Olfactory Categorization Is Shaped by a Transmodal Cortical Network for Evaluating Perceptual Predictions.

Creating and evaluating predictions are considered important features in sensory perception. Little is known about processing differences between the senses and their cortical substrates. Here, we tested the hypothesis that olfaction, the sense of smell, would be highly dependent on (nonolfactory) object-predictive cues and involve distinct cortical processing features. We developed a novel paradigm to compare prediction error processing across senses. Participants listened to spoken word cues (e.g., "lilac") and determined whether target stimuli (odors or pictures) matched the word cue or not. In two behavioral experiments (total n = 113; 72 female), the disparity between congruent and incongruent response times was exaggerated for olfactory relative to visual targets, indicating a greater dependency on predictive verbal cues to process olfactory targets. A preregistered fMRI study (n = 30; 19 female) revealed the anterior cingulate cortex (a region central for error detection) being more activated by incongruent olfactory targets, indicating a role for olfactory predictive error processing. Additionally, both the primary olfactory and visual cortices were significantly activated for incongruent olfactory targets, suggesting olfactory prediction errors are dependent on cross-sensory processing resources, whereas visual prediction errors are not. We propose that olfaction is characterized by a strong dependency on predictive (nonolfactory) cues and that odors are evaluated in the context of such predictions by a designated transmodal cortical network. Our results indicate differences in how predictive cues are used by different senses in rapid decision-making.

A parosmia severity index based on word-classification predicts olfactory abilities and impairment.

Parosmia is an olfactory disorder that involves distortions of specific odors that may co-occur with anosmia, loss of smell of other odors. Little is known about which odors frequently trigger parosmia, and measures of parosmia severity are lacking. Here, we present an approach to understand and diagnose parosmia that is based on semantic properties (e.g., valence) of words describing odor sources ("fish", "coffee", etc.). Using a data-driven method based on natural language data, we identified 38 odor descriptors. Descriptors were evenly dispersed across an olfactory-semantic space, which was based on key odor dimensions. Parosmia patients (n = 48) classified the corresponding odors in terms of whether they trigger parosmic or anosmic sensations. We investigated whether these classifications are related to semantic properties of the descriptors. Parosmic sensations were most often reported for words describing unpleasant odors of inedibles that are highly associated to olfaction (e.g., "excrement"). Based on PCA modeling, we derived the Parosmia Severity Index-a measure of parosmia severity that can be determined solely from our non-olfactory behavioral task. This index predicts olfactory-perceptual abilities, self-reported olfactory impairment, and depression. We thus provide a novel approach for investigating parosmia and establishing its severity that does not require odor exposure. Our work may enhance our understanding of how parosmia changes over time and how it is expressed differently across individuals.

Perceptual odor qualities predict successful odor identification in old age.

Odor identification is a common assessment of olfaction, and it is affected in a large number of diseases. Identification abilities decline with age, but little is known about whether there are perceptual odor features that can be used to predict identification. Here, we analyzed data from a large, population-based sample of 2,479 adults, aged 60 years or above, from the Swedish National study on Aging and Care in Kungsholmen. Participants performed both free and cued odor identification tests. In a separate experiment, we assessed perceived pleasantness, familiarity, intensity, and edibility of all odors in the first sample, and examined how odor identification performance is associated with these variables. The analysis showed that high-intensity odors are easier to identify than low-intensity odors overall, but also that they are more susceptible to the negative repercussions of old age. This result indicates that sensory decline is a major aspect of age-dependent odor identification impairment, and suggests a framework where identification likelihood is proportional to the perceived intensity of the odor. Additional analyses further showed that high-performing individuals can discriminate target odors from distractors along the pleasantness and edibility dimensions and that unpleasant and inedible odors show smaller age-related differences in identification. Altogether, these results may guide further development and optimization of brief and efficient odor identification tests as well as influence the design of odorous products targeted toward older consumers.

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.

Olfactory Influences on Visual Categorization: Behavioral and ERP Evidence.

