Translational Neuroimaging For Drug Discovery And Development In Autism Spectrum Disorders Guidance From Clinical Imaging And Preclinical Research

There is a profound unmet medical need for treatments that alleviate the core symptoms of autism spectrum disorders (ASDs). Drug discovery and development for ASDs is complicated by the highly heterogeneous genetics and behavioral phenotypes characteristic of ASDs, a poor understanding of ASD pathophysiology, and a lack of biomarkers. Translatable functional neuroimaging and electrophysiology techniques provide a means to delineate neural circuits and pathophysiology underlying ASDs, and may improve the medications development process by defining quantitative translational endpoints that align preclinical and clinical arenas. There is a lack of functional imaging research on responses to potential therapeutics in ASD patients and in animal models of ASD, but a rapidly growing body of research characterizing resting state and task-related neural circuit activation in ASD patients, and neurophysiology and behavioral phenotypes in ASD animal models, is providing valuable insight for building a neurocircuitry-based translational strategy to define patient populations and assess drug efficacy. The focus of this chapter is to review clinical neuroimaging research in ASDs and research in preclinical ASD models with an eye toward identifying neural circuits for use in translational ASD drug development strategies.