Pupillometry in Autism Spectrum Disorders

Pupillometry, the measurement of pupil size and its dynamic changes in response to light, cognitive load and emotional stimuli, has emerged as a non-invasive window into autonomic and neuromodulatory processes in autism spectrum disorders (ASD). Studies have revealed that both the rapid constriction-dilation of the pupil and its tonic diameter can differ markedly in individuals with ASD compared with neurotypical controls. These differences appear to index atypical functioning of the cholinergic and noradrenergic systems—most notably the locus coeruleus–norepinephrine (LC-NE) pathway—alongside altered sensory processing, social attention and arousal regulation. In infancy, hypersensitive pupillary light reflexes may signal elevated risk and correlate with later symptom severity, suggesting potential for early risk assessment. In childhood and beyond, variations in pupil adaptation to sustained light and dark, task-evoked constriction latency and dilation magnitude have been linked to quantitative measures of autistic traits. Across social and non-social paradigms, pupillometry has illuminated how individuals with ASD allocate attention to sensory salience, process emotional expressions and engage cognitive resources. As methods and analysis techniques evolve, pupillometry holds promise for translational applications in screening, stratification and monitoring of interventions in ASD.

Research from Nature Portfolio

Recent studies have demonstrated that infants at elevated familial risk for ASD show an enhanced pupillary light reflex in the first year of life, exhibiting larger relative constriction compared with low-risk peers; the magnitude of this early reflex correlates with the severity of later autism symptoms. This finding supports the view that cholinergic signalling differences and early sensory atypicalities play a role in the aetiology of ASD and that pupillometry could, with further refinement, aid infant risk stratification. In older children and adolescents, novel paradigms capturing sustained pupil adaptation during alternating light and dark periods have identified distinct constriction and dilation metrics that are separable from baseline measures. Crucially, these adaptation metrics correlate with individual differences in social responsiveness scores, indicating that simple pupillometry protocols can yield physiological markers aligned with quantitative behavioural traits across the spectrum.

Pupillometry in Autism Spectrum Disorders publication trend

The graph below shows the total number of articles in pupillometry in autism spectrum disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Pupillometry: The quantitative measurement of pupil size dynamics in response to light, cognitive load or emotional stimuli, used to infer autonomic and neuromodulatory activity.

Pupillary Light Reflex (PLR): The constriction and subsequent dilation of the pupil in response to changes in ambient light intensity, largely mediated by cholinergic pathways.

Locus Coeruleus–Norepinephrine (LC-NE) System: A brainstem neuromodulatory network that regulates arousal, attention and sensory gain, influencing phasic and tonic pupil responses.

Phasic Pupil Response: A rapid, transient change in pupil diameter elicited by discrete stimuli, reflecting momentary neural and attentional processes.

Tonic Pupil Diameter: The baseline pupil size maintained over longer periods, associated with overall arousal and baseline neuromodulatory tone.

References

1. Sensory salience processing moderates attenuated gazes on faces in autism spectrum disorder: a case–control study. Molecular Autism (2023).
2. Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood. Nature Communications (2018).
3. Hypersensitive pupillary light reflex in infants at risk for autism. Molecular Autism (2015).
4. Pupil adaptation corresponds to quantitative measures of autism traits in children. Scientific Reports (2017).
5. Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD. Behavioral Sciences (2018).
6. Reactivity to fearful expressions of familiar and unfamiliar people in children with autism: an eye-tracking pupillometry study. Journal of Neurodevelopmental Disorders (2014).
7. Neuromodulation and a Reconceptualization of Autism Spectrum Disorders: Using the Locus Coeruleus Functioning as an Exemplar. Frontiers in Neurology (2018).