EEG and Pupillary Response in Children with Autism: Results from the ABC-CT Interim Analysis

Background: Dysregulated attention and arousal are comorbid features of ASD. These symptoms are associated with differences in noradrenergic activity. Prior work has established that individuals with ASD exhibit attenuated pupil response to light. Despite the broad noradrenergic efferents from the LC to cortex, there have been no studies in humans linking the dynamics of the pupillary light reflex (PLR) to electroencephalography (EEG) features; this relationship may help to parse heterogeneity among individuals with ASD and differentiate brain activity between ASD and controls.

Objectives: We examine: (1) the relationship of the PLR and EEG; (2) the relationship of the PLR and EEG to clinical characteristics; and (3) the relationship of the EEG slope, an index of excitatory versus inhibitory activity in the cortex, to the PLR.

Methods: Data were collected from 225 participants between the ages of 6 and 11 (ASD: N = 161, 131 male; TD: N = 64, 42 male) across five sites. EEG data were recorded at 1000hz, and spectral power was calculated from one second epochs. EEG slope was calculated in the range from 2-50hz. The PLR was calculated in response to a 133ms white flash followed by a black screen. PLR dynamics included relative constriction, latency of constriction, and re-dilation and constriction velocities.

Results: Across all participants and sites, absolute EEG power in all frequency bands decreased with increasing age; thus, age was included as a covariate in all regression analyses. Overall, there was no relationship between the relative constriction amplitude of the PLR and EEG characteristics. However, the latency of the PLR was negatively associated with low (8-10hz; p=.026) and high (10-12hz; p = .042) alpha power and the slope of the EEG power spectrum (p=.01), such that longer latency PLR was associated with decreased alpha power and a more positive slope indicating greater high frequency activity associated with increased cortical excitation. With regard to clinical characteristics, ADOS calibrated severity score was associated with increased power across the delta, theta, beta, and gamma frequency bands (rs = .16, .15, .15, .21; ps =.015, .024, .042, .002, respectively).

Conclusions:

These data provide support for moderate but significant relationships between the dynamics of PLR constriction and cortical activity in ASD. Because these effects are detectable across separate recording sessions on different days, it is unlikely that they are driven by common stimulus effects, e.g., phasic arousal or ambient light. Instead, they likely reflect relatively stable, trait-like relationships among neuromodulatory systems and cortical brain activity. The relationship with PLR and the slope of the power spectrum suggests that these relationships impact the overall shape of the EEG power spectrum and that effects go beyond simple modulation of amplitude of oscillatory activity. Given that cholinergic and noradrenergic systems are the targets of multiple medications, these findings have the potential to inform novel mechanisms of assessing therapeutic effects. Ongoing analyses measure the strength of the association within individuals and its relationship with clinical characteristics.