Estimation of Voxelwise Effective Connectivities: Applications to High Connectivity Sub-Regions within Hippocampal and within Corticostriatal Networks

Standard BOLD connectivity analyses depend on aggregating the signals of individual voxel within regions of interest (ROIs). In certain cases, this aggregation implies a loss of valuable functional and anatomical information about sub-regions of voxels that drive the ROI level connectivity. We describe a data-driven statistical search method that identifies the voxels that are chiefly responsible for exchanging signals between regions of interest that are known to be effectively connected. We apply the method to high-resolution resting state functional magnetic resonance imaging (rs-fMRI) data from medial temporal lobe regions of interest of a single healthy individual measured repeated times over a year and a half. The method successfully recovered densely connected voxels within larger ROIs of entorhinal cortex and hippocampus subfields consistent with the well-known medial temporal lobe structural connectivity. To assess the performance of our method in more common scanning protocols we apply it to resting state fMRI data of corticostriatal regions of interest for 50 healthy individuals. The method recovered densely connected voxels within the caudate nucleus and the putamen in good qualitative agreement with structural connectivity measurements. We describe related methods for estimation of effective connections at the voxel level that merit investigation.