Establishing Specificity of Motor Imitation as a Biomarker for Autism Spectrum Disorder

The long term goals of these studies are to identify motor imitation as a biomarker of autism spectrum disorder (ASD) to both deepen understanding of brain and behavioral mechanisms for comorbid conditions and improve diagnosis with a cost-effective, objective, and reliable assessment method we developed. Although ASD is defined by core deficits in social-communicative functioning and restricted interests and repetitive behaviors, an ASD diagnosis is often accompanied by clear impairments in motor control and learning that present early and persist through childhood and into adulthood. Prominent among these ASD-associated motor impairments is difficulty imitating others’ actions (i.e., motor imitation). Imitation is crucial to social-communicative development, and impaired imitation has long been recognized as a likely contributor to the core difficulties in ASD. Crucially, while movement difficulties are associated with several developmental conditions that commonly co-occur with ASD, including attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID), current literature suggests that deficits in motor imitation may distinguish these overlapping conditions and capture variation relevant to underlying biology of ASD. Efforts to establish imitation as a biomarker of ASD have been hampered by a lack of objective, reliable assessment, with studies thus far applying labor intensive methods that require subjective assessment by highly trained researchers/clinicians. Our team has pioneered the development of an automated Computerized Assessment of Motor Imitation (CAMI) to quantify ASD-associated imitation deficits with better diagnostic discrimination ability than traditional methods. A remaining challenge in developing motor imitation as a phenotypic biomarker is to establish the specific neural mechanisms contributing to imitation deficits. Previous fMRI studies on motor imitation in ASD have shown mixed results, possibly due to the significant limitations in assessing naturalistic motor imitation in the fMRI scanning environment, where there are substantial constraints on motion. To address this challenge, our team develops high-density diffuse optical tomography (HD-DOT) that enables fMRI-comparable image quality in an open setting. Herein, we propose to establish the specificity of motor imitation impairments (Aim 1) as well as the brain mechanisms underlying such impairments (Aim 2) of ASD relative to ADHD and ID. Our proposed study, by integrating state-of-the-art methods for quantitative, objective motor imitation assessment and concurrent identification of ASD-specific underlying neural correlates, has substantial potential to profoundly improve predictive diagnostic utility over current subjective clinical assessments and thereby aid public health efforts to identify and support affected children. ASD-specific neurobehavioral biomarkers identified through our proposed CAMI and HD-DOT methods may advance clinical subtyping of ASD and opportunities for individualized treatment, refine monitoring response to intervention, and inform underlying neurobiological mechanisms. Project Number: 1R21MH140025-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Adam Eggebrecht | Institution: WASHINGTON UNIVERSITY, SAINT LOUIS, MO | Award Amount: $450,797 | Activity Code: R21 | Study Section: Child Psychopathology and Developmental Disabilities Study Section[CPDD] View on NIH RePORTER: https://reporter.nih.gov/project-details/11310610