Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

Duality of Smell: Route-Dependent Effects on Olfactory Perception and Language.

Olfactory research in humans has largely focused on odors perceived via sniffing, orthonasal olfaction, whereas odors perceived from the mouth, retronasal olfaction, are less well understood. Prior work on retronasally presented odors involves animal models and focus mainly on odor sensitivity, but little is known about retronasal olfactory perception and cognition in humans. In this study, we compared orthonasal and retronasal odor presentation routes to investigate differences in odor descriptions and evaluations. Thirty-six individuals participated in a within-subjects study using twelve odors (varying in pleasantness and edibility) in perceptual and semantic tasks. Orthonasal presentation was associated with a better ability to identify odors, and with more concrete (and source-based) language. Exploratory analyses revealed that whereas orthonasal odors were described with words that had visual associations, retronasal odors were described with words that had interoceptive associations. Interestingly, these route-dependent differences in descriptor usage were not explained by differences in sensitivity and intensity, suggesting instead a cognitive and linguistic processing difference between odors presented orthonasally and retronasally. Our results indicate that olfaction is, in fact, a dual sense, in which the routes change the perception of an odor.

Prevalence and correlates of parosmia and phantosmia among smell disorders.

Among those many individuals who experience a reduced odor sensitivity (hyposmia/anosmia), some individuals also have disorders that lead to odor distortion, such as parosmia (i.e. distorted odor with a known source), or odor phantoms (i.e. odor sensation without an odor source). We surveyed a large population with at least one olfactory disorder (N = 2031) and found that odor distortions were common (46%), with respondents reporting either parosmia (19%), phantosmia (11%), or both (16%). In comparison to respondents with hyposmia or anosmia, respondents with parosmia were more likely to be female, young, and suffering from post-viral olfactory loss (P < 0.001), while respondents with phantosmia were more likely to be middle-aged (P < 0.01) and experiencing symptoms caused by head trauma (P < 0.01). In addition, parosmia, compared to phantosmia or anosmia/hyposmia, was most prevalent 3 months to a year after olfactory symptom onset (P < 0.001), which coincides with the timeline of physiological recovery. Finally, we observed that the frequency and duration of distortions negatively affects the quality of life, with parosmia showing a higher range of severity than phantosmia (P < 0.001). Previous research often grouped these distortions together, but our results show that they have distinct patterns of demographics, medical history, and loss in quality of life.

Discrimination of Complex Odor Mixtures: A Study Using Wine Aroma Models.

There are key unanswered questions when it comes to multicomponent odor discrimination. This study was designed to assess discrimination of odorant mixtures that elicit a singular percept. We collected data to address the following two questions: (1) What odor features do humans notice when attempting to discriminate between subtly different odor mixtures? (2) Are odor mixtures easier to discriminate when an odorant is added, compared with when a component is removed? Using modern aroma chemistry techniques, an odor mixture resembling a generic white wine was constructed. This wine odor mixture was modified using a series of three esters which are commonly found in white wines that vary in chain length and branching. Participants performed a sequence of discrimination tasks for the addition/subtraction of modifiers to the base wine at different concentrations. Only one of the esters (ethyl propanoate) led to a discriminable odor mixture. As concentration of the modifying odorant was increased, discrimination of odor mixtures was first reported because of changes in odor mixture familiarity and then intensity. We found similar sensitivity to changes in odor mixtures regardless whether the modifying compound was added or subtracted, suggesting that perceptual stability of odor mixtures is equally dependent on both imputing missing information (pattern completion) and disregarding extraneous information.

SCENTinel 1.0: Development of a Rapid Test to Screen for Smell Loss.

Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening.

Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

Consequences of gaining olfactory function after lifelong anosmia.

We present a rare case in which a patient has gained her smell after lifelong anosmia. The patient was objectively tested and diagnosed with functional anosmia at age 13 and reported they were experiencing a new sensation of smell at age 22. Our results show an electrophysiological signal for two unimodal odorants. The patient had a retronasal score in the hyposmic range and self-reported the ability to smell non-trigeminal odors, but reported being disturbed by the presence of the new sense and co-occurrence of phantosmia. We discuss our case in routes of neurogenesis and non-forming memory association with odors.

Validation study of a novel approach for assessment of retronasal olfactory function with combination of odor thresholds and identification.

