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
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological Psychiatry: Cognitive Neuroscience and NeuroimagingAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Arousal-biased competition in perception and memory.Perspect Psychol Sci. 2011; 6: 114-133
- Locus coeruleus: A new look at the blue spot.Nat Rev Neurosci. 2020; 21: 644-659
- Neuromodulation of attention.Neuron. 2018; 97: 769-785
- An integrative theory of locus coeruleus-norepinephrine function: Adaptive gain and optimal performance.Annu Rev Neurosci. 2005; 28: 403-450
- The effects of neural gain on attention and learning.Nat Neurosci. 2013; 16: 1146-1153
- Phasic locus coeruleus activity regulates cortical encoding of salience information.Proc Natl Acad Sci U S A. 2018; 115: E9439-E9448
- Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part I: Principles of functional organisation.Curr Neuropharmacol. 2008; 6: 235-253
- Norepinephrine ignites local hotspots of neuronal excitation: How arousal amplifies selectivity in perception and memory.Behav Brain Sci. 2016; 39 (e200–e200)
- Isometric exercise facilitates attention to salient events in women via the noradrenergic system.Neuroimage. 2020; 210: 116560
- Pupil diameter covaries with BOLD activity in human locus coeruleus.Hum Brain Mapp. 2014; 35: 4140-4154
- A meta-analysis of visual orienting in autism.Front Hum Neurosci. 2013; 7: 833
- Global processing takes time: A meta-analysis on local–global visual processing in ASD.Psychol Bull. 2015; 141: 549-573
- Impairments to visual disengagement in autism spectrum disorder: A review of experimental studies from infancy to adulthood.Neurosci Biobehav Rev. 2014; 47: 559-577
- Arousal and attention re-orienting in autism spectrum disorders: Evidence from auditory event-related potentials.Front Hum Neurosci. 2014; 8: 34
- P300 amplitude and latency in autism spectrum disorder: A meta-analysis.Eur Child Adolesc Psychiatry. 2016; 26: 177-190
- Atypical attentional networks and the emergence of autism.Neurosci Biobehav Rev. 2013; 37: 164-183
- Intra-subject variability in attention-deficit hyperactivity disorder.Biol Psychiatry. 2006; 60: 1088-1097
- The neurocognitive profile of attention-deficit/hyperactivity disorder: A review of meta-analyses.Arch Clin Neuropsychol. 2018; 33: 143-157
- A meta-analytic study of event rate effects on Go/No-Go performance in attention-deficit/hyperactivity disorder.Biol Psychiatry. 2012; 72: 990-996
- The development of state regulation in normal children: An indirect comparison with children with ADHD.Dev Neuropsychol. 1999; 16: 213-225
- The locus coeruleus—norepinephrine system as pacemaker of attention—A developmental mechanism of derailed attentional function in autism spectrum disorder.Eur J Neurosci. 2018; 47: 115-125
- Increased locus coeruleus tonic activity causes disengagement from a patch-foraging task.Cogn Affect Behav Neurosci. 2017; 10: 252-269
- Pupil diameter tracks changes in control state predicted by the adaptive gain theory of locus coeruleus function.Cogn Affect Behav Neurosci. 2010; 10: 252-269
- Motivation alters implicit temporal attention through sustained and transient mechanisms: A behavioral and pupillometric study.Psychophysiology. 2018; 55e13275
- Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex.Neuron. 2016; 89: 221-234
- Expectancy modulates pupil size during endogenous orienting of spatial attention.Cortex. 2018; 102: 57-66
- Pupil and salivary indicators of autonomic dysfunction in autism spectrum disorder.Dev Psychobiol. 2013; 55: 465-482
- Adults with autism overestimate the volatility of the sensory environment.Nat Neurosci. 2017; 20: 1293-1299
- Uncharacteristic task-evoked pupillary responses implicate atypical locus coeruleus activity in autism.J Neurosci. 2020; 40: 3815-3826
- Pupil size tracks attentional performance in attention-deficit/hyperactivity disorder.Sci Rep. 2017; 7: 8228
- Autism spectrum disorder and pupillometry: A systematic review and meta-analysis.Neurosci Biobehav Rev. 2021; 120: 479-508
- Pupil dilation during visuospatial orienting differentiates between autism spectrum disorder and attention-deficit/hyperactivity disorder.J Child Psychol Psychiatry. 2019; 61: 614-624