Visual stimuli often dominate nonvisual stimuli during multisensory perception. Evidence suggests higher cognitive processes prioritize visual over nonvisual stimuli during divided attention. Visual stimuli should thus be disproportionally distracting when processing incongruent cross-sensory stimulus pairs. We tested this assumption by comparing visual processing with olfaction, a "primitive" sensory channel that detects potentially hazardous chemicals by alerting attention. Behavioral and event-related brain potentials (ERPs) were assessed in a bimodal object categorization task with congruent or incongruent odor-picture pairings and a delayed auditory target that indicated whether olfactory or visual cues should be categorized. For congruent pairings, accuracy was higher for visual compared to olfactory decisions. However, for incongruent pairings, reaction times (RTs) were faster for olfactory decisions. Behavioral results suggested that incongruent odors interfered more with visual decisions, thereby providing evidence for an "olfactory dominance" effect. Categorization of incongruent pairings engendered a late "slow wave" ERP effect. Importantly, this effect had a later amplitude peak and longer latency during visual decisions, likely reflecting additional categorization effort for visual stimuli in the presence of incongruent odors. In sum, contrary to what might be inferred from theories of "visual dominance," incongruent odors may in fact uniquely attract mental processing resources during perceptual incongruence.

Smell-Based Memory Training: Evidence of Olfactory Learning and Transfer to the Visual Domain.

Human and non-human animal research converge to suggest that the sense of smell, olfaction, has a high level of plasticity and is intimately associated with visual-spatial orientation and memory encoding networks. We investigated whether olfactory memory (OM) training would lead to transfer to an untrained visual memory (VM) task, as well as untrained olfactory tasks. We devised a memory intervention to compare transfer effects generated by olfactory and non-olfactory (visual) memory training. Adult participants were randomly assigned to daily memory training for about 40 days with either olfactory or visual tasks that had a similar difficulty level. Results showed that while visual training did not produce transfer to the OM task, olfactory training produced transfer to the untrained VM task. Olfactory training also improved participants' performance on odor discrimination and naming tasks, such that they reached the same performance level as a high-performing group of wine professionals. Our results indicate that the olfactory system is highly responsive to training, and we speculate that the sense of smell may facilitate transfer of learning to other sensory domains. Further research is however needed in order to replicate and extend our findings.

Interaction Between Odor Identification Deficit and APOE4 Predicts 6-Year Cognitive Decline in Elderly Individuals.

Olfactory identification impairment might indicate future cognitive decline in elderly individuals. An unresolved question is to what extent this effect is dependent on the ApoE-ε4, a genotype associated with risk of Alzheimer's Disease (AD). Given the current concern about reproducibility in empirical research, we assessed this issue in a large sample (n = 1637) of older adults (60 - 96 years) from the population-based longitudinal Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). A hierarchical regression analysis was carried out to determine if a low score on an odor identification test, and the presence of ApoE-ε4, would predict the magnitude of a prospective 6-year change in the Mini-Mental State Examination (MMSE) after controlling for demographic, health-related, and cognitive variables. We found that overall, lower odor identification performance was predictive of cognitive decline, and, as hypothesized, we found that the effect was most pronounced among ApoE-ε4 carriers. Our results from this high-powered sample suggest that in elderly carriers of the ApoE-ε4 allele, odor identification impairment provides an indication of future cognitive decline, which has relevance for the prognosis of AD.

Achieving Olfactory Expertise: Training for Transfer in Odor Identification.

Human olfactory function requires the identification of everyday odors. A characteristic feature of olfaction is that most people find it hard to identify and name common odors, and when odors are presented simultaneously in mixtures, performance is even further compromised. Few studies have systematically assessed how training might enhance identification of single odors and mixtures. This study compared how odor identification training with either single odors or binary mixtures affected identification performance, as well as transfer effects to untrained tasks and odors. Twenty-seven healthy participants (22 F; 28.0 ± 4.7 years old) completed identification training of 8 odors using a list of 16 veridical names. The study included 8 training sessions, as well as pretest and posttest evaluations. Results suggest notable effects of learning, as well as transfer to novel tasks and odors. Overall, training with single odors led to slightly better results than the binary mixture condition, suggesting that in novices, odor identification may be facilitated via consolidation of single odor objects, before learning to dissociate binary mixtures. Overall, odor identification may be trained to generate transfer of learning, although transfer effects were observed in both training methods. Our work suggests that odor identification abilities, while often limited, are highly trainable.