PURPOSE: The present study aimed to establish a test battery for the clinical assessment of retronasal odor thresholds and retronasal odor identification. STUDY DESIGN: Prospective case-control series. METHODS: Sixty participants (36 women, 24 men, mean age 37.6 ± 19.4 years) were enrolled in this study; 36 were healthy controls and 24 were patients with olfactory dysfunction. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test battery. Retronasal olfaction was assessed with oral odorant delivery using special containers for threshold function, and with oral tasteless powders for odor identification. RESULTS: Retronasal and orthonasal olfaction were significantly correlated for threshold scores, identification score, and the sum of threshold and identification score (TI score). Validity analyses showed that the retronasal TI score was able to discriminate between healthy controls and patients with olfactory dysfunction. CONCLUSIONS: Normosmic participants can be distinctly differentiated from patients with olfactory dysfunction using a valid test battery comprised of retronasal threshold and identification tests. Based on the current findings, we advocate a TI score of 16 as a cut-off between patients and controls. Therefore, TI scores of 17 and above would indicate retronasal normosmia.

Corona Viruses and the Chemical Senses: Past, Present, and Future.

A wealth of rapidly evolving reports suggests that olfaction and taste disturbances may be manifestations of the novel COVID-19 pandemic. While otolaryngological societies worldwide have started to consider chemosensory evaluation as a screening tool for COVID-19 infection, the true nature of the relationship between the changes in chemosensory ability and COVID-19 is unclear. Our goal with this review is to provide a brief overview of published and archived literature, as well as the anecdotal reports and social trends related to this topic up to April 29, 2020. We also aim to draw parallels between the clinical/chemosensory symptomology reported in association to past coronavirus pandemics (such as SARS and MERS) and the novel COVID-19. This review also highlights current evidence on persistent chemosensory disturbances after the infection has resolved. Overall, our analysis pinpoints the need for further studies: 1) to better quantify olfaction and taste disturbances associated with SARS-CoV-2 infection, compared to those of other viral and respiratory infections, 2) to understand the relation between smell, taste, and chemesthesis disturbances in COVID-19, and 3) to understand how persistent are these disturbances after the infection has resolved.

Cultural determinants of food attitudes in anosmic patients.

The decrease in food enjoyment is a major factor why patients suffer from depression when having anosmia, or total loss of smell. While we have some knowledge about how food preferences and attitudes change with dysosmia, these findings are limited because other factors such as culture are not factored in. It is likely that the culture in which an anosmic patient identifies with will influence how their smell loss impacts their relationship with food. This study examined the current attitudes within the United States and Germany towards foods, focusing on the comparison between anosmic patients (N = 53) and those with a healthy sense of smell (N = 121). A survey was used to collect free responses for liking on a variety of foods (N = 15) that were also rated for their overall liking. Additionally, individuals rated and ranked their liking for sensory attributes in relation to their enjoyment of food. Free responses were classified into categories and subcategories, the frequency of those responses were then compared across groups. The patient population of each culture gave lower importance to aroma and flavor; however, the U.S.A. patient population showed a larger decrease from their healthy counterparts. Furthermore, anosmic patients from the U.S.A. showed less overall liking towards the food stimuli compared to their healthy counterparts, while no such effect observed among the German population. Reasons to enjoy a food were largely explained by the culture, and patients within a culture took on different compensation strategies which we use to explain their effectiveness.

Sensitivity to viscosity changes and subsequent estimates of satiety across different senses.

While it is widely accepted that texture is a multimodal in nature, little research has been published regarding how we use senses other than touch to assess texture. In beverages, humans use texture (i.e. viscosity) information to estimate calories and expected satiety. This study was designed to compare and contrast the sensitivity of humans to changes in viscosity and their ability to estimate satiety through different sensory modalities. Milk samples of varying viscosities were constructed, and 49 participants were asked to perform a series of 2-alternative forced choice tests and identify which sample was thicker. Sensitivity to viscosity changes across different sensory modalities was determined by having each participant consume the samples, listen to the samples pouring, and observe clear vials of the samples. Using vision, participants were notably less sensitive to changes in viscosity when compared to hearing or oral tactile sensations. Interestingly, oral tactile sensations and hearing were almost identical in their viscosity difference thresholds (0.346 cP and 0.360 cP, respectively). Similar patterns were observed when the participants were asked to estimate how full they expected to be after consuming beverage stimuli varying in viscosity. Expected caloric values and satiation were found to change with thickness level when participants were assessing the stimuli through the auditory or tactile modalities. However, these measures of expected caloric value and satiation did not change as a function of viscosity for visual assessment, suggesting the assessment of caloric density and satiation are linked to specific sensory modalities' ability to detect viscosity. This study highlights the relative importance of vision, auditory, and touch to forming our sensory judgements regarding viscosity and subsequent satiety estimations.

