The effect of global signal regression on DCM estimates of noise and effective connectivity from resting state fMRI

Abstract

The influence of the global BOLD signal on resting state functional connectivity in fMRI data remains a topic of debate, with little consensus. In this study, we assessed the effects of global signal regression (GSR) on effective connectivity within and between resting-state networks - as estimated with dynamic causal modelling (DCM) for resting state fMRI (rsfMRI). DCM incorporates a forward (generative) model that quantifies the contribution of different types of noise (including global measurement noise), effective connectivity, and (neuro)vascular processes to functional connectivity measurements. DCM analyses were applied to two different designs; namely, longitudinal and cross-sectional designs. In the modelling of longitudinal designs, we included four extensive longitudinal resting state fMRI datasets with a total number of 20 subjects. In the analysis of cross-sectional designs, we used rsfMRI data from 361 subjects from the Human Connectome Project. We hypothesized that (1) GSR would have no discernible impact on effective connectivity estimated with DCM, and (2) GSR would be reflected in the parameters representing global measurement noise. Additionally, we performed comparative analyses of the informative value of data with and without GSR. Our results showed negligible to small effects of GSR on connectivity within small (separately estimated) RSNs. For between-network connectivity, we found two important effects: the effect of GSR on between-network connectivity (averaged over all connections) was negligible to small, while the effect of GSR on individual connections was non-negligible. Contrary to our expectations, we found either no effect (in the longitudinal designs) or a non-specific (cross-sectional design) effect of GSR on parameters representing (global) measurement noise. Data without GSR were found to be more informative than data with GSR; however, in small resting state networks the precision of posterior estimates was greater using data after GSR. In conclusion, GSR is a minor concern in DCM studies; however, individual between-network connections (as opposed to average between-network connectivity) and noise parameters should be interpreted quantitatively with some caution. The Kullback-Leibler divergence of the posterior from the prior, together with the precision of posterior estimates, might offer a useful measure to assess the appropriateness of GSR, when nuancing data features in resting state fMRI.