Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case-control study

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.

Keywords: ASD; Computer vision; Eye tracking; Locus coeruleus; Naturalistic visual attention; Norepinephrine; Pupillometry; Saliency maps; Social attention; Visual exploration.

Fig. 1

Sample flowchart. The raw data of n = 543 were available. We excluded data at the participant level, based on the depicted criteria in Methods. ASD = Autism spectrum disorder, TD = neurotypical controls, Hz = eye-tracker sampling rate, ADOS CSS = Autism Diagnostic Observation Schedule (ADOS-2) Calibrated Severity Score

Fig. 2

Data processing workflow. Schematic description of the data processing and analysis procedures. a Experimental data: Scene frames and eye-tracking raw data were linked by timestamps. b Data processing: Scene frames were transformed into two saliency maps by salience estimation algorithms (physical salience, motion salience) and the areas of interest (eyes, mouth, face, body) which were manually defined. Eye-tracking raw data were preprocessed according to recent recommendations [69], and gaze information was estimated by Grafix Software [68]. c Statistical analysis: Individual gaze information was matched to both saliency maps and areas of interest and related in the linear mixed models to pupillary reactivity as a proxy of LC-NE phasic activity

Fig. 3

Gaze behavior between groups on the nine naturalistic videos. Gaze behavior represents gaze locations as fixations on the screen that are visualized as heatmaps. Blue colors represent a low number of fixations; green colors represent an average number of fixations; and red colors represent a high number of fixations on the respective video. Of note, the naturalistic videos are segmented to individual scenes in the statistical analysis

Fig. 4

Comparison of physical salience, motion salience and luminance across scenes. The x-axis represents the progression of the video scenes (0–5000 ms), and the y-axis represents the extracted estimates of physical salience (top) or motion salience (middle) or luminance (bottom). The estimates are provided in percentage values of total possible salience or luminance in the current frame. Solid lines represent general additive model fits and shaded areas represent 95% confidence intervals. The physical and motion salience represent overall scene salience estimates of the current frame, which are different to the measures of gazes on physical and gazes on motion salience that represent salience estimates of the current gaze location and are applied in the statistical analysis

Fig. 5

Progression of key variables aggregated across scenes. Magenta: neurotypical controls (TD); purple: individuals with autism spectrum disorder (ASD). Solid lines represent general additive model fits, and shaded areas represent 95% confidence intervals

Fig. 6

Temporal effects in SSP. The x-axis represents the progression of the video scenes (0–5000 ms), and the y-axis represents the estimated marginalized means of standardized effects. Boxplot whiskers correspond to ± 2 standard errors, and the interquartile range corresponds to ± 1 standard error. Boxplots separated by video category or group are displayed side by side for each time point to avoid overplotting. a The effect of pupillary response on gazes on motion salience. b The effect of group on pupillary response. Boxplots represent effect size contrasts [ASD-TD]. c The effects of gazes on physical salience on social attention

Fig. 7

Group differences in gazes on faces are modulated by SSP. a Group difference in gazes on faces between ASD and TD as index of social attention. b Gazes on physical salience are associated with the group difference in gazes on faces. c Pupillary response moderated the group difference in gazes on faces. n.s. = not significant