Familiarity and Salience Interact to Shape Neural Processing of Odors

Olfactory perception is shaped not only by the physical properties of odorants but also by prior experience and perceptual prominence. Odor familiarity and salience are known to modulate neural responses; however, how these factors interact to shape odor processing in the human brain remains poorly understood. Using functional magnetic resonance imaging (fMRI), we investigated the combined effects of odor familiarity and perceptual salience on neural activation and brain–behavior relationships during olfactory perception. Sixty-three healthy young women participated in a 2 × 2 factorial fMRI experiment manipulating odor familiarity (familiar vs. unfamiliar) and salience (low vs. high). Odors were delivered birhinally using a computer-controlled olfactometer while participants passively perceived the stimuli and subsequently rated perceived odor intensity and odor-evoked memory intensity. Whole-brain analyses and region-of-interest approaches focused on canonical olfactory, limbic, and memory-related regions. All odor conditions elicited robust activation across primary olfactory, limbic, and associative cortices. Low-salience familiar odors preferentially engaged medial temporal and orbitofrontal regions, whereas low-salience unfamiliar odors recruited fronto-parietal and attentional networks, suggesting greater evaluative processing in the absence of established odor representations. High-salience odors, irrespective of familiarity, produced more widespread and bilateral activation patterns consistent with stronger bottom-up sensory drive. Critically, significant brain–behavior relationships emerged only for familiar odors presented at low salience, where subjective memory intensity was negatively correlated with parahippocampal activation, indicating greater reliance on memory-based representations under conditions of weak sensory input. These findings demonstrate that odor familiarity and salience interact nonlinearly to shape neural processing, identifying low-salience familiar odors as a distinct perceptual state in which top-down memory mechanisms exert a stronger influence on olfactory perception.