Department of Psychology, University of Amsterdam, Amsterdam, Netherlands.
Department of Psychology, Leiden University, Leiden, Netherlands.
Elife. 2022 Jun 22;11:e74149. doi: 10.7554/eLife.74149.
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 ( = 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.
意外疼痛和意外无疼痛都可以驱动回避学习，但它们是否通过共享或单独的神经和神经化学系统来实现，在很大程度上尚不清楚。为了解决这个问题，我们将一种工具性的疼痛回避学习任务与计算建模、功能磁共振成像（fMRI）以及多巴胺能（100mg 左旋多巴）和阿片能（50mg 纳曲酮）系统的药物干预（n=83）相结合。计算建模提供的证据表明，未经治疗的参与者从接收到的疼痛中学习到的比避免的疼痛更多。我们的多巴胺和阿片类药物干预通过选择性地增加回避疼痛的学习率，否定了这种学习不对称性。此外，我们的 fMRI 分析表明，疼痛预测误差是在皮质下和边缘脑区进行编码的，而无疼痛预测误差是在额顶皮质区进行编码的。然而，我们没有发现我们的药物干预对预测误差的神经编码有任何影响。总的来说，我们的研究结果表明，人类的疼痛回避学习是由独立的威胁和安全学习系统支持的，而多巴胺和内源性阿片类物质则专门调节从成功回避的疼痛中学习。
