Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain...

There is considerable interest in understanding the developmental origins and health implications of individual differences in brain structure and function. In this pre-registered study we demonstrate that a hidden subgroup within the general population-people with synesthesia (e.g. who "hear" colors)-show a distinctive behavioral phenotype and wide-ranging differences in brain structure and function. We assess the performance of 13 different brain-based biomarkers (structural and functional MRI) for classifying synesthetes against general population samples, using machine learning models. The features in these models were derived from subject-specific parcellations of the cortex using the Human Connectome Project approach. All biomarkers performed above chance with intracortical myelin being a particularly strong predictor that has not been implicated in synesthesia before. Resting state data show widespread changes in the functional connectome (including less hub-based connectivity). These brain-based individual differences within the neurotypical population can be as large as those that differentiate neurotypical from clinical brain states.