Functional plasticity of the olfactory network following functional septorhinoplasty in persistent COVID-19-related olfactory dysfunction: an fMRI study

Background: Persistent COVID-19-related olfactory dysfunction (C19OD) has a significant disease burden. The underlying pathology is unclear, both at the level of the olfactory epithelium, and the higher neural networks. Functional septorhinoplasty (fSRP) is a novel intervention aimed at restoring odorant airflow to the olfactory epithelium, demonstrating clinically meaningful olfactory improvements in persistent C19OD patients. In the same cohort, we investigated the functional plasticity within the primary and higher-order olfactory brain networks using task-based functional magnetic resonance imaging (fMRI) before and after fSRP. Methods: In a prospective cohort study, patients with persistent C19OD underwent psychophysical olfactory testing, nasal airflow measurements, and olfactory task-based fMRI at baseline and 6 months post-fSRP. Whole-brain fMRI data was analysed to evaluate changes in neural activation and their correlations with clinical parameters. Results were mapped to standardized anatomical and olfactory atlases. Findings: Eight participants completed pre- and post-operative fMRI assessments. At baseline, increased deactivation was seen in the left hippocampus, and increased activation in bilateral cerebellum. Task-based activation was positively correlated with nasal volume in the right thalamus, and left cerebellum lobule VI. Post-operatively, task-based deactivation was seen in the left cerebellum crus II. Reduced task-dependent activation post- compared to pre-operatively was seen in the bilateral insula. Increased activation post- compared to pre-operatively positively correlated with change in nasal airflow in the right orbitofrontal cortex (OFC), superior and middle frontal gyrus, and frontal pole (FP). Increased post- compared to pre-operative activation correlated negatively with change in olfactory scores in bilateral insula, and left FP. Interpretation: Persistent C19OD is characterized by widespread functional alterations across higher-order cortical regions, reflecting altered central olfactory processing. fSRP elicits significant neural plasticity within these higher-order olfactory areas. The findings support the mechanism that augmenting airflow to the olfactory cleft drives olfactory recovery through