Domain-General Neural Effects of Associative Learning and Expectations on Pain and Hedonic Taste Perception

J Neurosci. 2026 Jan 21;46(3):e1103252025. doi: 10.1523/JNEUROSCI.1103-25.2025.

Abstract

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.

Keywords: anterior insula; associative learning; expectation; orbitofrontal cortex; pain; tastes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Anticipation, Psychological / physiology
  • Association Learning* / physiology
  • Brain Mapping
  • Brain* / physiology
  • Cues
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Pain Perception* / physiology
  • Pain* / physiopathology
  • Pain* / psychology
  • Taste Perception* / physiology
  • Young Adult