Searching for biomarkers and behavioral signs of early risk for neurodevelopmental disorders has emerged as an important line of clinical research in an effort to improve diagnosis and develop the most effective treatments and preventive interventions. In our current award period we identified several significant differences between infants at high familial risk for ASD (defined as having an older sibling with the disorder) and low risk control infants, including alterations in EEG, atypical lateralization for speech and faces, and reduced cortical connectivity all of which might serve as early risk markers. These differences were not only identified during the first year of life, their developmental trajectories were also atypical; a finding that appears to be a hallmark of risk for ASD. Our findings open up important questions about whether these risk markers extend to other infants later diagnosed with ASD, particularly infants from the general population, and whether they might also serve as risk markers for other related disorders, particularly language and social communication delay. In the next award period we address these questions by adding a new group of infants who fail a developmental screener (the CSBS) at 12 months. This group will be drawn from general pediatric practices, and will be compared to high-risk infant siblings and low risk controls on a battery of electrophysiological and behavioral measures that will be administered at 12-14 months, and again at 18, 24 and 36 months, at which time diagnostic outcomes will be evaluated. The project will address two specific aims. First, Do neural and behavioral risk markers (and their developmental trajectories) that distinguish infants at familial risk for ASD from low risk controls extend to infants at risk based on early behavioral differences detected on a 12-month screening instrument? We hypothesize that some risk markers will be shared across both high-risk groups, though for the screened group this may only hold for infants with clinical outcomes and show different developmental trajectories. Other risk markers may be unique to infants at familial risk.
Our second aim addresses the question: Do the developmental profiles of neural and behavioral risk markers we identify predict only to later diagnoses of ASD or do they extend to other non-ASD neurodevelopmental outcomes at 36 months, including language or social communication delay? We hypothesize that some of our risk markers will be shared across these non-ASD related (and overlapping) clinical outcomes, while others will be unique to ASD outcomes. As research progresses on identifying behavioral and neural markers in infants that are at risk for neurodevelopment disorders, it is critical that we extend our research beyond familial risk to the general population and to evaluate risk markers across several diagnostic outcomes. In this way our goal is to advance knowledge of the shared and unique mechanisms that can ultimately be the focus of more targeted interventions at a time when there is greatest plasticity and opportunity for preventing adverse outcomes.

Public Health Relevance

This project is designed to detect the earliest behavioral and brain risk markers for autism spectrum disorder and related language and social communication delays. The findings will have a major influence in developing novel approaches to early screening and diagnoses for these disorders. In turn, infants and toddlers identified as showing significant risk signs at much younger ages will be able to take advantage of early interventions that may prevent the onset of clinically significant symptoms or reduce the severity of the disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010290-07
Application #
9194399
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Cooper, Judith
Project Start
2009-07-01
Project End
2020-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Boston University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Levin, April R; Varcin, Kandice J; O'Leary, Heather M et al. (2017) EEG power at 3 months in infants at high familial risk for autism. J Neurodev Disord 9:34
Finch, Kayla H; Seery, Anne M; Talbott, Meagan R et al. (2017) Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder. J Neurodev Disord 9:4
Chenausky, Karen; Nelson 3rd, Charles; Tager-Flusberg, Helen (2017) Vocalization Rate and Consonant Production in Toddlers at High and Low Risk for Autism. J Speech Lang Hear Res 60:865-876
Finch, Kayla H; Tager-Flusberg, Helen; Nelson, Charles A (2017) Neural responses to linguistic stimuli in children with and without autism spectrum disorder. Eur J Neurosci :
Varcin, Kandice J; Nelson 3rd, Charles A (2016) A developmental neuroscience approach to the search for biomarkers in autism spectrum disorder. Curr Opin Neurol 29:123-9
Talbott, Meagan R; Nelson, Charles A; Tager-Flusberg, Helen (2016) Maternal Vocal Feedback to 9-Month-Old Infant Siblings of Children with ASD. Autism Res 9:460-70
Messinger, Daniel S; Young, Gregory S; Webb, Sara Jane et al. (2016) Commentary: sex difference differences? A reply to Constantino. Mol Autism 7:31
Wagner, Jennifer B; Luyster, Rhiannon J; Tager-Flusberg, Helen et al. (2016) Greater Pupil Size in Response to Emotional Faces as an Early Marker of Social-Communicative Difficulties in Infants at High Risk for Autism. Infancy 21:560-581
Tager-Flusberg, Helen (2016) Risk Factors Associated With Language in Autism Spectrum Disorder: Clues to Underlying Mechanisms. J Speech Lang Hear Res 59:143-54
Chenausky, Karen; Norton, Andrea; Tager-Flusberg, Helen et al. (2016) Auditory-Motor Mapping Training: Comparing the Effects of a Novel Speech Treatment to a Control Treatment for Minimally Verbal Children with Autism. PLoS One 11:e0164930

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