Decoding transcriptional signatures of the association between free water and macroscale organizations in healthy adolescents

We leveraged a novel index of diffusion MRI to investigate the relationships among cortical free water, macro-organizations and gene expression in healthy adults. Few research has been conducted to investigate the role of free water in the healthy adults due to it can easily be affected also by aging diseases. High quality data of 350 subjects from Human Connectome Project were used in our study. Cortical free water was estimated by using a bi-tensor model. The free water was high in the limbic, insular and somatosensory cortex, while being lower in motor and association cortex. The negative correlation between the free water and cortical thickness has been consistently identified in almost all the cortical regions. Negative correlation between the cortical free water and structural covariance (rho=-0.38, p_spin=0.005) revealed the free water was sensitive to cortical heterogeneity. Using human gene expression dataset, we found the gene expression pattern of the relationship between the free water and cortical thickness spatially coupled with primary gradient of structural covariance network (rho=0.40, p_spin=0.004). Our findings indicated the free water was sensitive to the cortical cellular status. The relationship between free water and macroscale organization also reflected hierarchal structures of cerebral cortex.