Towards Experimental Approaches to Advance Discovery of Clinically Meaningful Sensory-Motor Biomarkers

Atypical motor function is a highly prevalent clinical feature of autism spectrum disorder (ASD). Differences in motor function both persist across the lifespan and scale linearly with the magnitude of core ASD symptom presentation. Because motor differences may be apparent earlier than core autism features, objective, quantifiable measures of motor function may help clinicians with early detection of neurodevelopmental delays/deviance, early diagnosis of ASD, and later differential diagnosis. Moreover, nuanced motor biomarkers represent a promising approach to parse presumed mechanistic heterogeneity across the autism spectrum, particularly as it relates to guiding precision intervention. To achieve these mechanistic-science and biomarker-development goals, we propose approaches to transcend limitations we see within the corpus of autism motor research as a whole. First, we suggest more transdiagnostic research to establish the specificity of particular motor behaviors for autism (vs. other neurodevelopmental conditions that also show motor atypicalities). Relatedly, enhancing the specificity of both motor constructs and core-symptom constructs (social-communicative, restricted and repetitive behaviors/interests [RRB]) within autism sensory-motor research will be essential for parsing the heterogeneity within the autism spectrum. Finally, in order to sharpen our mechanistic understanding, we recommend experimental designs that simultaneously and competitively test multiple cognitive-motor theories of autism within frameworks of Computational Motor Control and Bayesian Inference, as this approach will aid in developing clinically meaningful objective motor biomarkers based on mechanism. Each of the cognitive-motor theories we discuss in the chapter (hypo-priors, hyper-priors, prediction, inter-sensory bias, and sensory-motor transformation) ascribes different features of autism to different mechanisms; we recognize that different mechanisms may be at play across individuals within the heterogeneous autism spectrum in a way that accounts for both motor and non-motor heterogeneity. Finally, we discuss neuroanatomical correlates that may underpin each theory proposed, providing a brain-behavioral link between the early emerging “lower-level” features of autism (i.e., motor differences and low-order RRBs) and developmentally later emerging higher-level ASD symptomology (i.e., social communication differences and high-level RRBs).