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Infant viewing of social scenes is under genetic control and is atypical in autism

Nature volume 547, pages 340344 (20 July 2017) | Download Citation

Abstract

Long before infants reach, crawl or walk, they explore the world by looking: they look to learn and to engage1, giving preferential attention to social stimuli, including faces2, face-like stimuli3 and biological motion4. This capacity—social visual engagement—shapes typical infant development from birth5 and is pathognomonically impaired in children affected by autism6. Here we show that variation in viewing of social scenes, including levels of preferential attention and the timing, direction and targeting of individual eye movements, is strongly influenced by genetic factors, with effects directly traceable to the active seeking of social information7. In a series of eye-tracking experiments conducted with 338 toddlers, including 166 epidemiologically ascertained twins (enrolled by representative sampling from the general population), 88 non-twins with autism and 84 singleton controls, we find high monozygotic twin–twin concordance (0.91) and relatively low dizygotic concordance (0.35). Moreover, the characteristics that are the most highly heritable, preferential attention to eye and mouth regions of the face, are also those that are differentially decreased in children with autism (χ2 = 64.03, P < 0.0001). These results implicate social visual engagement as a neurodevelopmental endophenotype not only for autism, but also for population-wide variation in social-information seeking8. In addition, these results reveal a means of human biological niche construction, with phenotypic differences emerging from the interaction of individual genotypes with early life experience7.

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References

  1. 1.

    Exploratory behavior in the development of perceiving, acting, and the acquiring of knowledge. Annu. Rev. Psychol. 39, 1–41 (1988)

  2. 2.

    , , & Face preference at birth. J. Exp. Psychol. Hum. Percept. Perform. 22, 892–903 (1996)

  3. 3.

    , & Visual following and pattern discrimination of face-like stimuli by newborn infants. Pediatrics 56, 544–549 (1975)

  4. 4.

    , & A predisposition for biological motion in the newborn baby. Proc. Natl Acad. Sci. USA 105, 809–813 (2008)

  5. 5.

    , , , & How face specialization emerges in the first months of life. Prog. Brain Res. 164, 169–185 (2007)

  6. 6.

    & Attention to eyes is present but in decline in 2–6-month-old infants later diagnosed with autism. Nature 504, 427–431 (2013)

  7. 7.

    & How people make their own environments: a theory of genotype > environment effects. Child Dev. 54, 424–435 (1983)

  8. 8.

    & Diagnosis of autism spectrum disorder: reconciling the syndrome, its diverse origins, and variation in expression. Lancet Neurol. 15, 279–291 (2016)

  9. 9.

    et al. Autism recurrence in half siblings: strong support for genetic mechanisms of transmission in ASD. Mol. Psychiat. 18, 137–138 (2013)

  10. 10.

    et al. Most genetic risk for autism resides with common variation. Nat. Genet. 46, 881–885 (2014)

  11. 11.

    et al. Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). Arch. Gen. Psychiatry 68, 1113–1121 (2011)

  12. 12.

    & Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurol. 14, 1109–1120 (2015)

  13. 13.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association, 2013)

  14. 14.

    , & Cognitive, language, social and behavioural outcomes in adults with autism spectrum disorders: a systematic review of longitudinal follow-up studies in adulthood. Clin. Psychol. Rev. 34, 73–86 (2014)

  15. 15.

    , & Inhibition of eye blinking reveals subjective perceptions of stimulus salience. Proc. Natl Acad. Sci. USA 108, 21270–21275 (2011)

  16. 16.

    , , , & Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism. Arch. Gen. Psychiatry 59, 809–816 (2002)

  17. 17.

    & Theories of associative learning in animals. Annu. Rev. Psychol. 52, 111–139 (2001)

  18. 18.

    Actions and habits: the development of behavioural autonomy. Phil. Trans. R. Soc. Lond. B 308, 67–78 (1985)

  19. 19.

    Permutation, Parametric, and Bootstrap Tests of Hypotheses (Springer, 2000)

  20. 20.

