The pleasure of absent danger: Subjective, physiological and neural correlates of threat omission relief

We feel relieved when an expected threat stays away. These feelings of relief are important as they signal that the current situation turned out to be better-than-expected. In the context of fear, feelings of relief upon the absence of danger seem to correlate with the theoretical prediction error (PE) driving the learning of safety. Accordingly, recent neuroscientific evidence has demonstrated that there are vast similarities between the neural circuitry underlying the threat omission PE and the well-established reward PE. But how aversive expectations transform “nothing” into pleasurable events is not entirely clear yet.

We propose that the mu-opioid receptor (MOR) system may be a prime candidate to play the part, because of its dual role in mitigating pain and producing pleasure. Specifically, we postulate that in the context of perceived threat, endogenous opioids are released in order to mitigate impending pain. However, if the threat stays away, these pre-emptively released opioids may instead assign the rewarding value to the relief, which in turn will engage the reward system for safety learning.

In this dissertation, we aimed to provide a detailed analysis of threat omission relief in humans, by assessing how it is modulated by aversive expectations; endogenous opioidergic activity; and differences in anxiety-, depression- and reward-related traits. To this end, we combined a new experimental task with neuroimaging and pharmacological manipulations.

Because we propose a key role for expectations, we first developed and validated the Expectancy Violation Assessment (EVA) task, in which we parametrically manipulate probability and intensity-related expectations on a trial-by-trial basis. In chapter 2, we validated this task and showed that self-reported relief-pleasantness and omission-related skin conductance responses effectively tracked violations of expectancy at threat omission, in line with a PE signal. In the next chapter (chapter 3), we applied the EVA task in an fMRI context and confirmed that the unexpected omission of threat likewise triggered PE-like activations in key regions of the reward and salience circuit that furthermore correlated with the pleasantness of the reported relief. In chapter 4, we zoomed in on the proposed role of the MOR system in assigning the pleasurable reward-value to the threat omission. By blocking MOR with naltrexone, we showed that the pleasantness of the relief, but not omission-related SCR or brain responses were partially dependent on opioid signaling. Finally, in chapter 5, we pooled results across studies in order to explore how anxiety-, depression- and reward-related personality traits were related to the reported relief. In line with previous studies, we found that anxiety-prone individuals report higher levels of relief following omissions of weak stimulations, whereas depression-prone participants reported lower levels of relief pleasantness following omissions of stronger stimulations.