An empirical Bayes normalization method for connectivity metrics in resting state fMRI

Functional connectivity analysis using resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a powerful technique for investigating functional brain networks. The functional connectivity is often quantified by statistical metrics (e.g., Pearson correlation coefficient), which may be affected by many image acquisition and preprocessing steps such as the head motion correction and the global signal regression. The appropriate quantification of the connectivity metrics is essential for meaningful and reproducible scientific findings. We propose a novel empirical Bayes method to normalize the functional brain connectivity metrics on a posterior probability scale. Moreover, the normalization function maps the original connectivity metrics to values between zero and one, which is well-suited for the graph theory based network analysis and avoids the information loss due to the (negative value) hard thresholding step. We apply the normalization method to a simulation study and the simulation results show that our normalization method effectively improves the robustness and reliability of the quantification of brain functional connectivity and provides more powerful group difference (biomarkers) detection. We illustrate our method on an analysis of a rs-fMRI dataset from the Autism Brain Imaging Data Exchange (ABIDE) study.