A mesocorticolimbic signature of pleasure in the human brain

Pleasure is a fundamental driver of human behavior, yet its neural basis remains largely unknown. Rodent studies highlight opioidergic neural circuits connecting the nucleus accumbens, ventral pallidum, insula, and orbitofrontal cortex as critical for the initiation and regulation of pleasure, and human neuroimaging studies exhibit some translational parity. However, whether activation observed across these regions reflects a common, generalizable code for pleasure driven by opioidergic mechanisms remains unclear. Here we use pattern recognition techniques to develop a human functional magnetic resonance imaging signature of mesocorticolimbic activity unique to states of pleasure. In independent validation tests, we find this signature has high sensitivity to pleasant tastes and positive affect evoked by humor. The signature is spatially coextensive with mu-opioid receptor gene expression, and its response is attenuated by the opioid antagonist naloxone. These findings provide evidence of a basis for pleasure derived from primary and secondary rewards in humans that is distributed across brain systems, and suggest that similar mechanisms underlie hedonic impact across mammalian species.