Reproducible neuroimaging features for diagnosis of autism spectrum disorder with machine learning

Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD.