A key challenge for clinical trials of autism spectrum disorder (ASD) is the lack of objective measures that are sensitive to changes in core features. In the current project, Eva Loth and Robert Leech will combine age-appropriate animated cartoons with cutting-edge artificial intelligence techniques to optimize and validate a set of novel tablet tests for assessing key social, emotional, motivational and cognitive processes implicated in the core symptoms of ASD.

In the first phase, the researchers will use Bayesian adaptive optimization to individually adjust task difficulty and surface features of tests, so the same or comparable versions can be used from 3 years of age to adulthood and across all intellectual ability levels. The data obtained from these tests will then be used to create individual cross-domain biobehavioral fingerprints.

In the second phase, Loth’s team will carry out a suite of validation studies to establish psychometric properties of the tablet tests (i.e., test-retest reliability, convergent validity, construct validity) and create normative ranges from 1,500 individuals (including approximately 100-150 with ASD).

The third phase will leverage this work with separately funded multicenter, multidisciplinary clinical studies from the AIMS-2-TRIALS project. This will enable the team to test the optimized and validated battery in 700 individuals with ASD and 500 typically developing participants (ages 3-35 years) to ascertain relationships to core and associated features of ASD. They will also test it in an additional cohort of 4,500 South African children who are part of AIMS-2-TRIALS, to assess specificity to ASD core symptoms (versus other social, emotional and behavioral problems). Lastly, they plan to assess ‘sensitivity to change’ in a ‘fast fail’ pharmacological treatment study.

Together, this project will deliver validated, mechanistically sensitive outcome measures of core ASD symptoms that are low-cost, easy to administer/analyze, and scalable and that can be realistically deployed in clinical trials within the next few years.