The locus coeruleus-norepinephrine system as pacemaker of attention - a developmental mechanism of derailed attentional function in autism spectrum disorder

Bast, Nico; Poustka, Luise; Freitag, Christine M.

doi:10.1111/ejn.13795

Cited by 121Autism Spectrum Disorder ResearchAttention Deficit Hyperactivity DisorderNeural and Behavioral Psychology Studies

The locus coeruleus-norepinephrine system as pacemaker of attention - a developmental mechanism of derailed attentional function in autism spectrum disorder

Bast, Nico, Poustka, Luise, Freitag, Christine M.·2018·European Journal of Neuroscience

DOI 10.1111/ejn.13795

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Abstract

Children with autism spectrum disorder (ASD) exhibit diminished visual engagement to environmental stimuli. Aberrant attentional function provides an explanation by reduced phasic alerting and orienting to exogenous stimuli. We review aberrant attentional function (alerting, orienting and attentional control) in children with ASD as studied by neurocognitive and neurophysiological tasks as well as magnetic resonance imaging studies. The locus coeruleus-norepinephrine (LC-NE) system is outlined as a pacemaker of attentional function. The LC-NE system regulates adaptive gain in synaptic signal transmission, which moderates phasic alerting ('promoting') and the activation of the ventral frontoparietal attention network within orienting ('permitting'). In children with ASD, atypical LC-NE activity is proposed as underlying mechanism of aberrant attentional function. It may manifest as (i) increased tonic activity with reduced phasic reactivity to exogenous stimuli, (ii) attenuated bottom-up signalling mitigating salience and predictive reward attribution during phasic alerting, and (iii) reduced activation of the ventral frontoparietal attention system attenuating orienting to exogenous stimuli. Increased tonic pupil dilation and aberrant pupil reactivity are discussed as indicators of atypical LC-NE activity. Pupillometry is outlined as feasible method to assess alerting, orienting and attentional control that can be dissected from the pupil dilation time course. In children with ASD, aberrant attentional function through atypical LC-NE activity is proposed as developmental mechanism leading to reduced social attention as well as social interaction and communication impairments.

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Pupil constriction and dilation are influenced by activity in the SNS and PNS.
“Similarly, the constriction and dilation of the pupil are influenced by activity in the SNS and the PNS (Bast et al., 2018)”
From Is autonomic nervous system function atypical in Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the evidence (2020) · cites this paper as Bast et al., 2018
Measuring pupil size during resting-state or cognitive tasks is likely to give an indication of ANS activity.
“Therefore, measuring pupil size during resting-state or cognitive tasks is likely to give an indication of ANS activity (Bast et al., 2018).”
From Is autonomic nervous system function atypical in Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the evidence (2020) · cites this paper as Bast et al., 2018

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“Closing the loop, top-down signalling initiates a phasic alerting response with NE release (Kalwani et al., 2014) and transient spiking of LC activity (phasic LC–NE activity; Joshi et al., 2016; M€uckschel et al., 2016).”
BackgroundMethodInfluential
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Increased locus coeruleus tonic activity causes disengagement from a patch-foraging task
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Prefrontal Norepinephrine Determines Attribution of “High” Motivational Salience
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Brain responses to biological motion predict treatment outcome in young children with autism
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The norepinephrine system affects specific neurophysiological subprocesses in the modulation of inhibitory control by working memory demands
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Zoom-out attentional impairment in children with autism spectrum disorder
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Pupillometry reveals reduced unconscious emotional reactivity in autism
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A meta-analysis of visual orienting in autism
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Diminished social reward anticipation in the broad autism phenotype as revealed by event-related brain potentials
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Validation of the Movie for the Assessment of Social Cognition in Adolescents with ASD: Fixation Duration and Pupil Dilation as Predictors of Performance
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An Event-Related Potential Investigation of the Effects of Age on Alerting, Orienting, and Executive Function
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Greater Pupil Size in Response to Emotional Faces as an Early Marker of Social‐Communicative Difficulties in Infants at High Risk for Autism
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Distinct Frontoparietal Networks Underlying Attentional Effort and Cognitive Control
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The effect of emotional intensity on responses to joint attention in preschoolers with an autism spectrum disorder
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Multisensory signalling enhances pupil dilation
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Rebalancing Spatial Attention: Endogenous Orienting May Partially Overcome the Left Visual Field Bias in Rapid Serial Visual Presentation
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Attentional Networks in Adolescents with High-functioning Autism: An fMRI Investigation
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Neural Correlates of Explicit Versus Implicit Facial Emotion Processing in ASD
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Specificity of autonomic arousal to anxiety in children with autism spectrum disorder
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Modafinil enhances alerting-related brain activity in attention networks
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GABA levels in the ventromedial prefrontal cortex during the viewing of appetitive and disgusting food images
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Causal Role of Noradrenaline in the Timing of Internally Generated Saccades in Monkeys
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A genetically encoded fluorescent sensor for rapid and specific in vivo detection of norepinephrine
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Can pupillometry distinguish accurate from inaccurate familiarity?
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Speech recognition in noise task among children and young-adults: a pupillometry study
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Authors: Bast, N., Poustka, L., & Freitag, C. M.
Affiliations: Goethe University Frankfurt (DE)
Heidelberg University (DE)
Corresponding author: Bast, Nico
ORCID: Bast, Nico
Poustka, Luise
Freitag, Christine M.
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2018-01
Volume: 47
Issue: 2
Pages: 115-125
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/ejn.13795
OpenAlex: W2772713599
Cited by: 121
References: 172
Citations by year: 2026: 11 · 2025: 10 · 2024: 8 · 2023: 33 · 2022: 10 · 2021: 17 · 2020: 19 · 2019: 11 · 2018: 2
FWCI: 0.98
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 9 d)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: autism spectrum disorder, locus coeruleus, norepinephrine, attention, alerting, orienting, attentional control, bottom-up salience, pupil reactivity, pupillometry, social attention, children
MeSH terms: Autism Spectrum Disorder, Attention, Biological Clocks, Humans, Locus Coeruleus, Norepinephrine

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The locus coeruleus-norepinephrine system as pacemaker of attention - a developmental mechanism of derailed attentional function in autism spectrum disorder

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