Autism and the Dysregulated Arousal System

By Rebecca Grzadzinski, Kattia Mata, and Jose Rodriguez-Romaguera, The Carolina Institute for Developmental Disabilities - UNC IDDRC

May 15, 2023

AUCD's network of Intellectual and Developmental Disability Research Centers (IDDRCs) consists of 16 Centers. Fifteen Centers currently receive funding from the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD). IDDRCs contribute to the development and implementation of evidence-based practices by evaluating the effectiveness of biological, biochemical, and behavioral interventions; developing assistive technologies; and advancing prenatal diagnosis and newborn screening.

How do babies learn to be social? Babies are born into the world with so much to learn, from basic body movements to complex communication and interaction skills. Philosopher John Locke believed that babies are born into the world as “blank slates” (tabula rasas)—everything to learn will be gained from their environment and experience1. Indeed, environment and experience are critical for learning—studies on enriched environments highlight this2,3. However, research continues to highlight the influence of inherent characteristics, underlying neurobiology and genetics on how and what we learn or know4. Researchers aim to understand what and how we learn by studying the dynamic interplay between inherent biological traits, physiological states, and the environment4.

Consider the complex environment an infant is exposed to at any moment, an environment that has constantly changing sensory stimuli—auditory, tactile, olfactory, proprioceptive, and visual. How does an infant determine what information is important? What information does an infant choose to learn from amongst that complex sensory environment? Psychologist B.F. Skinner proposed a formative model known as operant conditioning which proposes that we learn from our experience based on reward or punishment5. In short, if we like it, we learn to do it more; if we don’t like it, we learn to do it less. Many therapies that aim to promote skill development have foundations in Skinner’s operant conditioning model (e.g., applied behavior analysis). Whether a baby likes or feels rewarded, and then learns from the environment or activity, is related to a child’s sensory processing of and physiological response to, the activity or environment. Imagine, for example, an infant who upon seeing their mother’s face during peek-a-boo, experiences a pleasurable physiological response (or arousal); the infant is likely enjoying this and feels rewarded by the activity, is likely to engage more, and learn about this social interaction (reciprocal smiling, relationship between verbal and physical play interactions, etc). In short, our internal reward experience, including physiological arousal response, will influence what we engage with and learn from our environment.

The biology behind physiological arousal is complex. Many things happen when our body responds to stimuli in the environment. Relatively quick responses include dilation or constriction of the pupils. Other responses are changes in heart rate and breathing rate, quicker or slower depending on the saliency of the experience. Changes also occur at the neurobiological level when reacting to salient stimuli including changes in key neural chemicals (e.g., dopamine6) as well as activation of multiple, functionally connected brain regions (e.g., frontal cortex and subcortical structures such as the amygdala). While dissecting the neural circuitry of arousal in humans is complex and limited by technology, physiological markers of arousal can be ascertained relatively easily (e.g., pupillary, cardiac, and respiratory dynamics) and may be a homolog to underlying neural activity that can ultimately be tested in non-human models. There is evidence that physiological arousal has a key role in human psychology. For example, many therapies integrate autonomic nervous system regulation into treatment, mostly for anxiety and trauma-related disorders (e.g., biofeedback7–9), and psychopharmacology utilizes the downstream release or reuptake of neurotransmitters associated with arousal to regulate feelings of anxiety or depression10. Despite the acknowledged importance of arousal regulation, the dynamic nature of various physiological arousal phenomena makes it very difficult to measure arousal in naturalistic situations, despite the potential relevance to learning and adaptation systems.

