Delineating a Pathway for the Discovery of Functional Connectome Biomarkers of Autism

The promise of individually tailored care for autism has driven efforts to establish biomarkers. This chapter appraises the state of precision-medicine research focused on biomarkers based on the functional brain connectome. This work is grounded on abundant evidence supporting the brain dysconnection model of autism and the advantages of resting-state functional MRI (R-fMRI) for studying the brain in vivo. After considering biomarker requirements of consistency and clinical relevance, we provide a scoping review of R-fMRI studies of individual prediction in autism. In the past 10 years, responding to the availability of open data through the Autism Brain Imaging Data Exchange, machine learning studies have surged. Nearly all have focused on diagnostic label classification. These efforts have shown that autism prediction is feasible using functional connectome markers, with accuracy reported well above chance. In parallel, emerging approaches more directly addressing autism heterogeneity are paving the way for much-needed biomarkers of longitudinal outcome and treatment response. We conclude with key challenges to be addressed by the next generation of studies.