Gray matter cortical thickness predicts individual pain sensitivity: a multi-center machine learning approach

Pain sensitivity is known to considerably vary across individuals. While the variability in pain has been linked to structural neural correlates, it is still unclear how well these findings replicate in independent data and whether they are powerful enough to provide reliable pain sensitivity predictions on the individual level. In this study, we constructed a predictive model of pain sensitivity utilising structural MRI-based cortical thickness data from a multi-center dataset (3 centers, 131 healthy participants). Cross-validated estimates revealed a statistically significant and clinically relevant predictive performance (Pearson’s r = 0.36, p < 0.0005). The predictions were found to be specific to pain sensitivity and not biased towards potential confounding effects (e.g., anxiety, stress, depression, center-effects). Analysis of model coefficients suggests that the most robust cortical thickness predictors of pain sensitivity are the right rostral anterior cingulate gyrus, left parahippocampal gyrus and left temporal pole. Cortical thickness in these regions was negatively correlated to pain sensitivity. Our results can be considered as a proof-of-concept for the capacity of brain morphology to predict pain sensitivity, paving the way towards future multimodal brain-based biomarkers of pain. Highlights 1. We present a robust, brain structure-based multi-center predictive model for pain sensitivity. 2. Our model based on gray matter cortical thickness explains 13% of the variance in pain sensitivity and generalizes to out-of-center data. 3. The predictions are specific to pain sensitivity and not driven by potential confounders such as stress, depression, anxiety, and center-effects. 4. The most important predictors were rostral anterior cingulate cortex, parahippocampal gyrus and temporal pole, all negatively correlated with pain sensitivity. ### Competing Interest Statement The authors have declared no competing interest.