Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)

Study overview

Study Description: This pilot study investigates the mechanisms of parosmia, a qualitative olfactory dysfunction increasingly seen after COVID-19, by examining functional and structural brain changes and peripheral inflammation. Using neuroimaging and biochemical analysis, it aims to distinguish parosmia from other olfactory disorders and provide a foundation for future diagnostic and therapeutic approaches. Objectives: Primary objective: * Evaluate the feasibility, validity, and methodological framework for deep phenotyping of acquired chemosensory disorders. * Examine task-based functional connectivity patterns from the olfactory bulb to higher-order central processing regions across groups with varying olfactory symptoms. * Associate central findings with peripheral inflammatory patterns at the olfactory mucosa. Secondary Objective: -Investigate the differences and longitudinal changes in white matter microstructural integrity associated with the progression and recovery of olfactory dysfunctions across the recruited patient population. Tertiary objective: -Investigate the psychophysiological impacts of altered smell perception, with an emphasis on its negative effects on dietary habits and cognitive functions. Endpoints: Co-Primary Endpoints: To identify functional connectivity differences across subgroups, with focus on parosmia. The study hypothesizes that parosmia patients exhibit neuroinflammation at the olfactory bulb or in the amygdala and hippocampus, leading to distorted valence perception. Altered connectivity between primary and secondary olfactory cortices is expected, differing significantly from hyposmia and, to a lesser extent, anosmia. These connectivity changes are expected to correlate with variations in smell function to uncover disrupted neural pathways underlying parosmia. To identify local inflammatory signatures at the olfactory mucosa that are associated with chemosensory dysfunction and altered functional connectivity. Secondary Endpoints: To evaluate whether changes in functional connectivity are associated with structural alterations, specifically reduced axonal myelination between primary and secondary olfactory cortices (amygdala and hippocampus), in parosmia patients (along with their symptoms graph) compared to healthy controls and, to a lesser extent, anosmia patients. Longitudinal analysis will determine if these structural changes lead to higher-order neural degeneration or other significant brain alterations. Tertiary endpoints: To investigate whether regions with structural and functional differences correlate with the duration and severity of smell loss, and to assess the impact of prolonged smell dysfunction on psychological health, eating behaviors, and quality of life.

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Collaborators and Investigators

National Institute on Deafness and Other Communication Disorders (NIDCD),

Joshua M Levy, M.D., PRINCIPAL_INVESTIGATOR, National Institute on Deafness and Other Communication Disorders (NIDCD)

Study Record Dates

2029-10-14