Background & Aims

Learning (e.g., acquisition and extinction of cue-pain associations) underlying upcoming aversive (pain) and appetitive events (pain relief) is crucial for humans and updating rules for both might be represented by similar and distinct patterns. Behavioral differences have been observed, as seen in faster aversive than appetitive acquisition but no differences in extinction. Neural underpinnings of these two types of learning have primarily been investigated, but using different sensory modalities (e.g., pain vs. monetary reward) limits interpretations of previous findings. The present study compares aversive and appetitive pain-related learning within the same sensory modality (heat pain increase vs. decrease) by employing a novel paradigm validated by a behavioral study with further elucidating the common and distinct neural mechanisms in this domain within healthy individuals.

Methods

N = 62 healthy individuals underwent an fMRI paradigm in which moderate continuous pain was elicited by a novel capsaicin-induced tonic heat pain model. Individually calibrated phasic pain (unconditioned stimulus, US) was paired with predictive cues (conditioned stimulus, CS). In the acquisition phase, three geometrical cues (CSincrease, CSdecrease, CSmedium) signaled pain exacerbation (USincrease), pain decrease (USdecrease) and no change in temperature (USmedium) respectively, whereas all cues were followed by USmedium in extinction. General linear model analyses were performed separately for each phase, with CS and US events as regressors of interest. To identify brain regions that show learning effects over time, we applied time modulation to CS regressors, and individual-wise contrasts modeling time x condition interactions (e.g., CSincrease x time > CSmedium x time) were entered into group-level one-sample t-tests. Functional connectivity analyses were performed using gPPI.

Results

Time x condition interaction indicated that compared to appetitive events, acquisition of aversive events was associated with a stronger increase in mediodorsal thalamus activity. Conjunction analysis revealed that both types of learning were accompanied by increasing responses in the medial occipital cortex.
Functional connectivity analysis using the occipital cortex as the seed region showed positive coupling with the frontal operculum during both conditions, suggesting a similar connectivity pattern regardless of valence during acquisition.
In the extinction phase, we found a greater decrease in activity in the lateral occipital cortex for aversive than appetitive condition, whereas the parahippocampal gyrus showed a stronger decrease in the appetitive condition. Both conditions showed a decrease in response over the course of the extinction phase in the vmPFC, which showed unspecific negative functional couplings with the periaqueductal gray (PAG) in both conditions.

Conclusions

Our results show that in healthy individuals, aversive and appetitive learning (within the pain modality) involve a common set of brain regions but can also be distinguished in areas such as the mediodorsal thalamus during acquisition and the occipital cortex, parahippocampal gyrus and vmPFC during extinction. In the brain network level, common connectivity patterns regardless of valence were found in both phases, including connectivity between the occipital cortex and frontal operculum during acquisition and the vmPFC-PAG coupling during extinction.

References

1 van der Schaaf, M.E., Schmidt, K., Kaur, J., Gamer, M., Wiech, K., Forkmann, K. and Bingel, U. (2022), Acquisition learning is stronger for aversive than appetitive events. Communications Biology, vol. 5, no. 1, pp. 1-10.
2 Fullana, M.A., Harrison, B.J., Soriano-Mas, C., Vervliet, B., Cardoner, N., Àvila-Parcet, A. and Radua, J. (2016), Neural signatures of human fear conditioning: an updated and extended meta-analysis of fMRI studies. Molecular Psychiatry, vol. 21, no. 4, pp. 500-508.
3 Klein, S., Kruse, O., León, I.T., Van Oudenhove, L., van’t Hof, S.R., Klucken, T., Wager, T.D. and Stark, R. (2022), Cross-paradigm integration shows a common neural basis for aversive and appetitive conditioning. NeuroImage, vol. 263, pp. 119594.
4 Martin-Soelch, C., Linthicum, J. and Ernst, M. (2007), Appetitive conditioning: neural bases and implications for psychopathology. Neuroscience & Biobehavioral Reviews, vol. 31, no. 3, pp. 426-440.
5 Forkmann, K., Wiech, K., Schmidt, K., Schmid-Köhler, J. and Bingel, U. (2023), Neural underpinnings of preferential pain learning and the modulatory role of fear. Cerebral Cortex, vol. 33, no. 16, pp. 9664-9676.
6 McLaren, D.G., Ries, M.L., Xu, G., Johnson, S.C. (2012), A generalized form of context dependent psychophysiological interactions (gPPI): a comparison to standard approaches. Neuroimage, vol. 61, no. 4, pp. 1277-1286.

Presenting Author

Jialin Li

Poster Authors

Jialin Li

MSc

Ruhr-Universität Bochum

Lead Author

E-mail

Topics

  • Pain Imaging