Atypical Arousal Regulation in children with Autism but not with ADHD as indicated by pupillometric measures of Locus Coeruleus Activity

Abstract Background Atypical arousal regulation may explain slower mean reaction times (MRT) in Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) compared to typically developing controls (TD). 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, 3F/28M), ADHD (n=28, 3F/25M) and TD (n=31, 16F/15M) 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 ASD compared to TD during low utility, while controlling for dimensional ASD and ADHD symptoms. Regarding low utility, BPS and SEPR were inversely related and both associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low utility. 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 suggested increased LC-NE tonic activity as ASD symptom marker in children. Smaller BPS and SEPR changes in ASD indicated attenuated LC-NE activity adaptation in response to high utility. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.