Synesthesia is linked to large and extensive differences in brain structure and function as determined by whole-brain biomarkers derived from the HCP (Human Connectome Project) cortical parcellation approach.

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.