Different brain systems support learning from received and avoided pain during human pain-avoidance learning

eLife, vol. 11

Abstract

Both unexpected pain and unexpected pain absence can drive avoidance learning, but whether they do so via shared or separate neural and neurochemical systems is largely unknown. To address this issue, we combined an instrumental pain-avoidance learning task with computational modeling, functional magnetic resonance imaging (fMRI), and pharmacological manipulations of the dopaminergic (100 mg levodopa) and opioidergic (50 mg naltrexone) systems ( N = 83). Computational modeling provided evidence that untreated participants learned more from received than avoided pain. Our dopamine and opioid manipulations negated this learning asymmetry by selectively increasing learning rates for avoided pain. Furthermore, our fMRI analyses revealed that pain prediction errors were encoded in subcortical and limbic brain regions, whereas no-pain prediction errors were encoded in frontal and parietal cortical regions. However, we found no effects of our pharmacological manipulations on the neural encoding of prediction errors. Together, our results suggest that human pain-avoidance learning is supported by separate threat- and safety-learning systems, and that dopamine and endogenous opioids specifically regulate learning from successfully avoided pain.

Authors 5

1. Marieke Jepma Aachen Department of Psychology, Leiden University Leiden Institute for Brain and Cognition

   Leiden University · University of Amsterdam

   Affiliation as printed

   Department of Psychology, Leiden University

   Department of Psychology, University of Amsterdam

   Leiden Institute for Brain and Cognition

   Department of Psychology, Leiden University; Department of Psychology, University of Amsterdam; Leiden Institute for Brain and Cognition

2. Mathieu Roy

   McGill University

   Affiliation as printed

   Alan Edwards Centre for Research on Pain, McGill University

   Department of Psychology, McGill University

   Alan Edwards Centre for Research on Pain, McGill University; Department of Psychology, McGill University

3. Kiran Ramlakhan Aachen Department of Psychology, Leiden University

   Leiden University · Gemeente Amsterdam

   Affiliation as printed

   Department of Psychology, Leiden University

   Department of Research and Statistics, Municipality of Amsterdam

   Department of Psychology, Leiden University; Department of Research and Statistics, Municipality of Amsterdam

4. Monique van Velzen Aachen Department of Anesthesiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Anesthesiology, Leiden University Medical Center

5. Albert Dahan Aachen Department of Anesthesiology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Anesthesiology, Leiden University Medical Center