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Neural Precursors of Language in Infants at High Risk for Autism Spectrum Disorder Neural Precursors of Language in Infants at High Risk for Autism Spectrum Disorder The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Edwards, Laura Ann. 2015. Neural Precursors of Language in Infants at High Risk for Autism Spectrum Disorder. Doctoral dissertation, Harvard Graduate School of Education. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:23519638 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Neural Precursors of Language in Infants at High Risk for Autism Spectrum Disorder Laura Ann Edwards Tina A. Grotzer Charles A. Nelson Gigi Luk A Thesis Presented to the Faculty of the Graduate School of Education of Harvard University in Partial Fulfillment of the Requirements for the Degree of Doctor of Education 2015 ii © 2015 Laura Ann Edwards All Rights Reserved iii Acknowledgements This dissertation would not have been possible without the contributions of many, throughout my doctoral career. I would first and foremost like to thank the members of my ad hoc committee—Chuck Nelson, Tina Grotzer, and Gigi Luk. Chuck has been my day-to-day mentor since I arrived at Harvard. He has scaffolded my development as a researcher, enabling me to operate autonomously, while always being available to provide support and advice. I am indebted to him for his prompt and thoughtful attention to me, and his mentorship in my past, current, and future academic endeavors. Tina graciously took on the responsibility of being my academic advisor and dissertation committee chair midway through my doctoral career; I am grateful for her unwavering support of all facets of my work at Harvard, and for all the advice she has given me and the legwork she has done to make the process of producing this dissertation run so smoothly for me. Gigi is my hero for agreeing to serve on my committee on extremely short notice, and for providing prompt and enthusiastic feedback on my work at every stage thereafter. I would also like to thank Professor Jenny Thomson who is now on faculty at the University of Sheffield, UK, but who served as my academic advisor for my first few years at Harvard; Jenny was integral in helping me to chart a successful doctoral path, and in attending to both my academic and personal needs as a graduate student. Dr. Katherine Masyn, who is now on faculty in the School of iv Public Health at Georgia State University, provided me with individualized statistical training and support over the course of my doctoral study, and I am grateful to her for my confidence and comfort with statistical analysis. To my partner in doctoral studies and in life—Chris Buttimer—thank you for your attention, encouragement, praise, and support, in the many forms that they have taken over the years; you have contributed far more than I am able to get specific about here. Thanks as well to the other members of my doctoral program at Harvard, who have read, written, commiserated and in other ways helped me along this journey. None of the work I have done here would have been possible without past and present members of the Laboratories of Cognitive Neuroscience; thanks for collecting this data, sharing research insights and struggles with me, and supporting me daily, both inside and outside academia. Finally, thank you to all the families who participated in the Infant Sibling Project, from which this data originates; I am indebted to you for your dedication to scientific research. This work was funded, in part, by the Autism Speaks Dennis Weatherstone Predoctoral Fellowship, and a miRcore microgrant. v Table of Contents Dissertation Abstract.......................................................................................................... vi Chapter 1: General Introduction.......................................................................................... 1 References................................................................................................... 12 Chapter 2: Neural Correlates of Speech Perception in 3 Month Olds at Risk for ASD............................................................................................................. 18 Abstract ....................................................................................................... 18 Background ................................................................................................. 20 Materials and Methods................................................................................ 24 Results......................................................................................................... 34 Discussion ................................................................................................... 40 References................................................................................................... 53 Appendix 2.1............................................................................................... 59 Chapter 3: Neural Markers of Speech Perception in 3 Month Olds Predict Social and Communicative Outcomes at 18 Months ............................................. 63 Abstract ....................................................................................................... 63 Background ................................................................................................. 65 Materials and Methods................................................................................ 70 Results......................................................................................................... 78 Discussion ................................................................................................. 116 References................................................................................................. 125 Chapter 4: General Conclusions...................................................................................... 131 Curriculum Vita .............................................................................................................. 134 vi Neural Precursors of Language in Infants at High Risk for Autism Spectrum Disorder Abstract Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulties in social interaction and communication. Abnormal language development is a pervasive symptom of this disorder, though research has repeatedly shown that children with ASD who develop stronger language abilities have more positive outcomes. One strategy for improving the language, and thus life experiences, of children with ASD, is to get children at risk for the disorder into effective and appropriately targeted educational interventions in the very earliest stages of life, when precursors of language and other social behaviors are developing. However, ASD is currently not diagnosed until children have reached 2 or 3 years. In this dissertation, I investigate neural predictors of later language abilities, which may be measurable before behavioral precursors to language and ASD risk emerge. In my first study, I identify neural correlates of early language development in 3-month-old infant siblings of children with ASD, who are thus at high risk of developing the disorder. I find that whereas low-risk infants showed initial neural activation that decreased over exposure to repetition-based language stimuli, potentially indicating a habituation response to repetition in speech, infants at high risk for autism (HRA) showed no changes in their neural activity to these stimuli over exposure. These results suggest that putative precursors of vii language acquisition are disrupted in children at high risk for ASD as young as 3 months old. In my second study, I examine whether neural correlates of language development in 3-month-old infant siblings of children with ASD predict their 18- month social and communicative outcomes. These analyses revealed that neural activity to language stimuli in 3 month olds predicted expressive and receptive language, early gestures, sentence complexity, sentence length, and autism symptomatology in 18 month olds. In many cases, these associations differed for males and females, and for high and low risk children. The current research thus identifies early putative markers of language disability and ASD symptomatology, which, with future research and educational application, may aid in determining which children are most likely to benefit from placement into language-based educational intervention programs from the very first months of life. 1 Chapter 1 General Introduction Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulties in social interaction and communication. The most recent estimates from the Centers for Disease Control and Prevention (CDC) put the rate of ASD at 1 in 68 children in the United States (Baio, 2014). ASD occurs in all racial, ethnic and socioeconomic groups, though it is almost 5 times more prevalent in boys (in which the rate is 1 in 42) than in girls (who show a rate of 1 in 189; Baio, 2014)1. Children with ASD may have trouble reading social cues, understanding their own or others’ emotions, or adapting well to changes in their activities or routines. They have particular trouble learning from and about socially based information. Although ASD is, by definition, a group or
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