A comparison of statistical methods for detecting context-modulated functional connectivity in fMRI

Many cognitive and clinical neuroscience research studies seek to determine how contextual factors modulate cognitive processes. In fMRI, hypotheses about how context modulates distributed patterns of information processing are often tested by comparing functional connectivity between neural regions A and B as a function of task conditions X and Y, which is termed context-modulated functional connectivity (FC). There exist two exploratory statistical approaches to testing context-modulated FC: the beta-series method and psychophysiological interaction (PPI) analysis methods. While these approaches are commonly used, their relative power for detecting context-modulated FC is unknown, especially with respect to real-world experimental parameters (e.g., number of stimulus repetitions, inter-trial-interval, stimulus duration). Here, we use simulations to compare power for detecting context-modulated FC between the standard PPI formulation (sPPI), generalized PPI formulation (gPPI), and beta series methods. Simulation results demonstrate that gPPI and beta series methods are generally more powerful than sPPI. Whether gPPI or beta series methods performed more powerfully depended on experiment parameters: block designs favor the gPPI, whereas the beta series method was more powerful for designs with more trial repetitions and it also retained more power under conditions of hemodynamic response function variability. On a real dataset of adolescent girls, the PPI methods appeared to have greater sensitivity in detecting task-modulated FC when using a block design and the beta series method appeared to have greater sensitivity when using an event-related design with many trial repetitions. Implications of these performance results are discussed.