大小（BPS）评估与当前觉醒状态一致的LC-NE张力活动，而刺激诱发的瞳孔反应（SEPR）评估估计感觉选择性的LC-NE相位活动。脑电图评估失配负波（MMN-amp）的振幅，该振幅估计了作为感觉选择性脑活动读数的前注意变化检测。通过结合频率主义和贝叶斯方法，对任务中的组间测量进行建模。
在所有组中，较高的BPS与对标准刺激和异常刺激更负的MMN-amp相关。对标准刺激更负的MMN-amp与对标准刺激更高的SEPR相关。在控制这些关联后，自闭症个体与非自闭症个体对标准刺激的SEPR更高。此外，BPS与对标准刺激的SEPR之间的正相关在自闭症个体中具有特异性。随着任务的进行，自闭症个体与非自闭症个体的BPS最初升高幅度更大，随后下降更陡峭。贝叶斯后验分布估计支持了这一点。
试验持续时间较短，需要将试验连接成时段，并应用线性时不变滤波器来捕获缓慢的瞳孔变化。由于没有对LC-NE进行操作，我们不能排除瞳孔变化是由LC-NE以外的其他皮质通路诱发的。
在所有组中，LC-NE张力上调被强调为一种普遍机制，它非特异性地增加对所有感觉刺激的前注意变化检测，进而增加对频繁刺激的感觉选择性。在自闭症个体中，不同的感觉处理方式表现为对频繁刺激的感觉选择性增加。这可能是由LC-NE张力上调引起的。它将自闭症感觉处理与觉醒上调增加联系起来，觉醒上调增加了对不显眼听觉信息的感觉选择性。
