The future of disentangling the heterogeneity of autism with neuroimaging studies

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition. Over the past decade, a considerable number of approaches have been developed to identify potential neuroimaging-based biomarkers of ASD and have uncovered specific neural mechanisms underlying behaviors associated with ASD. However, the substantial heterogeneity among those diagnosed with ASD hinders the development of biomarkers. Disentangling the heterogeneity of ASD is pivotal to improve quality of life for individuals with ASD by facilitating early diagnosis and individualized interventions for those who need support. In this Review, we discuss recent advances in neuroimaging that have facilitated the characterization of the heterogeneity of this condition from three frameworks: neurosubtyping, dimensional models, and normative models. In addition, we discuss the challenges, possible solutions, and clinical utility of these three frameworks. We argue that several factors need to be considered when parsing heterogeneity using neuroimaging, including co-occurring conditions, neurodevelopment, heredity and environment, and multi-site and multi-modality data. We close with a discussion of future directions for achieving a better understanding of the neural mechanisms underlying neurodevelopmental heterogeneity and the future of precision medicine in ASD.