Abstract
Numerous methods exist for quantifying statistical dependencies, termed "functional coupling" (FC), between regional brain activity recorded with resting-state functional magnetic resonance imaging (rs-fMRI). However, their efficacy in mitigating the effects of known sources of noise, such as those induced by participant head motion, and in augmenting effect sizes for brain-wide association studies (BWAS), remains unclear. Here we compared 10 different measures of FC, including correlations, partial correlations, coherence, mutual information, and partial information decomposition, and one measure of effective connectivity (EC; regression dynamic causal modeling), across two independent datasets comprising a total of 1,797 participants (867 males). Each method was evaluated for its ability to mitigate motion-related confounds in FC/EC estimates (assessed via framewise-displacement - edgewise FC correlations) and for its utility in predicting 94 behavioral measures (assessed via cross-validated kernel ridge regression). Our analyses showed that EC was most resistant to motion artifacts but had the weakest behavioral predictions. Conversely, traditional correlation-based methods showed the highest sensitivity to motion, but offered the strongest behavioral prediction across most domains and datasets. Nonetheless, relative differences in predictive accuracies were small, indicating that the use of different FC or EC metrics in rs-fMRI does not significantly impact BWAS effect sizes.