Ranking brain areas encoding the perceived level of pain from fMRI data

Pain perception is thought to emerge from the integrated activity of a distributed brain system, but the relative contribution of the different network nodes is still incompletely understood. In the present functional magnetic resonance imaging (fMRI) study, we aimed to identify the more relevant brain regions to explain the time profile of the perceived pain intensity in healthy volunteers, during noxious chemical stimulation (ascorbic acid injection) of the left hand. To this end, we performed multi-way partial least squares regression of fMRI data from twenty-two a-priori defined brain regions of interest (ROI) in each hemisphere, to build a model that could efficiently reproduce the psychophysical pain profiles in the same individuals; moreover, we applied a novel three-way extension of the variable importance in projection (VIP) method to summarize each ROI contribution to the model. Brain regions showing the highest VIP scores included the bilateral mid-cingulate, anterior and posterior insular, and parietal operculum cortices, the contralateral paracentral lobule, bilateral putamen and ipsilateral medial thalamus. Most of these regions, with the exception of medial thalamus, were also identified by a statistical analysis on mean ROI beta values estimated using the time course of the psychophysical rating as a regressor at the voxel level. Our results provide the first rank-ordering of brain regions involved in coding the perceived level of pain. These findings in a model of acute prolonged pain confirm and extend previous data, suggesting that a bilateral array of cortical areas and subcortical structures is involved in pain perception.