Atypical Arousal Regulation in Children With Autism but Not With Attention-Deficit/Hyperactivity Disorder as Indicated by Pupillometric Measures of Locus Coeruleus Activity

Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Jan;8(1):11-20. doi: 10.1016/j.bpsc.2021.04.010. Epub 2021 Apr 27.

Abstract

Background: Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. 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, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) 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 the ASD group compared with the typically developing control group during low-utility conditions while controlling for dimensional ASD and attention-deficit/hyperactivity disorder symptoms. In low-utility conditions, BPS and SEPR were inversely related and both were associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low-utility conditions. 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 conditions suggested increased LC-NE tonic activity as an ASD symptom marker in children. Smaller changes in BPS and SEPR in ASD indicated attenuated LC-NE activity adaptation in response to high-utility conditions. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.

Keywords: ASD; Attention-deficit/hyperactivity disorder; Endophenotype; Pupillary response; Sensory processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arousal / physiology
  • Attention Deficit Disorder with Hyperactivity* / complications
  • Autism Spectrum Disorder* / complications
  • Autistic Disorder*
  • Child
  • Female
  • Humans
  • Locus Coeruleus / physiology
  • Male