Attentional Disengagement and the Locus Coeruleus – Norepinephrine System in Children with Autism Spectrum Disorder

Background: Differences in non-social attentional functions have been identified as among the earliest features that distinguish infants who develop autism spectrum disorder (ASD), and may play a critical role in the emergence of core ASD symptoms. Specifically, slowed attentional disengagement and difficulty reorienting attention have also been found across the lifespan in those at risk for, or diagnosed with, ASD. In addition, the locus coeruleus-norepinephrine (LC-NE) system, which is known to play an important role in arousal regulation and selective attention, has been shown to function atypically in ASD. For example, indices of LC-NE activity, such as pupil diameter and P3 amplitude, differ in individuals with ASD. However, exactly how atypical LC-NE activity relates to impairments in attentional disengagement in ASD has not been determined.

Objectives: To assess the role that the LC-NE system plays in manifestation of atypical attentional processes in children with ASD.

Methods: Participants were 23 children with ASD and 15 age- and IQ-matched typically developing (TD) children. The study consisted of separate gap-overlap and baseline eye-tracking paradigms. In the gap-overlap task, participants were instructed to fixate on a central crosshair and then move their eyes to a peripheral target once it appeared. Each trial began with a crosshair presented alone in the center of the display. Following fixation on the crosshair, a peripheral target could appear with either the crosshair remaining on the screen (overlap condition) or 200ms after the crosshair disappeared (gap condition). There were 16 possible target locations arranged on two invisible concentric circles (8 per circle); circles surrounded the fixation cross at eccentricities of 4.9° (near) and 9.8° (far). For the baseline eye-tracking paradigm, a black central crosshair was presented on a grey background, and participants were instructed to relax, remain still, and to look at the crosshair. Latency of participants’ saccades and pupil diameter were monitored using an EyeLink 1000 Plus remote eye-tracking system.

Results: Groups did not differ on overall saccadic response time (RT). Children were faster to shift attention to targets in the gap compared to the overlap condition (p < .05). There was also a marginally significant interaction between group and condition (p < .1). Saccadic RT difference scores (overlap – gap, i.e., gap effect) for ASD and TD children revealed that children with ASD showed larger difference scores for near (ASD = 100ms; TD = 44ms; p < .05) but not far (ASD = 106ms; TD = 69ms; p = .33) targets. Baseline pupil measures revealed that individuals with ASD had increased pupil dilation compared to their TD peers (p < .1). Correlational analyses showed that decreased disengagement efficiency (i.e., larger gap effect) was associated with increased pupil diameter (r = .31, p < .1).

Conclusions: Consistent with prior reports, our preliminary results show that children with ASD exhibit slowed attentional disengagement and increased arousal. Associations between measures of disengagement efficiency and pupil dilation suggest that atypically increased tonic activation of the LC-NE system may be associated with poorer attentional disengagement in children with ASD.