Measures of tonic and phasic activity of the locus coeruleus—norepinephrine system in children with autism spectrum disorder: An event‐related potential and pupillometry study

A growing body of research suggests that locus coeruleus‐norepinephrine (LC‐NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event‐related potential [ERP]) indices may provide meaningful insights about the nature of LC‐NE function in ASD. Twenty‐four children with ASD and 27 age‐ and nonverbal‐IQ matched typically developing (TD) children completed two experiments: (1) a resting eye‐tracking task to measure tonic pupil diameter, and (2) a three‐stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC‐NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC‐NE indices were primarily related to measures of attention‐deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC‐NE activation may be associated with atypical arousal and decreased responsivity to behaviorally‐relevant information in ASD. Lay Summary The locus coeruleus (LC), a small brain stem nucleus, is the primary source of norepinephrine (NE), plays an important role in attention and arousal, and may function differently in autism spectrum disorder (ASD). Using pupillometry and event‐related potentials, we found that children with ASD show increased tonic and reduced phasic LC‐NE activation compared to their typically developing peers. These differences in LC‐NE function may be associated with impairments in attention and arousal regulation in ASD.