    , & Handbook of Child Psychology and Developmental Science Vol. 2 Cognitive Processes 7th edn (John Wiley & Sons, 2015)

  21. 21.

    & Forming inferences about some intraclass correlations coefficients. Psychol. Methods 1, 30–46 (1996)

  22. 22.

    Heritability: one word, three concepts. Biometrics 39, 465–477 (1983)

  23. 23.

    & The Neurology of Eye Movements (Oxford Univ. Press, 2006)

  24. 24.

    & Neural selection and control of visually guided eye movements. Annu. Rev. Neurosci. 22, 241–259 (1999)

  25. 25.

    Vision: A Computational Investigation into the Human Representation and Processing of Visual Information (W. H. Freeman, 1982)

  26. 26.

    Visual attention: the where, what, how and why of saliency. Curr. Opin. Neurobiol. 13, 428–432 (2003)

  27. 27.

    , & The neural mechanisms of top-down attentional control. Nat. Neurosci. 3, 284–291 (2000)

  28. 28.

    et al. Atypical Visual saliency in autism spectrum disorder quantified through model-based eye tracking. Neuron 88, 604–616 (2015)

  29. 29.

    Evolution’s Eye: A Systems View of the Biology–Culture Divide (Duke Univ. Press, 2000)

  30. 30.

    , , & The enactive mind, or from actions to cognition: lessons from autism. Phil. Trans. R. Soc. Lond. B 358, 345–360 (2003)

  31. 31.

    et al. Rapid video-referenced ratings of reciprocal social behavior in toddlers: a twin study. J. Child Psychol. Psychiatry 56, 1338–1346 (2015)

  32. 32.

    , , & Autism Diagnostic Observation Schedule (Western Psychological Services, 2002)

  33. 33.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 4th edn, text revision (American Psychiatric Association, 2004)

  34. 34.

    et al. Infant zygosity can be assigned by parental report questionnaire data. Twin Res. 3, 129–133 (2000)

  35. 35.

    & Rater bias in the EASI temperament scales: a twin study. J. Pers. Soc. Psychol. 56, 446–455 (1989)

  36. 36.

    , & Absence of preferential looking to the eyes of approaching adults predicts level of social disability in 2-year-old toddlers with autism spectrum disorder. Arch. Gen. Psychiatry 65, 946–954 (2008)

  37. 37.

    & Intraclass correlations: uses in assessing rater reliability. Psychol. Bull. 86, 420–428 (1979)

  38. 38.

    The Child’s Path to Spoken Language (Harvard Univ. Press, 1993)

  39. 39.

    & Approximate interval estimation for a certain intraclass correlation coefficient. Psychometrika 43, 259–262 (1978)

  40. 40.

    Negative values of the intraclass correlation coefficient are not theoretically possible. J. Clin. Epidemiol. 49, 1205–1206 (1996)

  41. 41.

    The eyes have it: the neuroethology, function and evolution of social gaze. Neurosci. Biobehav. Rev. 24, 581–604 (2000)

  42. 42.

    Color Appearance Models (John Wiley & Sons, 2005)

  43. 43.

    & A saliency-based search mechanism for overt and covert shifts of visual attention. Vision Res. 40, 1489–1506 (2000)

  44. 44.

    & Shifts in selective visual attention: towards the underlying neural circuitry. Hum. Neurobiol. 4, 219–227 (1985)

  45. 45.

    & Computational modelling of visual attention. Nat. Rev. Neurosci. 2, 194–203 (2001)

  46. 46.

    , & Modeling the role of salience in the allocation of overt visual attention. Vision Res. 42, 107–123 (2002)

  47. 47.

    & What attributes guide the deployment of visual attention and how do they do it? Nat. Rev. Neurosci. 5, 495–501 (2004)

  48. 48.

    et al. Modeling visual attention via selective tuning. Artif. Intell. 78, 507–545 (1995)

  49. 49.

    & On the distinction between visual salience and stimulus-driven attentional capture. J. Exp. Psychol. Hum. Percept. Perform. 25, 661–676 (1999)

  50. 50.