Dietary customs and food availability shape the preferences for basic tastes: A cross-cultural study among Polish, Tsimane' and Hadza societies.

Biological significance of food components suggests that preferences for basic tastes should be similar across cultures. On the other hand, cultural factors play an important role in diet and can consequently influence individual preference for food. To date, very few studies have compared basic tastes preferences among populations of very diverse environmental and cultural conditions, and research rather did not involve traditional populations for whom the biological significance of different food components might be the most pronounced. Hence, our study focused on basic taste preferences in three populations, covering a broad difference in diet due to environmental and cultural conditions, market availability, dietary habits and food acquirement: 1) a modern society (Poles, n = 200), 2) forager-horticulturalists from Amazon/Bolivia (Tsimane', n = 138), and 3) hunter-gatherers from Tanzania (Hadza, n = 85). The preferences for basic tastes were measured with sprays containing supra-threshold levels of sweet, sour, bitter, salty, and umami taste solutions. We observed several interesting differences between participating societies. We found that Tsimane' and Polish participants liked the sweet taste more than other tastes, while Hadza participants liked salty and sour tastes more than the remaining tastes. Further, Polish people found bitter taste particularly aversive, which was not observed in the traditional societies. Interestingly, no cross-cultural differences were observed for relative liking of umami taste - it was rated closely to neutral by members of all participating societies. Additionally, Hadza showed a pattern to like basic tastes that are more common to their current diet than societies with access to different food sources. These findings demonstrate the impact of diet and market availability on preference for basic tastes.

Olfactory Performance Can Be Influenced by the Presentation Order, Background Noise, and Positive Concurrent Feedback.

Sniffin' Sticks have become a popular procedure to measure overall olfactory functionality with 3 subtest: phenyl ethyl alcohol threshold test (T), discrimination (D), and identification (I). However, several procedural components specified by the original paper have not been tested nor has the impact of deviations been measured. The aim of the present work was to measure olfactory performance under modified testing procedures. First, the reverse order of subtests (IDT) was compared with more standard practices (TDI). Next, the possible impact of background noise and positive concurrent feedback were assessed. A total of 120 individuals participated in the study where the 3 conditional experiments, each involving 40 participants, were completed. Testing procedures that reversed the presentation order of subtests (I->D->T) scored a significantly lower overall TDI score than standard testing order with the threshold subtest being the most influenced. Additionally, nonverbal background noise lowered overall olfactory performance while concurrent feedback modulated threshold performance. These results emphasize the importance of testing parameters where olfactory perception and tasks may be modulated by adaptation and attentional distraction, respectively. This study helped furthermore to demonstrate that the investigated 3 deviations from the standard procedure revealed a significant impact on the performance outcome in olfactory assessment using the Sniffin' Sticks.

Demystifying wine expertise through the lens of imagination: Descriptions and imagery vividness across sensory modalities.

For most untrained novices, talking about wine or imagining the smells and flavours of wine is difficult. Wine experts, on the other hand, have been found to have better imagery for wine, and are also more proficient in describing wine. Some scholars have suggested that imagery and language are based on similar underlying processes, but no conclusive evidence has been found regarding mental imagery and language production. In this study, we examined the relationship between imagery and language use in both novices and experts. In an online experiment, wine experts and novices were asked to imagine the colour, smell, taste and mouthfeel of wines in different situations, and were asked to rate the vividness of the imagined experience as well as describe it with words. The results show that experts differ from novices on a number of linguistic measures when describing wine, including the number of words used, the type of words used, the concreteness of those words, and the adjective to noun ratio. Similarly, imagery for wine was more vivid in wine experts compared to novices in the modalities of smell, taste, and mouthfeel, in alignment with previous work. Surprisingly, we found that no single linguistic variable significantly predicted the reported vividness of wine imagery, neither in experts nor in novices. However, the linguistic model predicted imagery vividness better using data from experts compared to novices. Taken together, these findings underscore that imagery and language are different facets of wine cognition.

Functional Connectivity of the Chemosenses: A Review.

