Advancing Olfactory Training: Perspective from patients, neural mechanism, and efficacy

Ph.D. Zetian Li

AutorIn

Ph.D. Zetian Li

Titel

Advancing Olfactory Training: Perspective from patients, neural mechanism, and efficacy

Zitierfähige Url:

https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-1036065

Erstveröffentlichung

2026

Datum der Einreichung

15.04.2025

Datum der Verteidigung

25.03.2026

Abstract (EN)

Introduction The sense of smell plays a vital role in our daily lives, influencing survival, nutrition, social interactions, and emotions. Despite its significance, Olfactory dysfunction (OD) affects approximately 20% of the population, leading to a notable decline in quality of life. Olfactory training (OT) has emerged as an effective approach to improve OD by repeatedly exposing individuals to specific odors. While numerous studies have demonstrated the effectiveness of OT in clinical settings, less is known about OT from the patients' perspectives, particularly the reasons for non-participation. The underlying mechanisms of OT involve both peripheral regeneration of olfactory receptor neurons (ORNs) and central neuroplasticity in the olfactory bulbs (OB) and olfaction-related brain regions. Although standard OT protocols have shown success, adapted training methods may offer even greater benefits. This thesis tries to answer the following questions: (1) What factors influence patients to engage in OT? (2) What are the neural mechanisms underlying OT? (3) How effective is OT in patients and healthy individuals, and can it be improved? Hypotheses Study 1: OT participation is driven by factors such as quality of life impairment, parosmia symptoms, and perceived olfactory improvement. Study 2: OT induces both structural and functional improvements in olfactory-related brain regions. Study 3: OT is effective in improving olfactory function. In healthy individuals, more complex approaches will yield olfactory improvements. Methodology Study 1: A cross-sectional survey was conducted to assess factors influencing OT participation. Four hundred fifty participants completed questionnaires about the demographic information (e.g. age range and sex) and general questions such as the causes and onset of OD based on their opinion. Questions were also included regarding parosmia, phantosmia, OT, and quality of life. Patients were divided into two groups: OT (n = 161), and No OT (n = 289) groups, according to their responses to the question “Are you doing smell training?”. Data analyses were performed using Chi-square analyses, independent t-tests, and logistic regression analysis. Study 2: Twenty female patients with COVID-19 related OD and 19 healthy controls were recruited. They all underwent OT for three months. Before and after OT, Sniffin’ Sticks test was applied for measuring olfactory function; MRI techniques were measured to determine the functional and structural brain changes. N-butanol was selected for functional MRI scanning, delivered birhinally using Teflon™ tubing connected to a portable computer-controlled olfactometer. Stimuli were presented in a block design format, alternating between 8-second “ON” (odor) and 12-second “OFF” (odorless air) blocks. MRI images were processed using SPM12 in MATLAB, with functional data analyzed via a two-level restricted maximum likelihood approach and ROI analyses conducted with the Marsbar toolbox. OB volumes were segmented using ITK-SNAP, and voxel-based morphometry was performed using the CAT12 toolbox. Independent t-test, repeated measures ANCOVA controlling for age, and Pearson correlation analysis were employed in the analyses. Study 3: One hundred participants were divided into four groups (Video: n = 26; Counter: n = 24; OT-only: n = 24, and Control: n = 26). Before and after OT, Sniffin’ Sticks test was applied for measuring olfactory function. Except for control group, three training groups were set up: participants in the Video group followed a guiding video during each session, which included visual and auditory stimuli designed to enhance multisensory integration. Participants in the Counter group received a wearable finger counter to track the number of odors they detected throughout the day, reinforcing odor awareness. In OT only group, participants performed classical OT without additional modifications. Data were analyzed using one-way ANOVA, Chi-square tests, repeated-measures ANOVA and Spearman’s correlation analysis. Results Study 1: Quality of life impairment and perceived olfactory improvement since OD started were the strongest motivators for OT participation. Awareness of OT was low, especially in older adults, and most participants discontinued training within a month. Gender differences in adherence were observed. Study 2: OT improved olfactory function in patients. Importantly, OT increased functional activation in parahippocampus, and increased activation of amygdala and insular in patients. Moreover, the improved olfactory function correlated positively with the enhanced functional activation in these olfactory-related regions. However, structural changes in the OB and other regions were minimal, with only increased GMV in cerebellum. Study 3: OT together with multisensory integration and the attention to daily odors enhanced olfactory function, especially in odor thresholds and discrimination. Conclusions This thesis advances the understanding of OT by integrating patient perspectives, neuroimaging evidence, and training efficacy. Study 1 indicates that patients who experienced a significant decline in quality of life due to OD and those who perceived olfactory improvements since OD started were more likely to engage in OT. However, many patients did not adhere to the training for a sufficient duration. Main barriers for participation included low awareness of OT among older individuals and skepticism about its effectiveness among younger individuals. Given the growing evidence supporting OT’s benefits, clinicians should actively promote OT to patients while emphasizing the importance of long-term adherence for optimal outcomes. Study 2 suggests that OT is linked to improved olfactory function and increased activation in the parahippocampus, insular and amygdala in patients with post-viral OD. The absence of significant structural changes may be due to the relatively short training duration, suggesting that while functional improvements can occur relatively quickly, structural adaptations may require a longer period of training. Study 3 reveals that OT incorporating ancillary approaches, such as multisensory integration and enhanced odor attention, can improve olfactory function in individuals with subjectively normal olfactory function. These modified training methods hold potential for clinical applications.

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