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

eLife, Vol. 11 (2022)

Keywords
Authors
  • Marieke Jepma
  • Department of Psychology, University of Amsterdam, Amsterdam, Netherlands; Department of Psychology, Leiden University, Leiden, Netherlands; Leiden Institute for Brain and Cognition, Leiden, Netherlands
  • Mathieu Roy
  • Department of Psychology, McGill University, Montreal, Canada; Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada
  • Kiran Ramlakhan
  • Department of Psychology, Leiden University, Leiden, Netherlands; Department of Research and Statistics, Municipality of Amsterdam, Amsterdam, Netherlands
  • Monique van Velzen
  • Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands
  • Albert Dahan
  • Department of Anesthesiology, Leiden University Medical Center, Leiden, Netherlands

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.

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