Functional connectivity approaches have long been used in cognitive neuroscience to establish pathways of communication between and among brain regions. However, the use of these analyses to better understand how the brain processes chemosensory information remains nascent. In this review, we conduct a literature search of all functional connectivity papers of olfaction, gustation, and chemesthesis, with 103 articles discovered in total. These publications largely use approaches of seed-based functional connectivity and psychophysiological interactions, as well as effective connectivity approaches such as Granger Causality, Dynamic Causal Modeling, and Structural Equation Modeling. Regardless of modality, studies largely focus on elucidating neural correlates of stimulus qualities such as identity, pleasantness, and intensity, with task-based paradigms most frequently implemented. We call for further "model free" or data-driven approaches in predictive modeling to craft brain-behavior relationships that are free from a priori hypotheses and not solely based on potentially irreproducible literature. Moreover, we note a relative dearth of resting-state literature, which could be used to better understand chemosensory networks with less influence from motion artifacts induced via gustatory or olfactory paradigms. Finally, we note a lack of genomics data, which could clarify individual and heritable differences in chemosensory perception.

Emerging Pattern of Post-COVID-19 Parosmia and Its Effect on Food Perception.

Olfactory dysfunction is amongst the many symptoms of Long COVID. Whilst most people that experience smell loss post COVID-19 recover their sense of smell and taste within a few weeks, about 10% of cases experience long-term problems, and their smell recovery journey often begins a few months later when everyday items start to smell distorted. This is known as parosmia. The aim of this study was to identify the key food triggers of parosmic distortions and investigate the relationship between distortion and disgust in order to establish the impact of parosmia on diet and quality of life. In this cross-sectional study (n = 727), respondents experiencing smell distortions completed a questionnaire covering aspects of smell loss, parosmia and the associated change in valence of everyday items. There was a significant correlation between strength and disgust (p < 0.0001), and when the selected items were reported as distorted, they were described as either unpleasant or gag-inducing 84% of the time. This change in valence associated with loss of expected pleasure and the presence of strange tastes and burning sensations must certainly lead to changes in eating behaviours and serious longer-term consequences for mental health and quality of life.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19 related olfactory disorders.

It is estimated that 20-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of four possible odors. Those who completed the test (N = 381) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder (anosmia or hyposmia, N = 135), qualitative olfactory disorder (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

Future Directions for Chemosensory Connectomes: Best Practices and Specific Challenges.

Ecological chemosensory stimuli almost always evoke responses in more than one sensory system. Moreover, any sensory processing takes place along a hierarchy of brain regions. So far, the field of chemosensory neuroimaging is dominated by studies that examine the role of brain regions in isolation. However, to completely understand neural processing of chemosensation, we must also examine interactions between regions. In general, the use of connectivity methods has increased in the neuroimaging field, providing important insights to physical sensory processing, such as vision, audition, and touch. A similar trend has been observed in chemosensory neuroimaging, however, these established techniques have largely not been rigorously applied to imaging studies on the chemical senses, leaving network insights overlooked. In this article, we first highlight some recent work in chemosensory connectomics and we summarize different connectomics techniques. Then, we outline specific challenges for chemosensory connectome neuroimaging studies. Finally, we review best practices from the general connectomics and neuroimaging fields. We recommend future studies to develop or use the following methods we perceive as key to improve chemosensory connectomics: (1) optimized study designs, (2) reporting guidelines, (3) consensus on brain parcellations, (4) consortium research, and (5) data sharing.

Assortative mate preferences for height across short-term and long-term relationship contexts in a cross-cultural sample.

Height preferences reflecting positive assortative mating for height-wherein an individual's own height positively predicts the preferred height of their mate-have been observed in several distinct human populations and are thought to increase reproductive fitness. However, the extent to which assortative preferences for height differ strategically for short-term versus long-term relationship partners, as they do for numerous other indices of mate quality, remains unclear. We explore this possibility in a large representative sample of over 500 men and women aged 15-77 from Canada, Cuba, Norway and the United States. Participants' own heights were measured, and they indicated their height preferences for a long-term and short-term mate using graphic stimuli containing metric indices. Replicating the "male-taller norm," participants on average preferred taller-than-average male mates, and shorter-than-average female mates. Positive assortative preferences for height were observed across sexes and samples, however the strength of these height preferences varied with relationship context for men, and not for women. Taller men preferred relatively shorter women for short-term relationships than for long-term relationships, indicating stronger assortative preferences for height in a long-term context. These results provide preliminary evidence that, in addition to mate preferences for other physical traits related to mate quality such as masculinity in the body, face, and voice, assortative preferences for height do vary as a function of expected relationship length, but this was surprisingly only observed in preferences for female height.

International consensus statement on allergy and rhinology: Olfaction.

BACKGROUND: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). METHODS: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. RESULTS: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. CONCLUSION: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.