Rapid learning in response to pain is a crucial survival mechanism, relying on forming associations between cues in the environment and subsequent pain or injury. Existing evidence suggests that associations between conditioned stimuli (cues) and unconditioned aversive stimuli (such as pain) are learned faster than for appetitive stimuli that signal pain relief. In addition, when the link between a conditioned and unconditioned stimulus is broken (by unpairing them), the extinction of this learning effect is slower for aversive that appetitive stimuli, resulting in a flatter extinction slope. Understanding why extinction slopes are reduced for aversive stimuli is important for advancing theoretical models of learning, and for devising ways of increasing the slope (and thus facilitating extinction learning) could help develop more effective methods of pain relief, particularly in the treatment of chronic pain.

 

In the current programmatic submission, Busch et al. (2023) will undertake two Registered Reports to test whether a verbal instruction intervention that explicitly informs participants about contingency changes between conditioned and unconditioned stimuli facilitates extinction learning, especially for aversive (painful) stimuli, and how changes in extinction learning relate to neural biomarkers of functional connectivity. In the first Registered Report, they will initially seek to replicate previous findings including faster acquisition of aversive than appetitive conditioned stimuli as well as incomplete extinction of aversive conditioned stimuli without verbal instruction. They will then test how the instruction intervention alters extinction slopes and the completeness of extinction for appetitive and aversive stimuli, using a range of behavioral measures (expectancy and valence ratings) and physiological measures (pupillometry, skin conductance responses). To shed light on the neural correlates of these processes, in the second Registered Report the authors will use functional magnetic resonance imaging (fMRI) to ask firstly how acquisition and extinction of aversive and appetitive conditioned responses are related to resting state brain connectivity within a network that includes ventromedial prefrontal cortex, amygdala, and striatum, and secondly, whether the effectiveness of instruction on extinction learning is associated with differences in resting state connectivity across this network.

 

The Stage 1 manuscript was evaluated over two rounds of in-depth review. Based on detailed responses to the reviewers' comments, the recommender judged that the manuscript met the Stage 1 criteria and therefore awarded in-principle acceptance (IPA).

 

URL to the preregistered Stage 1 protocol: https://osf.io/cj75p (under temporary private embargo)
 
Level of bias control achieved: Level 6. No part of the data or evidence that will be used to answer the research question yet exists and no part will be generated until after IPA.
 
List of eligible PCI RR-friendly journals:
 

 

1. Busch, L., Wiech, K., Gamer, M., Knicses, B., Spisak, T., Schmidt, K., & Bingel, U. (2023). Modulatory effects of instructions on extinction efficacy in appetitive and aversive learning: A registered report. In principle acceptance of Version 3 by Peer Community in Registered Reports. https://osf.io/cj75p