Respiratory Phase Orchestrates Human Olfactory Cortical Dynamics

Abstract

AO_SCPLOWBSTRACTC_SCPLOWOlfaction is fundamental to perception, memory, and emotion, yet the neural basis of human odor processing remains poorly understood. Here, we demonstrate that odor-evoked brain activity is organized by respiratory phase-not absolute time-revealing that natural breathing structures olfactory cortical dynamics. Using simultaneous nasal respiration and electroencephalography (EEG) recordings in 17 participants, we delivered naturalistic odors (peppermint, oregano, and grapefruit) synchronized to individual breathing cycles. Odor presentation elicited distinct, respiratory phase-locked event-related spectral perturbations (RPL-ERSPs) in frontal and temporal regions, emerging during the first breath after stimulus onset. The most discriminative neural signatures were theta-band activity during inhalation and alpha-band activity during exhalation, patterns that were obscured in traditional time-locked analyses due to natural variability in breath duration. Leave-one-subject-out cross-validation of RPL-ERSPs achieved reliable odor discrimination (peppermint: AUC = 0.78; oregano: AUC = 0.68; grapefruit: AUC = 0.61), establishing that phase-locked features generalize across individuals. To connect neural responses to perceptual experience without relying on precise odor naming--which is notoriously difficult and can be disproportionately impaired in some populations--we quantified odor recognition using free-response descriptions scored with a semantic-similarity approach. Behavioral recognition strength paralleled the neural decoding hierarchy across odors, establishing the perceptual validity of RPL-ERSPs. RPL-ERSPs also revealed rapid habituation, with decoding performance declining over repeated presentations, due to selective degradation of the most informative phase-locked features. Together, these findings establish respiratory rhythm as a temporal scaffold for human olfactory cortical processing, positioning RPL-ERSPs as a sensitive, task-free approach for assessing olfactory function. We provide an open-source, respiration-synchronized olfactometer design (<$500) to enable replication and broader adoption of this approach. 1 TeaserAligning brain activity to natural breathing unlocks objective neural markers of human smell perception.