A computational mechanism of cue-stimulus integration for pain in the brain.

The brain integrates information from pain-predictive cues and noxious inputs to construct the pain experience. Although previous studies have identified neural encodings of individual pain components, how they are integrated remains elusive. Here, using a cue-induced pain task, we examined temporal functional magnetic resonance imaging activities within the state space, where axes represent individual voxel activities. By analyzing the features of these activities at the large-scale network level, we demonstrated that overall brain networks preserve both cue and stimulus information in their respective subspaces within the state space. However, only higher-order brain networks, including limbic and default mode networks, could reconstruct the pattern of participants' reported pain by linear summation of subspace activities, providing evidence for the integration of cue and stimulus information. These results suggest a hierarchical organization of the brain for processing pain components and elucidate the mechanism for their integration underlying our pain perception.