The control of tonic pain by active 1 relief learning

15 Tonic pain after injury characterises a behavioural state that prioritises recovery. Although generally 16 suppressing cognition and attention, tonic pain needs to allow effective relief learning to reduce 17 the cause of the pain. Here, we describe a central learning circuit that supports learning of relief 18 and concurrently suppresses the level of ongoing pain. We used computational modelling of 19 behavioural, physiological and neuroimaging data in two experiments in which subjects learned to 20 terminate tonic pain in static and dynamic escape-learning paradigms. In both studies, we show 21 that active relief-seeking involves a reinforcement learning process manifest by error signals 22 observed in the dorsal putamen. Critically, this system uses an uncertainty (‘associability’) signal 23 detected in pregenual anterior cingulate cortex that both controls the relief learning rate, and 24 endogenously and parametrically modulates the level of tonic pain. The results define a 25 self-organising learning circuit that reduces ongoing pain when learning about potential relief. 26