Top-down threat bias in pain perception is predicted by higher segregation between resting-state networks

Top-down processes such as expectations have a strong influence on pain perception. Predicted threat of impending pain can affect perceived pain even more than the actual intensity of a noxious event. This type of threat bias in pain perception is associated with fear of pain and low pain tolerance, and hence the extent of bias varies between individuals. Large-scale patterns of functional brain connectivity are important for integrating expectations with sensory data. Greater integration is necessary for sensory integration; therefore, here we investigate the association between system segregation and top-down threat bias in healthy individuals. We show that top-down threat bias is predicted by less functional connectivity between resting-state networks. This effect was significant at a wide range of network thresholds and specifically in predefined parcellations of resting-state networks. Greater system segregation in brain networks also predicted higher anxiety and pain catastrophizing. These findings highlight the role of integration in brain networks in mediating threat bias in pain perception. Some individuals are more sensitive to threats of receiving strong pain stimuli. In this study, we report that higher system segregation in brain networks is associated with a greater threat bias (a reliance on expected intensity of pain versus the actual sensory stimuli in the manipulated pain experiment). We verified the results with different predefined resting-state parcellations at different network sparsities, and also tested subject-driven parcellations. These findings demonstrate that higher integration between resting-state networks is conducive for integrating top-down expectation processes with changes in bottom-up noxious stimulus intensities. Network segregation in resting state is thus associated with poor sensory integration and also shows association with anxiety and fear of pain.