Subjective Olfactory Loss in Older Adults Concurs with Long-Term Odor Identification Decline.

Olfactory impairments may provide early indications of future health outcomes in older adults. Thus, an important question concerns whether these impairments can be self-assessed. Previous findings of cross-sectional studies indicate low correlations between self-reported olfactory function and objective olfactory performance. On the other hand, subjective olfactory impairments predict future dementia and mortality in longitudinal settings. No previous study has assessed the relationship between subjectively and objectively measured decline in olfaction over time. Based on data for 903 older adults derived from the Betula Study, a Swedish population-based prospective study, we tested whether rate-of-change in odor identification could be predicted from subjective olfactory decline over a time span of 10 years during which subjective and objective odor functions were assessed on 2 or 3 test occasions. Indeed, we found that participants who experienced subjective olfactory decline over the study period also had significantly steeper rates of decline in odor identification, even after adjusting for demographic, cognitive, and genetic factors that previously have been associated with performance in odor identification. This association was, however, not present in a subsample with baseline cognitive impairment. We interpret these results as evidence that when asked about whether they have an olfactory impairment or not, older persons are assessing intraindividual olfactory changes, rather than interindividual differences. Our results indicate that subjective olfactory loss reflects objective olfactory decline in cognitively intact older adults. This association might be harnessed to predict health outcomes and highlights the need to develop effective olfactory self-assessments.

Effects of Task Demands on Olfactory, Auditory, and Visual Event-Related Potentials Suggest Similar Top-Down Modulation Across Senses.

A widely held view is that top-down modulation of sensory information relies on an amodal control network that acts through the thalamus to regulate incoming signals. Olfaction lacks a direct thalamic projection, which suggests that it may differ from other modalities in this regard. We investigated the late positive complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants, elicited by intensity-matched olfactory, auditory and visual stimuli, during a condition of focused attention, a neutral condition, and a condition in which stimuli were to be actively ignored. Amplitudes were largest during the attend condition, lowest during the ignore condition, with the neutral condition in between. A Bayesian analysis resulted in strong evidence for similar effects of task across sensory modalities. We conclude that olfaction, despite its unique neural projections, does not differ from audition and vision in terms of task-dependent neural modulation of the LPC.

Body Odor Trait Disgust Sensitivity Predicts Perception of Sweat Biosamples.

Body odors are potent triggers of disgust and regulate social behaviors in many species. The role of olfaction in disgust-associated behaviors has received scant attention in the research literature, in part because olfactory disgust assessments have required laboratory testing with odors. We have devised the "Body Odor Disgust Scale" (BODS) to facilitate research on olfactory disgust. In this study, we evaluated whether individual differences in BODS scores would be associated with the perception of disgust for sweat samples in a laboratory setting. Results show that BODS was a strong predictor of disgust ratings of sweat samples even when controlling for general disgust sensitivity. In contrast, odor intensity ratings were unrelated to BODS scores. Our findings suggest that the BODS scores reflect body odor disgust perception. The BODS scale might facilitate research on olfactory disgust responses and associated behaviors.

Phantom Smells: Prevalence and Correlates in a Population-Based Sample of Older Adults.

Loss of olfactory function is common in old age, but evidence regarding qualitative olfactory dysfunction in the general older population is scarce. The current study investigates the prevalence and correlates of phantom smell experiences (phantosmia) in a population-based study (Swedish National Study on Aging and Care in Kungsholmen [SNAC-K]) of Swedish adults (n = 2569) aged between 60 and 90 years. Phantosmia was assessed through a standardized interview and defined as reporting having experienced an odor percept in the absence of any stimuli in the surrounding environment that could emit the odor. The relationships between phantosmia and demographic, genetic, health-related, and behavioral variables were analyzed with hierarchical logistic regression analyses. The overall prevalence of phantom smells was 4.9%, and was associated with female gender, carrying the met allele of the BDNF gene, higher vascular risk burden, and reporting distorted smell sensations (parosmia). Olfactory dysfunction was, however, not related to phantosmia. The most frequently reported phantom smell was smoky/burnt. A novel finding was that some individuals reported phantom smells with an autobiographical connotation. The results from this study indicate that the prevalence of phantosmia in the general older population is not negligible and that some factors that are beneficial for preserved olfactory function, such as female gender and the BDNF met allele, are also associated with the occurrence of phantom smells.

