Large scale validation of an early-age eye-tracking biomarker of an autism spectrum disorder subtype

Abstract

Few clinically validated biomarkers of ASD exist which can rapidly, accurately, and objectively identify autism during the first years of life and be used to support optimized treatment outcomes and advances in precision medicine. As such, the goal of the present study was to leverage both simple and computationally-advanced approaches to validate an eye-tracking measure of social attention preference, the GeoPref Test, among 1,863 ASD, delayed, or typical toddlers (12–48 months) referred from the community or general population via a primary care universal screening program. Toddlers participated in diagnostic and psychometric evaluations and the GeoPref Test: a 1-min movie containing side-by-side dynamic social and geometric images. Following testing, diagnosis was denoted as ASD, ASD features, LD, GDD, Other, typical sibling of ASD proband, or typical. Relative to other diagnostic groups, ASD toddlers exhibited the highest levels of visual attention towards geometric images and those with especially high fixation levels exhibited poor clinical profiles. Using the 69% fixation threshold, the GeoPref Test had 98% specificity, 17% sensitivity, 81% PPV, and 65% NPV. Sensitivity increased to 33% when saccades were included, with comparable validity across sex, ethnicity, or race. The GeoPref Test was also highly reliable up to 24 months following the initial test. Finally, fixation levels among twins concordant for ASD were significantly correlated, indicating that GeoPref Test performance may be genetically driven. As the GeoPref Test yields few false positives (~ 2%) and is equally valid across demographic categories, the current findings highlight the ability of the GeoPref Test to rapidly and accurately detect autism before the 2nd birthday in a subset of children and serve as a biomarker for a unique ASD subtype in clinical trials.

Infrequent Intranasal Oxytocin Followed by Positive Social Interaction Improves Symptoms in Autistic Children: A Pilot Randomized Clinical Trial

“…As such, they adhere to general recommendations for using clinimetric criteria [60]. Children additionally completed two eye-tracking tasks which provide an objective assessment of social attention and can also discriminate between ASD and typically developing children [13,14,[55][56][57] (see online suppl. material).…”

“…Our two primary outcome measures were a gold-standard objective clinical measure (Autistic Diagnostic Observation Schedule-2; ADOS-2) [52] and the caregiver-based social responsivity scale-2 (SRS-2 total score) [53,54]. A number of secondary outcome measures were also taken including two eye-tracking paradigms as measures of social attention and sensitive to autistic symptoms [13,14,[55][56][57]. Associations between symptom improvements and increased peripheral concentrations of OXT, autism social subtype [58], and OXT receptor genotype [16,17] were also investigated.…”

Infrequent intranasal oxytocin followed by positive social interaction improves symptoms in autistic children: a pilot randomized clinical trial

“…The eye-tracking secondary outcome measures demonstrated improved social attention following OXT treatment and may prove to be useful objective measures in future ASD clinical trials, particularly the dynamic social versus geometric pattern paradigm, or 'GeoPref test,' which is increasingly established as an early autism biomarker [56][57][58]. Interestingly, while OXT increased the proportion of time viewing the eye-region of happy, angry and neutral faces, it decreased that towards the eyes of fearful faces and so effects in children may be expression dependent.…”

“…As such, they adhere to general recommendations for using clinimetric criteria [61]. Children additionally completed two eye-tracking tasks which provide an objective assessment of social attention and can also discriminate between ASD and typically developing children [13,14,[56][57][58] (see online supplementary information). Finally, the strain experienced by caregivers themselves was assessed using the Cargeiver strain questionnaire (CSQ) [65].…”

“…Our two primary outcome measures were a gold-standard objective clinical measure (Autistic Diagnostic Observation Schedule – 2; ADOS-2) [53] and the caregiver-based social responsivity scale-2 (SRS-2 total score) [54,55]. A number of secondary outcome measures were also taken including two eye-tracking paradigms as measures of social attention and sensitive to autistic symptoms [13,14,56-58]. Associations between symptom improvements and increased peripheral concentrations of OXT, autism social subtype [59] and OXT receptor genotype [16,17] were also investigated.…”