Pupil dilation during visuospatial orienting differentiates between autism spectrum disorder and attention‐deficit/hyperactivity disorder

Abstract

Background: Previous research demonstrated atypical attention in children with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Regarding visual orienting, findings suggest a differential impairment: Atypical orienting to relatively unexpected targets in ASD, and atypical processing of alerting cues in ADHD. The locus coeruleus-norepinephrine (LC-NE) system plays an important role in exploiting alerting cues to increase attention and task performance. The present study's aim was to examine differential subcortical processes underlying visual orienting in ASD and ADHD with pupil dilation (PD) as index of LC activity. Methods: Pupil dilation (PD) progression metrics during visual orienting were calculated for task-evoked PD locked to cue, stimulus onset, and behavioral response. Group differences in PD and reaction time (RT) were compared between children with ASD without ADHD (ASD-) (N = 18), ADHD without ASD (ADHD-) (N = 28), both disorders (ASD + ADHD) (N = 14), and typically developing children (TD) (N = 31) using linear mixed models (LMM). To further explore the modulatory role of the LC-NE system group differences in the effect of task-evoked PD metrics on RT were examined exploratively. Results: ASD (+ADHD) showed slower orienting responses to relatively unexpected spatial target stimuli as compared to TD, which was accompanied by higher PD amplitudes relative to ADHDÀ and TD. In ADHDÀ, shorter cue-evoked PD latencies relative to ASDÀ, ASD + ADHD, and TD were found. Group differences in the effect of cueand stimulus-evoked PD amplitudes on RT were found in ASDÀ relative to TD. Conclusions: Study findings provide new evidence for a specific role of the LC-NE system in impaired reflexive orienting responses in ASD, and atypical visual processing of alerting cues in ADHD. Key pointsPrevious findings suggest different attention processes during visuospatial orienting task performance in ASD and ADHD. This is the first study to compare pupil dilations (PD) as an index of LC activity between ASD and ADHD during visuospatial orienting.PD during visuospatial orienting differentiated between ASD and ADHD, suggesting different subcortical processes in ASD and ADHD.

Autism spectrum disorder and pupillometry: A systematic review and meta-analysis

“…Delayed orienting of attention could be reflected by a delayed latency in the study by Bast et al, which would be in agreement with the known delayed orienting in ASD in behavioural tasks (Bast et al, 2019). Boxhoorn et al (2020) suggest increased pupil dilation is a result of a persistent hyperphasic state, with enhanced attentional focus, but also reflects increased task difficulty or cognitive load, which as a result leads them to interpret increased pupil dilation in the ASD group in their study as a higher effort to control the focus of attention during reflexive orienting in ASD. Del Valle Rubido et al (2020) suggest pupil size might reflect the ability to better arrange effortful attention and interpret this as a sign of greater cognitive or inhibitory control, even though this appears to be inconsistent with their own results.…”

Uncharacteristic Task-Evoked Pupillary Responses Implicate Atypical Locus Ceruleus Activity in Autism

“…A recent review from Bast et al (2018) suggests that LC dysfunction might be associated with attentional differences in ASD, but there has been little prior empirical evidence to support this hypothesis. Several studies have shown phasic pupillary response differences in ASD (Martineau et al, 2011;Blaser et al, 2014;Nuske et al, 2014a,b;Krach et al, 2015;Lawson et al, 2017;Aguillon-Hernandez et al, 2019;Boxhoorn et al, 2019). However, in these studies, participants with ASD exhibited differences in task performance compared with controls; thus, differences in pupil dilations may be attributable to differences in task performance.…”

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

“…The LC is the main location of a highly flexible, adaptable noradrenergic system projecting in many cortical and subcortical brain regions, thus explaining its highly relevant function in humans in everyday life, and essential for us humans as feeling and thinking beings. Beside its involvement in cognitive processes, a broader function recently emerged covering aspects of psychopathology, such as triggering anxiety (Morris et al, 2020), psychosis in alpha-synucleinopathies (Wolters, 2001) and demotivation in schizophrenia (Mäki-Marttunen et al, 2020), inattention to visual stimuli in the attention deficit-hyperactivity and autism-spectrum disorders (Boxhoorn et al, 2020), depressive symptoms in Alzheimer's disease (AD) (Förstl et al, 1992), suicide behavior (Roy et al, 2017) and defective emotional-memory encoding (Jacobs et al, 2020).…”