    & Goal-related activity in V4 during free viewing visual search. Evidence for a ventral stream visual salience map. Neuron 40, 1241–1250 (2003)

  51. 51.

    , , & in Eye Movements: A Window on Mind and Brain Ch. 25 (eds , , & ) 537–562 (Elsevier, 2007)

  52. 52.

    ., ., . & What the frog’s eye tells the frogs’s brain. Proc. Inst. Radio Engr. 47, 1940–1951 (1959)

  53. 53.

    & Primate brains in the wild: the sensory bases for social interactions. Nat. Rev. Neurosci. 5, 603–616 (2004)

  54. 54.

    , & Statistical analysis and functional interpretation of neuronal spike data. Annu. Rev. Physiol. 28, 493–522 (1966)

  55. 55.

    Randomization, Bootstrap, and Monte Carlo Methods in Biology (Chapman & Hall, 2006)

  56. 56.

    & Digital Signal Processing (Prentice-Hall, 1975)

  57. 57.

    , , & Frontal eye field projection to the paramedian pontine reticular formation traced with wheat germ agglutinin in the monkey. Brain Res. 329, 151–160 (1985)

  58. 58.

    & Interaction of the frontal eye field and superior colliculus for saccade generation. J. Neurophysiol. 85, 804–815 (2001)

  59. 59.

    & Physiology of the frontal eye fields. Trends Neurosci. 7, 436–441 (1984)

  60. 60.

    & Genetic structure of reciprocal social behavior. Am. J. Psychiatry 157, 2043–2045 (2000)

  61. 61.

    & Autistic traits in the general population: a twin study. Arch. Gen. Psychiatry 60, 524–530 (2003)

  62. 62.

    & Intergenerational transmission of subthreshold autistic traits in the general population. Biol. Psychiatry 57, 655–660 (2005)

  63. 63.

    et al. Developmental course of autistic social impairment in males. Dev. Psychopathol. 21, 127–138 (2009)

Download references

Acknowledgements

We thank the families and children for their participation. Research was supported by grants from the National Institute of Child Health & Human Development, HD068479 (J.N.C.) and U54 HD087011 (Intellectual and Developmental Disabilities Research Center at Washington University, J.N.C., principal investigator); and by the National Institute of Mental Health, MH100019 (N.M.) and MH100029 (A.K., W.J.). Additional support was provided by the Marcus Foundation, the Whitehead Foundation and the Georgia Research Alliance. Epidemiologic ascertainment of twins was made possible by the Missouri Family Register, a joint program of Washington University and the Missouri Department of Health and Senior Services; authorization to access was approved by the MO DHSS Institutional Review Board (S. Ayers, Chair) under auspices of the project entitled Early Quantitative Characterization of Reciprocal Social Behavior. We thank E. Mortenson, S. Sant, T. Gray, Y. Zhang, L. Campbell, L. Malik, A. Khan and E. McGarry for data collection and analysis; A. C. Heath and A. Agrawal for discussions of data analysis and statistics; C. Gunter for helpful comments on the manuscript; C. Drain and D. Hopper for project coordination and data collection; D. Jovanovic and R. Todorovic for contributions to twin family ascertainment; M. Panther for administrative support; and S. Kovar, J. Paredes, and M. Ly for designing and building the eye-tracking laboratory.

Author information

Affiliations

  1. Department of Psychiatry, Washington University, St Louis, Missouri 63110, USA

    • John N. Constantino
    • , Stefanie Kennon-McGill
    • , Claire Weichselbaum
    • , Natasha Marrus
    • , Alyzeh Haider
    •  & Anne L. Glowinski
  2. Department of Pediatrics, Washington University, St Louis, Missouri 63110, USA

    • John N. Constantino
  3. Intellectual and Developmental Disabilities Research Center, Washington University, St Louis, Missouri 63110, USA

    • John N. Constantino
    •  & Natasha Marrus
  4. Pediatric Biostatistics Core, Emory University School of Medicine, Atlanta, Georgia 30307, USA