In addition to anxiety and mood disorders, other psychiatric conditions have increasing awareness of arousal dysregulation as a core feature. The 2013 changes to the diagnostic criteria for autism spectrum disorder (ASD) include sensory aversions, perhaps akin to over-arousal, to the second symptom domain. It is possible that the early biological and neurobiological differences of infants with or at likelihood for developing a neurodevelopmental disorder, like ASD, may be associated with dysregulation of the arousal system. This dysregulation may be present very early in life (potentially even prior to birth) and lead to downstream deficits in social motivation and ultimately symptoms of ASD such as social communication impairments. There is evidence to support this theory. Parents of infants as young as six months of age report significant sensory arousal differences in those infants who go on to develop ASD11. These patterns of atypical arousal vary from over-reactivity, under-reactivity, or broad dysregulation across stimuli12. Researchers have also hypothesized that some of the core features of an ASD diagnosis (e.g., repetitive motor movements) may exist and persist due to dysregulated arousal and a child’s attempts to regulate arousal13. Interestingly, early symptoms of atypical arousal have been linked to later severity of ASD symptoms12, poorer social skills14, and lower communication abilities12. This evidence points to the critical role arousal plays in ASD.

Despite this evidence and an increasing interest in sensory reactivity amongst the ASD research community, much of the literature is constrained by an ability to acquire meaningful, objective metrics of arousal. Eye tracking studies have shown that time spent looking at the eyes is a feature of ASD and may reflect deficits in social motivation15–18 though the specificity and onset of these differences is less robust, and no study has linked these findings with arousal biometrics. Much of the literature on arousal to date has focused on parent or observational reports of infant or child behavior that is interpreted as over- or under-reactive to sensory stimuli, an inherently subjective method. Little research has examined physiological aspects of arousal such as temporal dynamics of pupillary changes, heart rate, and breathing rate. No research has integrated multiple metrics of arousal in infants nor those with or at high likelihood for ASD. Our research team combines the expertise of psychologists, neuroscientists, and engineers to design methods to fill these critical gaps in the field. We use existing methods to promote the field’s understanding of atypical arousal and its relationship with ASD diagnosis, functional outcomes, and patterns of learning. We are actively gathering arousal biometrics in infants at low and high likelihood for developing ASD (based on whether they have an older sibling with ASD).

In the context of ASD, many researchers and clinicians recognize that regulation of the arousal system is necessary to promote learning (e.g., Adapted Responsive Teaching13,19). Teaching parents to recognize signs of dysregulation in their infant and methods to provide support to assist in regulation provides an opportunity to promote more, sustained regulated states, and ultimately increasing times during which an infant is in an optimal learning state. At this point, interventions that consider arousal regulation rely on infant behavioral cues to indicate possible dysregulation (e.g., increase of stimming behaviors). Our work will advance the understanding of arousal to promote the use of its underlying physiology to help parents and clinicians aid in regulating difficult behaviors.

The use of arousal biometrics also has the potential to catalyze therapeutic developments and new mechanistic discoveries. Though we are in the initial stages of our work, the theoretical and practical foundations robustly support further examination of arousal as an influential component underlying neurodevelopmental disorders. We are eager to continue this groundbreaking work and to improve the lives of those with ASD and other NDDs.




