Measuring Granger Causality between Cortical Regions from Voxelwise fMRI BOLD Signals with LASSO

Functional brain network studies using the Blood Oxygen-Level Dependent (BOLD) signal from functional Magnetic Resonance Imaging (fMRI) are becoming increasingly prevalent in research on the neural basis of human cognition. An important problem in functional brain network analysis is to understand directed functional interactions between brain regions during cognitive performance. This problem has important implications for understanding top-down influences from frontal and parietal control regions to visual occipital cortex in visuospatial attention, the goal motivating the present study. A common approach to measuring directed functional interactions between two brain regions is to first create nodal signals by averaging the BOLD signals of all the voxels in each region, and to then measure directed functional interactions between the nodal signals. Another approach, that avoids averaging, is to measure directed functional interactions between all pairwise combinations of voxels in the two regions. Here we employ an alternative approach that avoids the drawbacks of both averaging and pairwise voxel measures. In this approach, we first use the Least Absolute Shrinkage Selection Operator (LASSO) to pre-select voxels for analysis, then compute a Multivariate Vector AutoRegressive (MVAR) model from the time series of the selected voxels, and finally compute summary Granger Causality (GC) statistics from the model to represent directed interregional interactions. We demonstrate the effectiveness of this approach on both simulated and empirical fMRI data. We also show that averaging regional BOLD activity to create a nodal signal may lead to biased GC estimation of directed interregional interactions. The approach presented here makes it feasible to compute GC between brain regions without the need for averaging. Our results suggest that in the analysis of functional brain networks, careful consideration must be given to the way that network nodes and edges are defined because those definitions may have important implications for the validity of the analysis. Author Summary: Modern cognitive neuroscience views cognition in terms of brain network function. A network is a physical system of nodes connected to each other by edges. From the network perspective, cognitive function depends on activity patterns involving the nodes and edges of functional brain networks. It is important then, to appropriately define the nodes and edges of functional brain networks in order to understand cognition. In this study we consider the nodes of functional brain networks to be brain regions, and demonstrate a method that effectively measures the edge pattern between regions with a technique called Granger Causality. Our method is made possible by the utilization of recent advances from the field of statistics. Our approach is generally applicable to functional brain network analysis and contributes to the understanding of network properties of the brain.