    • Scott Gillespie
  5. Marcus Autism Center, Children’s Healthcare of Atlanta, Atlanta, Georgia 30329, USA

    • Cheryl Klaiman
    • , Ami Klin
    •  & Warren Jones
  6. Division of Autism & Related Disabilities, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30329, USA

    • Cheryl Klaiman
    • , Ami Klin
    •  & Warren Jones
  7. Center for Translational Social Neuroscience, Emory University, Atlanta, Georgia 30329, USA

    • Ami Klin
    •  & Warren Jones

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Contributions

J.N.C., A.L.G., A.K. and W.J. developed the initial idea and study design. J.N.C. and W.J. had full access to all data and take responsibility for data integrity and accuracy of analyses. J.N.C. supervised participant characterization. W.J. supervised technology development, data acquisition and analysis. S.K.-M., C.W., N.M. and A.H. collected data, ensured quality control at Washington University, conducted sub-analyses and participated in manuscript writing and revision. S.G., C.K. and W.J. performed data processing at Emory, ensured quality control across sites and participated in manuscript revision. W.J., A.K. and J.N.C. interpreted data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to John N. Constantino or Warren Jones.

Reviewer Information Nature thanks R. Adolphs, J. P. McCleery, C. Nelson and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Supplementary information

Videos

  1. 1.

    Data from one DZ twin pair watching an actress portraying the role of a caregiver engaging in dyadic interaction with the viewer (“Dyadic Mutual Gaze Video”)

    Videos show example eye-tracking data for twin pairs. In each video, crosshairs mark the point-of-regard and eye movements of each of the two twins, overlaid on top of the stimulus video. The video stimuli shown to children contained audio, although the data videos shown here do not include audio. The changing color of each crosshair over time signifies eye movement events: on-screen fixations to regions of interest (red, eyes; green, mouth; blue, body; yellow, object); saccades (white), blinks (black crosshair followed by black square in upper left corner of the video); and off-screen fixations (no crosshair, gray square in upper left corner of the video).

  2. 2.

    Data from one MZ twin pair watching an actress portraying the role of a caregiver engaging in dyadic interaction with the viewer (“Dyadic Mutual Gaze Video”).

    Videos show example eye-tracking data for twin pairs. In each video, crosshairs mark the point-of-regard and eye movements of each of the two twins, overlaid on top of the stimulus video. The video stimuli shown to children contained audio, although the data videos shown here do not include audio. The changing color of each crosshair over time signifies eye movement events: on-screen fixations to regions of interest (red, eyes; green, mouth; blue, body; yellow, object); saccades (white), blinks (black crosshair followed by black square in upper left corner of the video); and off-screen fixations (no crosshair, gray square in upper left corner of the video).

  3. 3.

    Data from one DZ twin pair watching scenes of children at play (“Triadic Peer Interaction Video”)

    Videos show example eye-tracking data for twin pairs. In each video, crosshairs mark the point-of-regard and eye movements of each of the two twins, overlaid on top of the stimulus video. The video stimuli shown to children contained audio, although the data videos shown here do not include audio. The changing color of each crosshair over time signifies eye movement events: on-screen fixations to regions of interest (red, eyes; green, mouth; blue, body; yellow, object); saccades (white), blinks (black crosshair followed by black square in upper left corner of the video); and off-screen fixations (no crosshair, gray square in upper left corner of the video).

  4. 4.

    Data from one MZ twin pair watching scenes of children at play (“Triadic Peer Interaction Video”)

    Videos show example eye-tracking data for twin pairs. In each video, crosshairs mark the point-of-regard and eye movements of each of the two twins, overlaid on top of the stimulus video. The video stimuli shown to children contained audio, although the data videos shown here do not include audio. The changing color of each crosshair over time signifies eye movement events: on-screen fixations to regions of interest (red, eyes; green, mouth; blue, body; yellow, object); saccades (white), blinks (black crosshair followed by black square in upper left corner of the video); and off-screen fixations (no crosshair, gray square in upper left corner of the video).

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https://doi.org/10.1038/nature22999

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