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, we aimed to identify the specific behavioural and neural changes associated with musculoskeletal pain and fatigue during reward and loss decision-making. Twenty-nine participants with chronic inflammatory arthritis and 28 healthy controls performed an instrumental learning task (four-armed bandit) during 3 T brain functional MRI. Computational analyses with reinforcement learning models were used to quantify the hidden variables involved in reward and loss decision-making, compare them across groups and, finally, relate them to brain activity. We found that participants with chronic pain had higher sensitivity to punishments and increased activity associated with the punishment prediction error in the right posterior insular cortex, putamen, pallidum and dorsolateral prefrontal cortex. Functional network connectivity analysis showed that insula centrality was correlated with subjective reports of fatigue and pain during the task. The findings of this exploratory study suggest that pain and fatigue in chronic pain relate to objective behavioural changes in loss decision-making, which can be mapped to a specific pattern of activity in brain circuits of motivation and decision-making. The proposed parametric signature, characterized most notably by increased punishment sensitivity, is distinct from patterns previously reported in psychiatric conditions and it aligns with predictions of the fear avoidance model of pain.