Enhanced behavioural and neural sensitivity to punishments in chronic pain and fatigue

Chronic pain and fatigue in musculoskeletal disease contribute significantly to disability, and recent studies suggest an association with reduced motivation and excessive fear avoidance. In this behavioural neuroimaging study in chronic inflammatory arthritis participants and healthy controls, we aimed to identify the specific behavioral and neural changes associated pain and fatigue during reward and loss decision-making. Computational modeling of behaviour identified a parametric signature, characterized most notably by increased punishment sensitivity. This signature is distinct from patterns previously reported in psychiatric conditions and it aligns with predictions of mechanistic models of chronic pain such as the fear avoidance model. Neural activity associated with the punishment prediction error was enhanced in the right posterior insular cortex, putamen, pallidum, and dorsolateral prefrontal cortex. Functional network connectivity analysis showed that insula centrality correlated with subjective reports of fatigue and pain. Overall, the findings show that pain and fatigue in chronic pain relate to objective behavioural changes, and can be mapped to a specific pattern of activity in brain circuits of motivation and decision-making.