Currently, parent report screening tools (e.g., M-CHAT, CSBS) are the only standardized screening options available to pediatricians for the early detection of autism. As demonstrated in our previous work (the 1-Year Well-Baby Check-Up Approach, Pierce et al., 2011), such screens have valuable strengths, but also weaknesses, including the impact of parent characteristics on how they rate their child's behavior and high false positive rates. Autism is a disorder that has its roots in abnormal early brain development, yet early identification rests largely in the hands of parent report measures, rather than in the domain of more objective, quantifiable behavior. To move beyond parent report as the only early screening choice, novel procedures for screening must be researched. During our last grant cycle we developed a novel eye-tracking test, the Geometric Preference Test for Autism (GeoPref Test). This simple one-minute test shows dynamic, colorful geometric moving patterns on half of a computer monitor and colorful active people on the other half. Of >440 toddlers tested using standard eye tracking technology, almost every toddler who fixated at high rates on the geometric patterns was ASD, and not typical or developmentally delayed. Thus, our laboratory experiments demonstrated exceptionally high, 99%, specificity of the GeoPref Test for detecting ASD. A low false positive rate is essential in a screening tool because false positives overload the system and create anxiety. Equally important in this heterogeneous disorder, the 1-min test identified 37% of all ASD toddlers. This is a larger percentage than any other early genetic, proteomic, neuroimaging or neurobehavioral screen, and it is fast, easy, and highly ASD specific.
Aim 1 will identify methods to integrate ASD specific test into clinical practice as a 2nd tier screen for babies who fail a routine 1st tier pencil and paper screen (i.e., the CSBS). Results will greatly improve the accuracy of early detection and speed referral of babies for diagnostic and treatment services. Using a portable eye tracker, 39 pediatricians will give the GeoPref Test in their office to toddlers who fail the CSBS who will in turn be referred to our Center for blinded diagnosis. This will be the first translation of an eye tracking finding on ASD into real-world clinical practice. In an effort to fully understand the clinical phenotype of ASD toddlers that """"""""fail"""""""" the GeoPref Test, Aim 2 will use novel experimental tests, such as a test of exploration, as well as standardized tests such as the Mullen, to identify clinical profiles tha distinguish these toddlers from others with an ASD. Although the GeoPref Test identifies a large subgroup of 37% of all ASD toddlers, equally fast, and accurate tests are needed to identify the remaining ASD toddlers.
Aim 3 proposes to develop new eye tracking tests, specifically novel social orienting and motherese paradigms, to detect these toddlers. Random forest classification algorithms will identify eye gaze signatures that best identify subgroups of ASD toddlers. All toddlers will receive a final blinded diagnosis at 30-36 months.

Public Health Relevance

In order to move beyond paper-and-pencil parent reports as the only option for early autism screening, novel techniques must be researched. Here, for the first time, this grant will translate an eye tracking test which was found to be highly accurate in detecting ASD - the GeoPref Test - out of the laboratory and into pediatric offices. Moreover, additional novel eye tracking tests will be developed and relationships between how a toddler performs on a given eye tracking test will be examined in relation to various clinical measures such as how a toddler explores their environment;understanding the clinical-eye tracking relationships is central to discovering the many unique subgroups that likely make up the overall ASD phenotype.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH080134-06A1
Application #
8579445
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Gilotty, Lisa
Project Start
2013-08-20
Project End
2018-05-31
Budget Start
2013-08-20
Budget End
2014-05-31
Support Year
6
Fiscal Year
2013
Total Cost
$387,500
Indirect Cost
$137,500
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Pierce, Karen; Marinero, Steven; Hazin, Roxana et al. (2016) Eye Tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an Autism Spectrum Disorder Subtype Associated With Increased Symptom Severity. Biol Psychiatry 79:657-66
Solso, Stephanie; Xu, Ronghui; Proudfoot, James et al. (2016) Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers. Biol Psychiatry 79:676-84
Lombardo, Michael V; Pierce, Karen; Eyler, Lisa T et al. (2015) Different functional neural substrates for good and poor language outcome in autism. Neuron 86:567-77
Pramparo, Tiziano; Lombardo, Michael V; Campbell, Kathleen et al. (2015) Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers. Mol Syst Biol 11:841
Pramparo, Tiziano; Pierce, Karen; Lombardo, Michael V et al. (2015) Prediction of autism by translation and immune/inflammation coexpressed genes in toddlers from pediatric community practices. JAMA Psychiatry 72:386-94
Bacon, Elizabeth C; Dufek, Sarah; Schreibman, Laura et al. (2014) Measuring outcome in an early intervention program for toddlers with autism spectrum disorder: use of a curriculum-based assessment. Autism Res Treat 2014:964704
Bakken, Trygve E (author list too long to display - see original citation for additional authors) (2012) Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans. Proc Natl Acad Sci U S A 109:3985-90
Torkamani, A; Schork, N J (2012) Background gene expression networks significantly enhance drug response prediction by transcriptional profiling. Pharmacogenomics J 12:446-52
Chow, Maggie L; Winn, Mary E; Li, Hai-Ri et al. (2012) Preprocessing and Quality Control Strategies for Illumina DASL Assay-Based Brain Gene Expression Studies with Semi-Degraded Samples. Front Genet 3:11
Glatt, Stephen J; Tsuang, Ming T; Winn, Mary et al. (2012) Blood-based gene expression signatures of infants and toddlers with autism. J Am Acad Child Adolesc Psychiatry 51:934-44.e2

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