The Body Odor Disgust Scale (BODS): Development and Validation of a Novel Olfactory Disgust Assessment.

Disgust plays a crucial role in the avoidance of pathogen threats. In many species, body odors provide important information related to health and disease, and body odors are potent elicitors of disgust in humans. With this background, valid assessments of body odor disgust sensitivity are warranted. In the present article, we report the development and psychometric validation of the Body Odor Disgust Scale (BODS), a measure suited to assess individual differences in disgust reaction to a variety of body odors. Collected data from 3 studies (total n = 528) show that the scale can be used either as a unidimensional scale or as a scale that reflects two hypothesized factors: sensitivity to one's own body odors versus those of others. Guided by our results, we reduced the scale to 12 items that capture the essence of these 2 factors. The final version of the BODS shows an excellent internal consistency (Cronbach's αs > 0.9). The BODS subscales show convergent validity with other general disgust scales, as well as with other olfactory functions measures and with aspects of personality that are related to pathogen avoidance. A fourth study confirmed the construct validity of the BODS and its measurement invariance to gender. Moreover, we found that, compared with other general disgust scales, the BODS is more strongly related to perceived vulnerability to disease. The BODS is a brief and valid assessment of trait body odor disgust sensitivity.

Do Valenced Odors and Trait Body Odor Disgust Affect Evaluation of Emotion in Dynamic Faces?

Disgust is a core emotion evolved to detect and avoid the ingestion of poisonous food as well as the contact with pathogens and other harmful agents. Previous research has shown that multisensory presentation of olfactory and visual information may strengthen the processing of disgust-relevant information. However, it is not known whether these findings extend to dynamic facial stimuli that changes from neutral to emotionally expressive, or if individual differences in trait body odor disgust may influence the processing of disgust-related information. In this preregistered study, we tested whether a classification of dynamic facial expressions as happy or disgusted, and an emotional evaluation of these facial expressions, would be affected by individual differences in body odor disgust sensitivity, and by exposure to a sweat-like, negatively valenced odor (valeric acid), as compared with a soap-like, positively valenced odor (lilac essence) or a no-odor control. Using Bayesian hypothesis testing, we found evidence that odors do not affect recognition of emotion in dynamic faces even when body odor disgust sensitivity was used as moderator. However, an exploratory analysis suggested that an unpleasant odor context may cause faster RTs for faces, independent of their emotional expression. Our results further our understanding of the scope and limits of odor effects on facial perception affect and suggest further studies should focus on reproducibility, specifying experimental circumstances where odor effects on facial expressions may be present versus absent.

A designated odor-language integration system in the human brain.

Odors are surprisingly difficult to name, but the mechanism underlying this phenomenon is poorly understood. In experiments using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), we investigated the physiological basis of odor naming with a paradigm where olfactory and visual object cues were followed by target words that either matched or mismatched the cue. We hypothesized that word processing would not only be affected by its semantic congruency with the preceding cue, but would also depend on the cue modality (olfactory or visual). Performance was slower and less precise when linking a word to its corresponding odor than to its picture. The ERP index of semantic incongruity (N400), reflected in the comparison of nonmatching versus matching target words, was more constrained to posterior electrode sites and lasted longer on odor-cue (vs picture-cue) trials. In parallel, fMRI cross-adaptation in the right orbitofrontal cortex (OFC) and the left anterior temporal lobe (ATL) was observed in response to words when preceded by matching olfactory cues, but not by matching visual cues. Time-series plots demonstrated increased fMRI activity in OFC and ATL at the onset of the odor cue itself, followed by response habituation after processing of a matching (vs nonmatching) target word, suggesting that predictive perceptual representations in these regions are already established before delivery and deliberation of the target word. Together, our findings underscore the modality-specific anatomy and physiology of object identification in the human brain.

