Estimating trial-wise modulation of functional connectivity using event-related fMRI

Understanding the neural basis of human cognition requires measuring not only localized brain activity but also how functional interactions between brain regions change in response to different cognitive demands. Event-related fMRI is an efficient design for linking trial-wise behavioral and computational variables to brain activity, but comparable methods for examining their effects on functional connectivity remain limited. Here, we develop beta-PPI (beta-series psychophysiological interaction), a method that leverages single-trial response estimates from even-related fMRI to quantify how trial-wise variables modulate functional connectivity. This task-based functional connectivity method provides a flexible approach for studying functional connectivity for event-related fMRI designs. We evaluated beta-PPI using comprehensive simulations across several experimental conditions and signal qualities. Beta-PPI can sensitively detect ground-truth effects and exhibited good parameter recovery. Compared with generalized psychophysiological interaction, beta-PPI achieved comparable performance across most conditions while demonstrating improved statistical power under lower signal-to-noise conditions. We further validated beta-PPI using empirical event-related fMRI data. Distinct trial-wise cognitive variables selectively modulated functional connectivity during their corresponding trial epochs, demonstrating the temporal specificity and flexibility of the approach. By testing how trial-wise variables modulate functional connectivity, beta-PPI extends task-based connectivity analysis to model-based fMRI and provides a common single-trial framework that could facilitate the integration of connectivity, activation, and representational analyses in event-related fMRI.