Idiosyncratic pupil regulation in autistic children

Abstract

Recent neuroimaging and eye tracking studies have suggested that children with autism spectrum disorder (ASD) may exhibit more variable and idiosyncratic brain responses and eye movements than typically developing (TD) children. Here we extended this research for the first time to pupillometry recordings. We successfully completed pupillometry recordings with 103 children (66 with ASD), 4.5-years-old on average, who viewed three 90 second movies, twice. We extracted their pupillary time-course for each movie, capturing their stimulus evoked pupillary responses. We then computed the correlation between the time-course of each child and those of all others in their group. This yielded an average inter-subject correlation value per child, representing how similar their pupillary responses were to all others in their group. ASD participants exhibited significantly weaker inter-subject correlations than TD participants, reliably across all three movies. Differences across groups were largest in responses to a naturalistic movie containing footage of a social interaction between two TD children. This measure enabled classification of ASD and TD children with a sensitivity of 0.82 and specificity of 0.73 when trained and tested on independent datasets. Using the largest ASD pupillometry dataset to date, we demonstrate the utility of a new technique for measuring the idiosyncrasy of pupil regulation, which can be completed even by young children with co-occurring intellectual disability. These findings reveal that a considerable subgroup of ASD children have significantly more unstable, idiosyncratic pupil regulation than TD children, indicative of more variable, weakly regulated, underlying neural activity.

Figure 1:

Tonic pupil diameter (mm) in each of the six movies. A. Scatter plot demonstrating tonic pupil diameter for each individual, across both groups, per movie. Black line: mean tonic pupil diameter per group. There were no significant differences across groups. B-D. Scatter plots demonstrating stability of tonic pupil diameter per participant across two presentations of each movie. Each point represents a single child. Solid lines: Least squares fit. Dotted line: unity line. Blue: ASD, Gray: TD.

Figure 2:

Time-courses of pupil diameter from each presentation of the three movies. A, C, E: First presentation. B, D, F: Second presentation. Solid line: average pupil diameter across participants per group. Shaded area: standard error of the mean. Blue: ASD. Gray: TD.

Figure 3:

Comparison of inter-subject correlation values across groups for each movie and presentation. A: First presentation. B: Second presentation. Blue: ASD, Gray: TD. Asterisks: Significant differences across groups according to ANCOVA tests (*p<0.05, **p<0.01, ***p<0.001).

Figure 4:

Scatter plots of inter-SC values demonstrating their correlation across the two presentations of Jack-Jack Attack (A), Jungle Book (B), and Naturalistic (C) movies. Blue: ASD, Gray: TD. Solid lines: Least squares fit. Dotted line: unity line.

Figure 5:

ROC analyses using inter-SC to classify ASD and TD participants. A: First presentation. B: Second presentation. Vertical dashed lines represent the optimal classification threshold as determined using Youden’s J statistic for the Jack-Jack Attack (purple), Jungle Book (yellow), and Naturalistic (red) movies. Optimal classification thresholds were determined with data from the first presentation (left panel) and their accuracy was tested with data from the second presentation (right panel). Black dashed line: unity line.