Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case–control study
Authors: Bast Nico , Mason Luke , Ecker Christine , Baumeister Sarah , Banaschewski Tobias , Jones Emily J. H. , Murphy Declan G. M. , Buitelaar Jan K. , Loth Eva , Pandina Gahan ,   the EU-AIMS LEAP Group, Ahmad Jumana , Ambrosino Sara , Auyeung Bonnie , Banaschewski Tobias , Baron-Cohen Simon , Bast Nico , Baumeister Sarah , Beckmann Christian F. , Bölte Sven , Bourgeron Thomas , Bours Carsten , Brammer Michael , Brandeis Daniel , Brogna Claudia , de Bruijn Yvette , Buitelaar Jan K. , Chakrabarti Bhismadev , Charman Tony , Cornelissen Ineke , Crawley Daisy , Dell’Acqua Flavio , Dumas Guillaume , Durston Sarah , Ecker Christine , Faulkner Jessica , Frouin Vincent , Garcés Pilar , Goyard David , Ham Lindsay , Hayward Hannah , Hipp Joerg , Holt Rosemary , Johnson Mark , Jones Emily J. H. , Kundu Prantik , Lai Meng-Chuan , D’ardhuy Xavier Liogier , Lombardo Michael V. , Loth Eva , Lythgoe David J. , Mandl René , Marquand Andre , Mason Luke , Mennes Maarten , Meyer-Lindenberg Andreas , Moessnang Carolin , Murphy Declan G. M. , Oakley Bethany , O’Dwyer Laurence , Oldehinkel Marianne , Oranje Bob , Pandina Gahan , Persico Antonio M. , Ruggeri Barbara , Ruigrok Amber , Sabet Jessica , Sacco Roberto , Cáceres Antonia San José , Simonoff Emily , Spooren Will , Tillmann Julian , Toro Roberto , Tost Heike , Waldman Jack , Williams Steve C. R. , Wooldridge Caroline , Zwiers Marcel P. , Freitag Christine M. 
Published: February 2023

Abstract
Background
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.

Methods
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.

Results
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.

Limitations
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.

Conclusions
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.