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Original Investigation
March 18, 2021

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
  • 2Statistics Editor, JAMA Otolaryngology—Head and Neck Surgery
  • 3Department of Otolaryngology–Head and Neck Surgery, St Louis University School of Medicine, St Louis, Missouri
  • 4Editor, JAMA Otolaryngology—Head and Neck Surgery
JAMA Otolaryngol Head Neck Surg. Published online March 18, 2021. doi:10.1001/jamaoto.2021.0086
Key Points

Question  What is the baseline functional connectivity in adults with postviral olfactory dysfunction (PVOD), and what changes in functional connectivity are observed after 3 months of olfactory training (OT)?

Findings  In this prospective cohort study of 16 adults with PVOD and 20 control participants, an increased connectivity within the visual cortex was observed at baseline in those with PVOD. After 3 months of OT, this connectivity in the visual cortex decreased and was replaced with an increased connection between regions of the brain involved in olfaction.

Meaning  These findings suggest a bimodal interaction between the visual and olfactory cortex during OT and that further understanding of the association between these 2 senses for adults with PVOD may be useful to enhance existing OT programs.


Importance  Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent.

Objective  To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging.

Design, Setting, and Participants  This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin’ Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020.

Interventions  Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention.

Main Outcome and Measures  The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin’ Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures.

Results  A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum.

Conclusions and Relevance  The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.

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