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April 3rd, 2025

Version: 1

Department of Neurology, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, University Duisburg-Essen, Hufelandstr. 55

neuroscience

biorxiv

Common and distinct neural mechanisms of aversive and appetitive pain-related learning

Li, J.Open in Google Scholar•Schmidt, K.Open in Google Scholar•Busch, L.Open in Google Scholar•Forkmann, K.Open in Google Scholar•Spisak, T.Open in Google Scholar•Kaur, J.Open in Google Scholar•Schlitt-Nguyen, F.Open in Google Scholar•Wiech, K.Open in Google Scholar•Bingel, U.Open in Google Scholar

Appetitive and aversive conditioning are both fundamental to adaptive behaviour, yet there remains limited understanding of how they differ on the behavioural and neural level. We investigated the two processes during acquisition and extinction using functional magnetic resonance imaging and behavioural measures. In a within-subject differential conditioning paradigm (preregistration DRKS00027448), aversive learning was induced by pairing visual cues with a temperature increase (pain rise), while appetitive learning involved a temperature decrease (pain reduction). Valence and contingency ratings confirmed successful learning for both types of learning, though only the appetitive condition showed a return to baseline ratings during extinction, suggesting incomplete extinction in the aversive condition. On the neural level, both engaged the visual cortex during acquisition (with increased functional connectivity with the right frontal operculum) and the ventromedial prefrontal cortex (vmPFC) during extinction. However, aversive learning showed a stronger activation increase in the mediodorsal thalamus with heightened connectivity with the locus coeruleus during acquisition, as well as sustained parahippocampal activity during extinction. Moreover, incomplete extinction in the aversive condition (as indicated by contingency ratings) was associated with sustained activity in the visual cortex during pain anticipation. These results suggest that while appetitive and aversive learning share activation in regions involved in sensory processing (occipital lobe) and learning (vmPFC), aversive learning uniquely engages areas promoting rapid acquisition (mediodorsal thalamus and locus coeruleus) and cautious unlearning, in line with the notion of a \"better-safe-than-sorry\" strategy.

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