Temporal progression of pupil dilation and gaze behavior to emotion expressions in preschoolers with autism spectrum disorder.

Previous work has shown divergent pupil dilation (PD) and gaze behavior in individuals with autism spectrum disorder (ASD), which may relate to the development of social difficulties in early life. Here, we investigated temporal dynamics of both phenotypes during naturalistic videos of a person displaying facial emotion expressions in 61 autistic and 61 non-autistic preschoolers. PD was segmented into three serial time components derived from a principal component analysis. Growth curve analysis was applied to analyze changes in looking time on eye and mouth regions over time. Groups did not differ in PD time components. Growth curve analysis revealed initially shorter looking times on the eyes and longer looking times on the mouth in autistic versus non-autistic preschoolers. However, a reversion of this pattern was observed over time, suggesting a delayed compensatory increase in eye attention during prolonged viewing periods in autistic children. Positive and negative associations of PD components and gaze behavior over time indicated a dynamic temporal relationship during emotion viewing. Our findings emphasize the need to apply time-sensitive measures in ecologically valid research, which may index etiological mechanisms of social difficulties in ASD.

Atypical Arousal Regulation in Children With Autism but Not With Attention-Deficit/Hyperactivity Disorder as Indicated by Pupillometric Measures of Locus Coeruleus Activity.

BACKGROUND: Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. The locus coeruleus-norepinephrine system (LC-NE) underlies arousal regulation and adapts its activity to the utility of a task. LC-NE tonic and phasic activity are indexed by baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR). METHODS: The study assessed pupillometry in ASD (n = 31, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) during a visuospatial reaction-time task that manipulates arousal by conditions with low and high task utility. We estimated linear mixed models of BPS, SEPR, and MRT in a per-trial analysis to investigate arousal regulation of task performance. RESULTS: Slower MRT occurred in the ASD group compared with the typically developing control group during low-utility conditions while controlling for dimensional ASD and attention-deficit/hyperactivity disorder symptoms. In low-utility conditions, BPS and SEPR were inversely related and both were associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low-utility conditions. Changes in BPS and SEPR between task-utility conditions were smaller in the ASD group. CONCLUSIONS: Slower visuospatial task performance in ASD is specific to low task utility. Arousal was associated with task performance and showed altered activity in ASD. Increased BPS during low-utility conditions suggested increased LC-NE tonic activity as an ASD symptom marker in children. Smaller changes in BPS and SEPR in ASD indicated attenuated LC-NE activity adaptation in response to high-utility conditions. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.

Pupillometric measures of altered stimulus-evoked locus coeruleus-norepinephrine activity explain attenuated social attention in preschoolers with autism spectrum disorder.

Attenuated social attention has been described as a reduced preference for social compared to geometric motion in preschoolers with autism spectrum disorder (ASD). The locus coeruleus-norpinephrine (LC-NE) system modulates sensory reactivity and is a promising underlying mechanism. LC-NE activity is indexed by a stimulus-evoked pupillary response (SEPR) and partially by a luminance-adaptation pupillary response (LAPR), which were both shown to be aberrant in ASD. We examined whether SEPR and LAPR explain an attenuated social motion preference. We applied pupillometry via video-based eye tracking in young children (18-65 months) with ASD (n = 57) and typically developing (TD) children (n = 39) during a preferential looking paradigm of competing social and geometric motion and a changing light condition paradigm. We found an attenuated social motion preference in the ASD compared to the TD group. This was accompanied by atypical pupillometry showing a smaller SEPR to social motion, a larger SEPR to geometric motion and a reduced LAPR to a dark screen. SEPR but not LAPR explained the group difference in social motion preference. An ASD diagnosis was statistically predicted by the social motion preference, while this effect was mediated by the inclusion of SEPR to geometric and social motion. Our findings suggest a decreased sensory reactivity to social and increased reactivity to non-social motion in ASD, which may concurrently contribute to an attenuated social attention. The LC-NE system is supported as a promising underlying mechanism of altered social attention in young children with ASD, while the specificity of findings remains to be addressed.

Pupil dilation during visuospatial orienting differentiates between autism spectrum disorder and attention-deficit/hyperactivity disorder.

BACKGROUND: Previous research demonstrated atypical attention in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Regarding visual orienting, findings suggest a differential impairment: Atypical orienting to relatively unexpected targets in ASD, and atypical processing of alerting cues in ADHD. The locus coeruleus-norepinephrine (LC-NE) system plays an important role in exploiting alerting cues to increase attention and task performance. The present study's aim was to examine differential subcortical processes underlying visual orienting in ASD and ADHD with pupil dilation (PD) as index of LC activity. METHODS: Pupil dilation (PD) progression metrics during visual orienting were calculated for task-evoked PD locked to cue, stimulus onset, and behavioral response. Group differences in PD and reaction time (RT) were compared between children with ASD without ADHD (ASD-) (N = 18), ADHD without ASD (ADHD-) (N = 28), both disorders (ASD + ADHD) (N = 14), and typically developing children (TD) (N = 31) using linear mixed models (LMM). To further explore the modulatory role of the LC-NE system group differences in the effect of task-evoked PD metrics on RT were examined exploratively. RESULTS: ASD (+ADHD) showed slower orienting responses to relatively unexpected spatial target stimuli as compared to TD, which was accompanied by higher PD amplitudes relative to ADHD- and TD. In ADHD-, shorter cue-evoked PD latencies relative to ASD-, ASD + ADHD, and TD were found. Group differences in the effect of cue- and stimulus-evoked PD amplitudes on RT were found in ASD- relative to TD. CONCLUSIONS: Study findings provide new evidence for a specific role of the LC-NE system in impaired reflexive orienting responses in ASD, and atypical visual processing of alerting cues in ADHD.