Mixture discrimination training induces durable and generalizable olfactory learning independent of odorant structure and concentration.

Previously, we showed that adult human olfaction retains plasticity in the unilateral processing of molecular chirality (Feng and Zhou, 2019). Using a similar unilateral discrimination protocol across three experiments with human adults (n = 96; 1295 sessions), we now reveal distinct patterns of specificity, generalization, and persistence in olfactory learning, independent of adaptation or task difficulty. Training with binary odor mixtures at varying ratios consistently produced durable gains that transferred across nostrils and generalized to novel mixtures differing in both structure and perceptual quality. Conversely, training with odor enantiomers or concentration differences yielded neither transfer nor generalization, and concentration discrimination learning was short-lived. These results indicate that mixture configural quality is a distinct olfactory attribute from chirality or relative concentration, and that discrimination learning engages plasticity at different stages of olfactory processing depending on the task-relevant attribute. Moreover, they identify mixture discrimination training as a promising strategy for rehabilitating smell loss and cultivating olfactory expertise.