Bridgette L. Tonnsen - US grants

Understanding the early predictors of autism is essential to promoting earlier identification, diagnosis and treatment. Although aberrant visual attention is one of the earliest identified predictors of autism and may play an integral role in the socio-communicative deficits inherent in the disorder, the emergence of atypical attention in infancy is poorly understood. The present proposal seeks to characterize the development of aberrant attention in autism by integrating cognitive and developmental neuroscience methods within a multiple-group, prospective longitudinal design. Methods will include computerized attention orienting and visual preference paradigms integrated with concurrently-measured heart-defined sustained attention. Integrating behavioral and heart-defined measures will critically inform whether behavioral eye movement reflects underlying cognitive processes of stimulus response. Patterns of behavioral and biomarkers will be compared across high risk infant siblings of children with autism (ASIBS), high risk infants with fragile X syndrome (FXS), and low risk controls;thus informing the etiological specificity of early attention indicators, which is essential to informing early diagnostic and treatment efforts. Specifically, we aim to: (1) evaluate group differences in attention orienting (disengagement, facilitation) and visual preference (social/nonsocial, novel/familiar) between 6, 9, and 12 months of age (9 and 12 months in FXS), (2) compare behavioral performance on computerized attention paradigms to heart-defined sustained attention, and (3) evaluate the relationship between autistic outcomes at 24 months and these early behavioral and biomarkers of attention. Multilevel modeling will be used to analyze the patterns of attention across high risk groups, as well as the relationship between early attention and autistic outcomes. This study is innovative in that it is the first to apply concurrently-measured behavioral and heart-defined attention to the prospective surveillance of infant attention in autism, as well as to compare behavioral and biomarkers of attention across high risk ASIBS and infants with FXS.

PROJECT SUMMARY / ABSTRACT Despite affecting 1 in 68 United States children, the mechanisms and early course of autism spectrum disorder (ASD) are largely unknown, delaying initiation of interventions known to alter the course of behavioral and neural development. Current studies of ASD emergence largely focus on infant siblings of children with ASD (ASIBs) who exhibit 20 times higher ASD risk than children without a family history. As a complement to this approach, studying the emergence of ASD in high-risk neurogenetic syndromes informs: (1) the generalizability of behav- ioral ASD ?red flags? to non-ASIBs, given the majority of children with ASD do not have positive sibling histories, and (2) genetic and biological pathways subserving ASD features, facilitating mechanistically-sensitive treat- ments. However, syndromic ASD studies are rarely attempted in infants due to the high costs, travel demands, and logistical challenges of assessing low-incidence groups. Furthermore, existing telehealth methods that could circumvent these challenges are not compatible with experimental, laboratory-based methods (e.g. visual atten- tion tasks, psychophysiology) sensitive to ASD risk. This Mentored Patient-Oriented Research Career Develop- ment Award (K23) will prepare Dr. Tonnsen, a clinically trained psychologist with expertise in ASD emergence in syndromic infants, to address these barriers by establishing a novel, telehealth-based assessment framework for prodromal ASD surveillance. This project leverages the candidate?s current expertise in biobehavioral pre- dictors of ASD through additional mentored training in (1) new ASD risk domains outside of her current expertise (e.g. social communication, motor skills), (2) telehealth-based clinical research, (3) mechanisms and pathways of syndromic ASD, (4) psychometrics and measurement, and (5) program management, academic writing, and ethics. Primary mentors are experts in the measurement of developmental psychopathology (Don Lynam, Ph.D.), syndromic ASD and telehealth (Leonard Abbeduto, Ph.D.), and social communication development in infants (Amanda Seidl, Ph.D.). Additional training is provided by a national team of experts across both patient-oriented (e.g. clinical profiles, treatment trials, healthcare engineering) and basic (e.g. genetics, mouse models) domains. With the support of her mentorship team, Dr. Tonnsen will develop and validate a telehealth assessment battery of prodromal ASD risk in local infants with syndromic intellectual disability (Aim 1). She will then remotely apply the battery to a national longitudinal sample of infants with Angelman syndrome (50% ASD risk) and fragile X syndrome (25-60% ASD risk; Aim 2) to generate preliminary data and hypotheses for a subsequent R01. The proposed research is innovative because it represents a substantial departure from current methodological frameworks and participant samples for prospective ASD studies, laying the foundation for higher-powered, lower-cost, and wider-reaching studies of ASD emergence. Furthermore, the protected time, training, and data afforded by this project will crystallize Dr. Tonnsen?s path to independence as an interdisciplinary expert in re- mote surveillance of syndromic ASD in infants.