Time-varying phase synchronization of resting-state functional magnetic resonance imaging reveals a shift toward self-referential processes during sustained pain

Growing evidence has suggested that time-varying functional connectivity between different brain regions might underlie the dynamic experience of pain. This study used a novel, data-driven framework to characterize the dynamic interactions of large-scale brain networks during sustained pain by estimating recurrent patterns of phase-synchronization. Resting-state functional magnetic resonance imaging signals were collected from 50 healthy participants before (once) and after (twice) the onset of sustained pain that was induced by topical application of capsaicin cream. We first decoded the instantaneous phase of neural activity and then applied leading eigenvector dynamic analysis on the time-varying phase-synchronization. We identified 3 recurrent brain states that show distinctive phase-synchronization. The presence of state 1, characterized by phase-synchronization between the default mode network and auditory, visual, and sensorimotor networks, together with transitions towards this brain state, increased during sustained pain. These changes can account for the perceived pain intensity and reported unpleasantness induced by capsaicin application. In contrast, state 3, characterized by phase-synchronization between the cognitive control network and sensory networks, decreased after the onset of sustained pain. These results are indicative of a shift toward internally directed self-referential processes (state 1) and away from externally directed cognitive control processes (state 3) during sustained pain.