Novel machine learning approaches for improving the reproducibility and reliability of functional and effective connectivity from functional MRI

Objective. New measures of human brain connectivity are needed to address gaps in the existing measures and facilitate the study of brain function, cognitive capacity, and identify early markers of human disease. Traditional approaches to measure functional connectivity (FC) between pairs of brain regions in functional MRI, such as correlation and partial correlation, fail to capture nonlinear aspects in the regional associations. We propose a new machine learning based measure of FC ( ML.FC ) which efficiently captures linear and nonlinear aspects. Approach. To capture directed information flow between brain regions, effective connectivity (EC) metrics, including dynamic causal modeling and structural equation modeling have been used. However, these methods are impractical to compute across the many regions of the whole brain. Therefore, we propose two new EC measures. The first, a machine learning based measure of effective connectivity ( ML.EC ), measures nonlinear aspects across the entire brain. The second, Structurally Projected Granger Causality ( SP.GC ) adapts Granger Causal connectivity to efficiently characterize and regularize the whole brain EC connectome to respect underlying biological structural connectivity. The proposed measures are compared to traditional measures in terms of reproducibility and the ability to predict individual traits in order to demonstrate these measures' internal validity. We use four repeat scans of the same individuals from the Human Connectome Project and measure the ability of the measures to predict individual subject physiologic and cognitive traits. Main results. The proposed new FC measure of ML.FC attains high reproducibility (mean intra-subject R 2 of 0.44), while the proposed EC measure of SP.GC attains the highest predictive power (mean R 2 across prediction tasks of 0.66). Significance. The proposed methods are highly suitable for achieving high reproducibility and predictiveness and demonstrate their strong potential for future neuroimaging studies.