Autism spectrum disorder (ASD) is an etiologically and phenotypically heterogenous condition. While a growing proportion of people with ASD have been identified to have a neurodevelopmental genetic syndrome (NDGS), many ASD cases remain idiopathic. Thus, it is crucial that research continue to attempt to parse ASD heterogeneity to facilitate the development of individually-tailored treatment options.

The rationale for this project is that future idiopathic ASD (and NDGS) data platforms will need an efficient, online, multi-dimensional instrument that collects neurobehavioral domains relevant to functioning. Ideally, the tool will be applicable to the full range of ASD and NDGS presentations, can be collected repeatedly to enable sensitive temporal profiling and track change, and will be quick and easy for parents and people with ASD to complete.

While many subjective report and objective performance measures for ASD exist, they all have significant limitations, and none form a comprehensive co-normed battery useful for the full spectrum of the condition. Recently, to address this measurement gap, Thomas Frazier’s group developed a Neurobehavioral Evaluation Tool (NET) using gold-standard measure development principles that includes 11 webcam-collected participant performance measures (including eye gaze, social attention and facial expressions) and 11 informant-report survey scales. This work was supported by a SFARI Director Award. Preliminary data in a modest sample of people with ASD and NDGS suggests good reliability and validity for NET measures. However, it will be crucial to evaluate scalability and conduct a large-sample comprehensive psychometric evaluation of the NET before it can be broadly disseminated for research and clinical use.

The overarching aim of the current project is to evaluate the feasibility, scalability and psychometric properties of the NET in two large ASD cohorts. Specifically, 1,000 ASD-diagnosed children and adolescents (ages 3 to 17) will be recruited nationally from SPARK. A clinical cohort of 150 autistic individuals and 150 at-risk children and adolescents without ASD (ages 3 to 17) will also be recruited from the MetroHealth Medical Center Autism Assessment Clinic. In both cohorts, NET data will be collected at baseline, with a follow-up after one month (for test-retest reproducibility) and then at six months (for test-retest stability). An additional smaller cohort of 40 autistic children and 40 typically developing children (ages 3 to 8) will also be recruited to carefully evaluate the construct validity of NET measures in this most challenging age range.

Aim 1 of the project will evaluate the feasibility and scalability of NET performance measures. Aim 2 will estimate the reliability, construct validity and norms for each NET measure. Aim 3 will examine long-term stability and sensitivity to change for each NET measure. The project will also collect normative data from 200 typically developing children and adolescents, explore possible neurobehavioral sub-groups within ASD and examine longitudinal trajectories of neurobehavioral function in ASD cases.

If the project aims are achieved, the NET will be an efficient, reliable, valid, multi-modal instrument with co-normed measures, that, by virtue of online (at-home) administration, will decrease burdens on autistic children and their families, minimize the need for travel to expert centers and increase the temporal resolution and power of future longitudinal studies and clinical trials, with the potential for future use in clinical practice.