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.
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.
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|Eyler, Lisa T; Pierce, Karen; Courchesne, Eric (2012) A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism. Brain 135:949-60|
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|Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie (2011) Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res 1380:138-45|
|Pierce, Karen; Conant, David; Hazin, Roxana et al. (2011) Preference for geometric patterns early in life as a risk factor for autism. Arch Gen Psychiatry 68:101-9|
|Pierce, Karen; Carter, Cindy; Weinfeld, Melanie et al. (2011) Detecting, studying, and treating autism early: the one-year well-baby check-up approach. J Pediatr 159:458-465.e1-6|
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|Dinstein, Ilan; Pierce, Karen; Eyler, Lisa et al. (2011) Disrupted neural synchronization in toddlers with autism. Neuron 70:1218-25|
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|Pierce, Karen (2011) Early functional brain development in autism and the promise of sleep fMRI. Brain Res 1380:162-74|
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