Effects of testing on subsequent re-encoding and long-term forgetting of action-relevant materials: On the influence of recall type.

Testing one's memory of previously studied information reduces the rate of forgetting, compared to restudy. However, little is known about how this direct testing effect applies to action phrases (e.g., "wash the car") - a learning material relevant to everyday memory. As action phrases consist of two different components, a verb (e.g., "wash") and a noun (e.g., "car"), testing can either be implemented as noun-cued recall of verbs or verb-cued recall of nouns, which may differently affect later memory performance. In the present study, we investigated the effect of testing for these two recall types, using verbally encoded action phrases as learning materials. Results showed that repeated study-test practice, compared to repeated study-restudy practice, decreased the forgetting rate across 1 week to a similar degree for both noun-cued and verb-cued recall types. However, noun-cued recall of verbs initiated more new subsequent learning during the first restudy, compared to verb-cued recall of nouns. The study provides evidence that testing has benefits on both subsequent restudy and long-term retention of action-relevant materials, but that these benefits are differently expressed with testing via noun-cued versus verb-cued recall.

Olfactory impairment and subjective olfactory complaints independently predict conversion to dementia: a longitudinal, population-based study.

We examined whether conversion to dementia can be predicted by self-reported olfactory impairment and/or by an inability to identify odors. Common forms of dementia involve an impaired sense of smell, and poor olfactory performance predicts cognitive decline among the elderly. We followed a sample of 1529 participants, who were within a normal range of overall cognitive function at baseline, over a 10-year period during which 159 were classified as having a dementia disorder. Dementia conversion was predicted from demographic variables, Mini-Mental State Examination score, and olfactory assessments. Self-reported olfactory impairment emerged as an independent predictor of dementia. After adjusting for effects of other predictors, individuals who rated their olfactory sensitivity as "worse than normal" were more likely to convert to dementia than those who reported normal olfactory sensitivity (odds ratio [OR] = 2.17; 95% confidence interval [CI] [1.40, 3.37]). Additionally, low scores on an odor identification test also predicted conversion to dementia (OR per 1 point increase = 0.89; 95% CI [0.81, 0.98]), but these two effects were additive. We suggest that assessing subjective olfactory complaints might supplement other assessments when evaluating the risk of conversion to dementia. Future studies should investigate which combination of olfactory assessments is most useful in predicting dementia conversion.

A cortical pathway to olfactory naming: evidence from primary progressive aphasia.

It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language 'deficit' is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching. In identifying the critical role of the temporal pole and inferior frontal gyrus in transmodal linking and verbalization of olfactory objects, our findings provide a new neurobiological foundation for understanding why even common odours are hard to name.

Italian validation of the body odor disgust scale.

Introduction: Disgust sensitivity to body odors plays a role in a set of psychological mechanisms supposedly evolved to avoid pathogens. To assess individual differences in body odor disgust, we previously developed the body odor disgust scale (BODS) and validated it in English. The BODS presents six scenarios where disgust could be evoked by smells coming from an internal source and an external source. The present study aimed to validate the BODS in the Italian population and to find further evidence for its structural, construct, and criterion validity. Methods: We used two large samples (N = 1,050, F = 527; and N = 402, F = 203, respectively) that were representative of the Italian population for sex and age. Results: Across these two studies, we confirmed the hypothesized bifactor structure, with all the items loading onto a general body odor disgust sensitivity factor, and on two specific factors related to the internal structure. In terms of construct validity, we found that the BODS converged with pathogen disgust sensitivity of the three-domain disgust scale (TDDS) but was distinct from a general propensity to experience negative emotions. The BODS showed criterion validity in predicting the behavioral intentions toward COVID-19 avoidance behavior, although it did not seem to be incrementally valid when compared to the TDDS pathogen subscale. We also established scalar measurement invariance of the BODS regarding gender and found that women display higher levels of BODS. Discussion: Results from the Italian version of the BODS indicate its structural, construct, nomological and criterion validity. Furthermore, our result on sex differences in disgust sensitivity are consistent with previous literature, and we discuss them in the broader context of cross-cultural and primate findings that points toward a possible evolutionary explanation of this difference.