Orienting to face stimuli is a skill that emerges in the first year of life and that continues to develop over time. Failure to detect or respond to faces i one of the earliest hallmarks and predictors of autism spectrum disorder (ASD). Disruption in the early instantiation of the social brain networks results in lifelong social communication impairments in ASD. These social impairments in ASD are due, in part, to atypical eye gaze (findings from eye tracking studies) and abnormal neural activity when viewing faces (findings from electroencephalography (EEG) and magnetoencephalography (MEG) studies), with eye-gaze and face-sensitive neural measures considered potential ASD endophenotypes. Findings from these studies show that the brain changes associated with ASD precede clinical behavioral symptoms. Given a relatively late formal diagnosis around three years of age, interventions do not begin until significant early brain development is complete. So that interventions can start early there is a need for markers identifying individuals at risk for ASD. Although the above EEG/MEG endophenotypes are promising, our understanding is poor regarding how neural measures change as a function of development. To address this gap in the research, this K01 aims to examine the development of face-related neural processes in order to identify age-appropriate neural endophenotypes in young children with ASD. The proposed study is possible with the recent installation of a whole-head infant and young child MEG system at the Children's Hospital of Philadelphia (CHOP), and given a strong technical and clinical training environment at CHOP. MEG provides ideal brain measures in infants and young children due to minimal preparation time and given excellent temporal and good spatial resolution. For the K01 research project, a longitudinal design is employed to examine the maturation of the face-sensitive activity in fusiform face area and associated local and whole-brain neural networks in typically developing (TD) children aged six months to four-years-old (images of faces and houses passively viewed), with follow-up assessments every 12 months. Obtaining eye-tracking and MEG data from three and four-year-old children with ASD allows assessment of TD versus ASD differences in eye-gaze and face neural networks, and thus age-sensitive endophenotypes in children recently diagnosed with ASD. K01 findings will set the stage for a R01 examining eye tracking and neural activity in infants at-risk for ASD. K01 training will provide the tools and experience needed for K01 applicant Dr. Chen to become an independent developmental neuroscience researcher with a line or research focused on studying social cognition in infants and children with neurodevelopmental disorders. Training includes one-to-one mentorship (mentor Dr. Roberts and his team) in infant MEG as well as advanced digital signal processing. Clinical training at CHOP's Center of Autism Research (CAR) includes obtaining a better understanding of autism in infants and young children via work with developmental pediatrician K01 co-mentor Dr. Susan Levy, obtaining an in- depth theoretical background of ASD social processing impairments via mentorship from K01 advisor Dr. Roberts Schultz, and an understanding of ASD clinical and cognitive measures via observation, case conferences, and workshops with clinical psychologist K01 advisor Dr. Judith Miller. Training in developmental neuroscience is accomplished via classroom work and one-on-one mentorship with K01 consultant Dr. Hirsh- Pasek. Finally, training in eye-tracking is accomplished via classroom work and mentorship from K01 consultant Dr. Julia Stephen (experienced in eye tracking + MEG data collection and analyses). Building upon Dr. Chen's previous MEG experience and her growing experience in clinical imaging research, Dr. Chen is well poised to benefit from advanced clinical and technical training in order to develop a research program that uses brain imaging to understand the neurophysiological development of social cognition skills in TD infants and children as well as abnormalities in these processes in infants and children with ASD.

Public Health Relevance

Orienting to face stimuli is a skill that emerges in the first year of life, with failure to detect or respond to faces one of the earliest hallmarks and predictors of autism spectrum disorder (ASD). Social impairments in ASD are due, in part, to atypical eye-gaze and abnormal neural activity when viewing faces, with eye-gaze and face- sensitive neural measures considered potential ASD endophenotypes. Employing a longitudinal design, this K01 aims to identify age-appropriate social neural endophenotypes in typical developing infants and young children as well as young children with ASD via whole-head infant magnetoencephalography (MEG) and eye tracking, with analyses determining the developmental trajectories of local and whole-brain neural networks associated with face processing in typically developing children, and with this information leveraged to identify age-specific abnormalities in the neural processes associated with face processing impairments in young children with ASD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH108822-04
Application #
9547514
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Sarampote, Christopher S
Project Start
2015-09-15
Project End
2020-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Edgar, J Christopher; Fisk Iv, Charles L; Chen, Yu-Han et al. (2017) By our bootstraps: Comparing methods for measuring auditory 40 Hz steady-state neural activity. Psychophysiology 54:1110-1127