Dissecting Salience Network Responsivity to Evoked Nociception and Pain: Model Free Analyses

Dissecting the responses of brain changes to acute nociceptive stimuli includes understanding networks that dynamically interact to produce the experience of pain. Among these networks the salience, default, sensory, and cognitive/central executive networks are known to interact in monitoring external stimuli, assigning salience and diverting activity from self-reflection (default mode) to cognitive integration and planning potential reaction to pain (executive). Several studies of acute evoked pain report a pattern of activity reflecting the involvement of these networks. However, it has also been proposed that much of the activity seems to reflect a response to the saliency of pain rather than pain/nociceptive processing itself. These results stem from the assumption that the evoked fMRI signal arises from a single, canonical hemodynamic response induced by the stimuli. Using a model-free analysis we demonstrate that the observed fMRI response has a complex, dynamic nature not captured by model-based analysis. We provide evidence that these and other networks have a distinct temporal response. Results presented here suggest that proper modeling and characterization of the brain response is fundamental for a correct interpretation of brain activity in response to phasic/evoked noxious stimuli.