Decoding the neural basis of olfactory dysfunction: a multimodal MRI study in CRS-OD

BACKGROUND: Chronic rhinosinusitis with olfactory dysfunction (CRS-OD) affects both peripheral and central olfactory pathways. Persistent olfactory loss may induce neuroplastic changes in brain regions involved in olfactory processing. We hypothesized that CRS-OD is associated with gray matter atrophy in olfactory-related regions, accompanied by alterations in global functional connectivity as a manifestation of compensatory or maladaptive reorganization. To test this, we performed voxel-based morphometry (VBM) to identify gray matter differences, followed by seed-based functional connectivity (FC) analysis using the altered regions. METHODOLOGY: We prospectively recruited 23 CRS-OD patients and 23 healthy controls (HCs). All patients presented with persistent olfactory dysfunction lasting 6 to 240 months. All participants underwent MRI scanning at the same time point. Olfactory function was assessed in CRS-OD patients using the Threshold-Discrimination-Identification (TDI) test, the Questionnaire of Olfactory Disorders (QOD), and the Olfactory-Evoked Cognitive Score (OECS). MRI analyses included VBM, FC, and olfactory bulb volume on DRIVen Equilibrium turbo spin echo (TSE) images. RESULTS: CRS-OD patients exhibited significantly reduced olfactory bulb (OB) volumes compared to HCs and gray matter atrophy in the inferior frontal orbital gyrus, parahippocampal gyrus, hippocampus, thalamus, and putamen. FC analysis revealed decreased connectivity in sensory-integration networks and increased FC in the superior occipital gyrus, suggesting compensatory reorganization. CONCLUSIONS: CRS-OD is characterized by OB atrophy, gray matter atrophy, and disrupted FC, reflecting both peripheral and central neural alterations. Multimodal MRI may provide new insights into CRS-OD pathophysiology, warranting further longitudinal studies.