Resting-state functional heterogeneity of the right insula contributes to pain sensitivity

Previous studies have described the structure and function of the insular cortex in terms of spatially continuous gradients. Here we assess how spatial features of insular resting state functional organization correspond to individual pain sensitivity. From a previous multicenter study, we included 107 healthy participants, who underwent resting state functional MRI scans, T1-weighted scans and quantitative sensory testing on the left forearm. Thermal and mechanical pain thresholds were determined. Connectopic mapping, a technique using non-linear representations of functional organization was employed to describe functional connectivity gradients in both insulae. Partial coefficients of determination were calculated between trend surface model parameters summarizing spatial features of gradients, modal and modality-independent pain sensitivity. The dominant connectopy captured the previously reported posteroanterior shift in connectivity profiles. Spatial features of dominant connectopies in the right insula explained significant amounts of variance in thermal (R 2 = 0.076; p < 0.001 and R 2 = 0.031; p < 0.029) and composite pain sensitivity (R 2 = 0.072; p < 0.002). The left insular gradient was not significantly associated with pain thresholds. Our results highlight the functional relevance of gradient-like insular organization in pain processing. Considering individual variations in insular connectopy might contribute to understanding neural mechanisms behind pain and improve objective brain-based characterization of individual pain sensitivity.