- A multifaceted investigation of the link between mental fatigue and task disengagement.Psychophysiology. 2015; 52: 305-315
- Context-dependent dynamic processes in attention-deficit/hyperactivity disorder: Differentiating common and unique effects of state regulation deficits and delay aversion.Neuropsychol Rev. 2010; 20: 86-102
- Testing assumptions for endophenotype studies in ADHD: Reliability and validity of tasks in a general population sample.BMC Psychiatry. 2005; 5: 40
- Response time variability under slow and fast-incentive conditions in children with ASD, ADHD and ASD+ADHD.J Child Psychol Psychiatry. 2016; 57: 1414-1423
- WISC-IV: Wechsler Intelligence Scale for Children: Deutschsprachige Adaptation nach D. Wechsler.Pearson Assessment and Information, Frankfurt, Germany2011
- Wechsler Adult Intelligence Scale–fourth edition (WAIS-IV). Deutschsprachige Adaptation der WAIS-IV von D Wechsler.Pearson Assessment and Information, Frankfurt, Germany2012
- Discriminant validity of the Child Behaviour Checklist CBCL-4/18 in German samples.Eur Child Adolesc Psychiatry. 2001; 10: 240-247
- Diagnostic and Statistical Manual of Mental Disorders.5th ed. American Psychiatric Association, Washington, DC2013
- Schedule for affective disorders and schizophrenia for school-age children–present and lifetime version (K-SADS-PL): Initial reliability and validity data.J Am Acad Child Adolesc Psychiatry. 1997; 36: 980-988
- Diagnostische Beobachtungsskala für Autistische Störungen (ADOS). Bern.Verlag Hans Huber, Switzerland2004
- Diagnostisches Interview für Autismus—Revidiert. Bern.Verlag Hans Huber, Switzerland2006
- Assessing autistic traits: Cross-cultural validation of the Social Responsiveness Scale (SRS).Autism Res. 2008; 1: 354-363
- DISYPS-KJ: Diagnostik-System für psychische Störungen im Kindes-und Jugendalter nach ICD-10 und DSM-IV; klinische Diagnostik-Elternurteil-Erzieher-und Lehrerurteil-Selbsturteil; Manual. Bern.Verlag Hans Huber, Switzerland2000
- Preprocessing pupil size data: Guidelines and code.Behav Res Methods. 2018; 51: 1336-1342
- Safe and sensible preprocessing and baseline correction of pupil-size data.Behav Res Methods. 2018; 50: 94-106
- Pupil diameter predicts changes in the exploration–exploitation trade-off: Evidence for the adaptive gain theory.J Cogn Neurosci. 2011; 23: 1587-1596
- Pupillary responses and reaction times index different cognitive processes in a combined Go/Switch incidental learning task.Neuropsychologia. 2019; 127: 48-56
- Pupillometry reveals a mechanism for the Autism Spectrum Disorder (ASD) advantage in visual tasks.Sci Rep. 2014; 4: 4301
- Ggplot2: Elegant graphics for data analysis.Springer, London, UK2016
- Fitting linear mixed-effects models using lme4.J Stat Softw. 2015; 67
- Least-squares means: The R package lsmeans.J Stat Softw. 2016; 69
- LmerTest package: Tests in linear mixed effects models.J Stat Softw. 2017; 82
- papaja: Create APA manuscripts with R Markdown.(Available at:)
- SIMR: An R package for power analysis of generalized linear mixed models by simulation.Methods Ecol Evol. 2016; 7: 493-498
- sjplot: Data visualization for statistics in social science. R package version 2.8.7.(Available at:)
- Resting and functional pupil response metrics indicate features of reward sensitivity and ASD in children.J Autism Dev Disord. 2021; 51: 2416-2435
- Reaction time variability in ADHD: A meta-analytic review of 319 studies.Clin Psychol Rev. 2013; 33: 795-811
- Larger tonic pupil size in young children with autism spectrum disorder.Dev Psychobiol. 2009; 51: 207-211
- Tonic noradrenergic activity modulates explorative behavior and attentional set shifting: Evidence from pupillometry and gaze pattern analysis.Psychophysiology. 2017; 54: 1839-1854
- Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder.J Child Psychol Psychiatry. 2021; 62: 149-159
Article info
Publication history
Published online: April 26, 2021
Accepted:
April 15,
2021
Received in revised form:
April 15,
2021
Received:
December 10,
2020
Identification
Copyright
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
