Inference of functional connectivity from direct and indirect structural brain connections

We propose statistical inference based on the Least Absolute Shrinkage and Selective Operator (Lasso) regression as a framework to investigate the relationship between structural brain connectivity data (DTI) and functional connectivity data (fMRI). Regions of interest (ROIs) are obtained from an accurate atlas-based segmentation. We use direct structural connections to model indirect (higher-order) structural connectivity. Subsequently, we use Lasso to associate each functional connection with a subset of structural connections. Lasso offers the advantage of simultaneous dimensionality reduction and variable selection. We use a cohort of 22 subjects with both resting-state fMRI and DTI and we provide both qualitative and quantitative results based on leave-one-out cross validation. The results demonstrate that the performance of prediction is enhanced through the incorporation of indirect connections. In fact, the mean explained variance was improved from 54%6.53 to 58%4.31 when indirect connections of up to second order are added and the improvement in performance was statistically significant (p #60; 0.05).