  1. Duschinsky R. “Tabula Rasa” and Human Nature. Philosophy. 2012;87(342):509-529.
  2. Ohline SM, Abraham WC. Environmental enrichment effects on synaptic and cellular physiology of hippocampal neurons. Neuropharmacology. 2019;145(Pt A):3-12. doi:10.1016/j.neuropharm.2018.04.007
  3. De Giorgio A. The roles of motor activity and environmental enrichment in intellectual disability. Somatosens Mot Res. 2017;34(1):34-43. doi:10.1080/08990220.2016.1278204
  4. Bueno D. Genetics and Learning: How the Genes Influence Educational Attainment. Front Psychol. 2019;10(1622). doi:doi: 10.3389/fpsyg.2019.01622
  5. Gewirtz JL, Peláez-Nogueras M. B F Skinner’s legacy in human infant behavior and development. Am Psychol. 1992;47(11):1411-1422. doi:10.1037/0003-066X.47.11.1411
  6. Dichter GS, Rodriguez-Romaguera J. Anhedonia and Hyperhedonia in Autism and Related Neurodevelopmental Disorders. In: Pizzagalli DA, ed. Anhedonia: Preclinical, Translational, and Clinical Integration. Current Topics in Behavioral Neurosciences. Springer International Publishing; 2022:237-254. doi:10.1007/7854_2022_312
  7. Jerath R, Crawford MW, Barnes VA, Harden K. Self-Regulation of Breathing as a Primary Treatment for Anxiety. Appl Psychophysiol Biofeedback. 2015;40(2):107-115. doi:10.1007/s10484-015-9279-8
  8. Blase K, Vermetten E, Lehrer P, Gevirtz R. Neurophysiological Approach by Self-Control of Your Stress-Related Autonomic Nervous System with Depression, Stress and Anxiety Patients. Int J Environ Res Public Health. 2021;18(7):3329. doi:10.3390/ijerph18073329
  9. Manzoni GM, Pagnini F, Castelnuovo G, Molinari E. Relaxation training for anxiety: a ten-years systematic review with meta-analysis. BMC Psychiatry. 2008;8:41. doi:10.1186/1471-244X-8-41
  10. Murrough JW, Yaqubi S, Sayed S, Charney DS. Emerging Drugs for the Treatment of Anxiety. Expert Opin Emerg Drugs. 2015;20(3):393-406. doi:10.1517/14728214.2015.1049996
  11. Sacrey LAR, Zwaigenbaum L, Bryson S, et al. Can parents’ concerns predict autism spectrum disorder? A prospective study of high-risk siblings from 6 to 36 months of age. J Am Acad Child Adolesc Psychiatry. 2015;54(6):470-478. doi:10.1016/j.jaac.2015.03.014
  12. Grzadzinski R, Donovan K, Truong K, et al. Sensory Reactivity at 1 and 2 Years Old is Associated with ASD Severity During the Preschool Years. J Autism Dev Disord. 2020;50(11):3895-3904. doi:10.1007/s10803-020-04432-4
  13. Baranek GT, David FJ, Poe MD, Stone WL, Watson LR. Sensory Experiences Questionnaire: discriminating sensory features in young children with autism, developmental delays, and typical development. J Child Psychol Psychiatry. 2006;47(6):591-601. doi:10.1111/j.1469-7610.2005.01546.x
  14. Wagner JB, Luyster RJ, Tager-Flusberg H, Nelson CA. Greater Pupil Size in Response to Emotional Faces as an Early Marker of Social-Communicative Difficulties in Infants at High Risk for Autism. Infancy Off J Int Soc Infant Stud. 2016;21(5):560-581. doi:10.1111/infa.12128
  15. Nomi JS, Vij SG, Dajani DR, et al. Chronnectomic Patterns and Neural Flexibility Underlie Executive Function. NeuroImage. 2017;147:861-871. doi:10.1016/j.neuroimage.2016.10.026
  16. Jones W, Klin A. Attention to eyes is present but in decline in 2-6-month-old infants later diagnosed with autism. Nature. 2013;504(7480):427-431. doi:10.1038/nature12715
  17. Pelphrey KA, Sasson NJ, Reznick JS, Paul G, Goldman BD, Piven J. Visual scanning of faces in autism. J Autism Dev Disord. 2002;32(4):249-261. doi:10.1023/a:1016374617369
  18. Oruc I, Shafai F, Iarocci G. Link Between Facial Identity and Expression Abilities Suggestive of Origins of Face Impairments in Autism: Support for the Social-Motivation Hypothesis. Psychol Sci. 2018;29(11):1859-1867. doi:10.1177/0956797618795471
  19. Watson A, Timperio A, Brown H, Best K, Hesketh KD. Effect of classroom-based physical activity interventions on academic and physical activity outcomes: a systematic review and meta-analysis. Int J Behav Nutr Phys Act. 2017;14(1):114. doi:10.1186/s12966-017-0569-9