Domain-general neural effects of associative learning and expectations on pain and hedonic taste perception

Predictive cues significantly influence perception through associative learning. However, it is unknown whether circuits are conserved across domains. We investigated how associative learning influences perceived intensity and valence of pain and hedonic taste, and whether expectancy-based modulation varies by aversiveness or modality. Sixty participants (37 females, 23 males) were randomly assigned to receive either painful heat, unpleasant liquid saline, or pleasant liquid sucrose during fMRI scanning. Following conditioning, cues initially associated with low or high intensity outcomes were intermittently followed by stimuli calibrated to elicit medium intensity ratings. Learned cues modulated expectations and subjective outcomes similarly across domains. Consistent with this, the orbitofrontal cortex exhibited domain-general anticipatory activation. Cue effects on perceived intensity and valence were mediated by the left anterior insula and thalamus, respectively - regions closely overlapping those identified in prior studies of pain expectancy (Atlas et al., 2010). Pain specificity was evident when we measured variations in stimulus intensity, whether we used univariate or multivariate approaches, but there was minimal evidence of specificity by modality or aversiveness in cue effects on medium trials. These findings suggest that shared neural circuits mediate the effects of learned expectations on perception, linking pain with other areas of affective processing and perception across domains. Significance Statement Learned expectations shape how we perceive the world, but it remains unclear whether similar brain circuits mediate expectation effects across aversive and hedonic domains. Using single-trial fMRI, we show that predictive cues alter perceived intensity and valence of pain and both aversive and appetitive tastes through shared neural mechanisms. The orbitofrontal cortex, anterior insula, and thalamus supported the domain-general modulation, while pain-specific effects emerged primarily when actual stimulus intensity varied. These findings reveal that associative learning engages overlapping neural pathways to influence perception across different sensory and affective experiences, suggesting a unified framework for understanding how the brain constructs subjective experience from expectation.