Olfactory training with multisensory stimulation: neural insights into cross-modal integration

Olfactory training (OT) has emerged as a first-line non-pharmacological treatment for olfactory dysfunction. This study aimed to determine whether multisensory stimulation during OT improves olfactory recovery and to explore the underlying neurobiological mechanisms.

Individuals aged 18-80 years with post-viral or idiopathic olfactory dysfunction lasting for at least one month were recruited. Participants were allocated to either multisensory OT (MOT, odor-congruent video clips during OT) or conventional OT (COT) for three months. A subset of participants underwent resting-state fMRI at baseline and post-training to evaluate changes in olfactory network connectivity, using the piriform cortex and orbitofrontal cortex as the predefined seed regions. Statistical analyses were performed using repeated-measures ANOVA to evaluate changes over time and between groups.

Ninety-five patients (MOT=51, COT=44) were included. Significant improvements in odor discrimination and composite TDI scores were observed across participants without significant session x group interaction. In the MOT group, pre-post gains were observed in odor discrimination, identification, and TDI. In the MRI subgroup (MOT=21, COT=18), MOT was associated with reduced functional connectivity between the right orbitofrontal cortex and the superior occipital, superior temporal, and postcentral gyri.

MOT was associated with olfactory improvement over the training period. Although between-group differences were not statistically significant, exploratory neuroimaging findings suggest post-MOT functional reorganization between olfactory and visual, auditory, and somatosensory regions. Incorporating multisensory stimulation into OT warrants further investigation as a potential strategy for olfactory rehabilitation.