The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder

John D. Lewis, Alan C. Evans, John R. Pruett, Kelly N. Botteron, Robert C. McKinstry, Lonnie Zwaigenbaum, Annette Estes, D. Louis Collins, Penelope Kostopoulos, Guido Gerig, Stephen Dager, Sarah Paterson, Robert T. Schultz, Martin Styner, Heather Hazlett, Joseph Piven

    Research output: Contribution to journalArticle

    Abstract

    Background: Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. Methods: This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Results: Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. Conclusions: These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior.

    Original languageEnglish (US)
    JournalBiological Psychiatry
    DOIs
    StateAccepted/In press - Jul 22 2016

    Fingerprint

    Brain
    Social Behavior
    Age of Onset
    Autism Spectrum Disorder
    Research
    Neuropathology

    Keywords

    • Autism
    • Connectivity
    • Development
    • Efficiency
    • Infant siblings
    • Network analysis

    ASJC Scopus subject areas

    • Biological Psychiatry

    Cite this

    Lewis, J. D., Evans, A. C., Pruett, J. R., Botteron, K. N., McKinstry, R. C., Zwaigenbaum, L., ... Piven, J. (Accepted/In press). The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2017.03.006

    The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder. / Lewis, John D.; Evans, Alan C.; Pruett, John R.; Botteron, Kelly N.; McKinstry, Robert C.; Zwaigenbaum, Lonnie; Estes, Annette; Collins, D. Louis; Kostopoulos, Penelope; Gerig, Guido; Dager, Stephen; Paterson, Sarah; Schultz, Robert T.; Styner, Martin; Hazlett, Heather; Piven, Joseph.

    In: Biological Psychiatry, 22.07.2016.

    Research output: Contribution to journalArticle

    Lewis, JD, Evans, AC, Pruett, JR, Botteron, KN, McKinstry, RC, Zwaigenbaum, L, Estes, A, Collins, DL, Kostopoulos, P, Gerig, G, Dager, S, Paterson, S, Schultz, RT, Styner, M, Hazlett, H & Piven, J 2016, 'The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder', Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2017.03.006
    Lewis, John D. ; Evans, Alan C. ; Pruett, John R. ; Botteron, Kelly N. ; McKinstry, Robert C. ; Zwaigenbaum, Lonnie ; Estes, Annette ; Collins, D. Louis ; Kostopoulos, Penelope ; Gerig, Guido ; Dager, Stephen ; Paterson, Sarah ; Schultz, Robert T. ; Styner, Martin ; Hazlett, Heather ; Piven, Joseph. / The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder. In: Biological Psychiatry. 2016.
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    abstract = "Background: Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. Methods: This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Results: Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. Conclusions: These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior.",
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    AU - McKinstry, Robert C.

    AU - Zwaigenbaum, Lonnie

    AU - Estes, Annette

    AU - Collins, D. Louis

    AU - Kostopoulos, Penelope

    AU - Gerig, Guido

    AU - Dager, Stephen

    AU - Paterson, Sarah

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    AB - Background: Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. Methods: This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Results: Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. Conclusions: These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior.

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