Individual Resting-State Brain Networks Enabled by Massive Multivariate Conditional Mutual Information

Individual-level resting-state networks (RSNs) based on resting-state fMRI (rs-fMRI) are of great interest due to evidence that network dysfunction may underlie some diseases. Most current rs-fMRI analyses use linear correlation. Since correlation is a bivariate measure of association, it discards most of the information contained in the spatial variation of the thousands of hemodynamic signals within the voxels in a given brain region. Subject-specific functional RSNs using typical rs-fMRI data, are therefore dominated by indirect connections and loss of spatial information and can only deliver reliable connectivity after group averaging. While bivariate partial correlation can rule out indirect connections, it results in connectivity that is too sparse due to lack of sensitivity. We have developed a method that uses all the spatial variation information in a given parcel by employing a multivariate information-theoretic association measure based on canonical correlations. Our method, multivariate conditional mutual information (mvCMI) reliably constructs single-subject connectivity estimates showing mostly direct connections. Averaging across subjects is not needed. The method is applied to Human Connectome Project data and compared to diffusion MRI. The results are far superior to those obtained by correlation and partial correlation.