What is the best brain state to predict autistic traits?

Autism is a heterogeneous condition, and functional magnetic resonance imaging-based studies have advanced understanding of neurobiological correlates of autistic features. Little work has focused on the optimal brain states to reveal brain-phenotype relationships. Using connectome-based predictive modelling, we interrogated four datasets to determine scanning conditions that boost prediction of clinically relevant phenotypes and assess generalizability. In dataset one, a sample of youth with autism and neurotypical participants (n = 63), we found that a sustained attention task resulted in high prediction performance of autistic traits compared to a free-viewing social attention task and a resting-state condition. In dataset two (n = 25), we observed the predictive network model of autistic traits generated from the sustained attention task generalized to predict measures of attention in neurotypical adults. In datasets three and four, we determined the same predictive network model further generalized to predict measures of social responsiveness in the Autism Brain Imaging Data Exchange (n = 229) and the Healthy Brain Network (n = 643). Our data suggest an in-scanner sustained attention challenge can help delineate robust markers of autistic traits.