A measure of smell enables the creation of olfactory metamers.

Wavelength is a physical measure of light, and the intricate understanding of its link to perceived colour enables the creation of perceptual entities such as metamers-non-overlapping spectral compositions that generate identical colour percepts1. By contrast, scientists have been unable to develop a physical measure linked to perceived smell, even one that merely reflects the extent of perceptual similarity between odorants2. Here, to generate such a measure, we collected perceptual similarity estimates of 49,788 pairwise odorants from 199 participants who smelled 242 different multicomponent odorants and used these data to refine a predictive model that links odorant structure to odorant perception3. The resulting measure combines 21 physicochemical features of the odorants into a single number-expressed in radians-that accurately predicts the extent of perceptual similarity between multicomponent odorant pairs. To assess the usefulness of this measure, we investigated whether we could use it to create olfactory metamers. To this end, we first identified a cut-off in the measure: pairs of multicomponent odorants that were within 0.05 radians of each other or less were very difficult to discriminate. Using this cut-off, we were able to design olfactory metamers-pairs of non-overlapping molecular compositions that generated identical odour percepts. The accurate predictions of perceptual similarity, and the ensuing creation of olfactory metamers, suggest that we have obtained a valid olfactory measure, one that may enable the digitization of smell.

Olfactory sniffing signals consciousness in unresponsive patients with brain injuries.

After severe brain injury, it can be difficult to determine the state of consciousness of a patient, to determine whether the patient is unresponsive or perhaps minimally conscious1, and to predict whether they will recover. These diagnoses and prognoses are crucial, as they determine therapeutic strategies such as pain management, and can underlie end-of-life decisions2,3. Nevertheless, there is an error rate of up to 40% in determining the state of consciousness in patients with brain injuries4,5. Olfaction relies on brain structures that are involved in the basic mechanisms of arousal6, and we therefore hypothesized that it may serve as a biomarker for consciousness7. Here we use a non-verbal non-task-dependent measure known as the sniff response8-11 to determine consciousness in patients with brain injuries. By measuring odorant-dependent sniffing, we gain a sensitive measure of olfactory function10-15. We measured the sniff response repeatedly over time in patients with severe brain injuries and found that sniff responses significantly discriminated between unresponsive and minimally conscious states at the group level. Notably, at the single-patient level, if an unresponsive patient had a sniff response, this assured future regaining of consciousness. In addition, olfactory sniff responses were associated with long-term survival rates. These results highlight the importance of olfaction in human brain function, and provide an accessible tool that signals consciousness and recovery in patients with brain injuries.

Relationship between odor intensity estimates and COVID-19 prevalence prediction in a Swedish population.

In response to the COVID-19 pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a step-wise manner, monitoring of COVID-19 prevalence is of importance to guide decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r=-0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before wide-spread testing can be facilitated.

SmellSpace: An Odor-Based Social Network as a Platform for Collecting Olfactory Perceptual Data.

A common goal in olfaction research is modeling the link between odorant structure and odor perception. Such modeling efforts require large data sets on olfactory perception, yet only a few of these are publicly and freely available. Given that individual odor perception may be informative on personal makeup and interpersonal relationships, we hypothesized that people would gladly provide olfactory perceptual estimates in the context of an odor-based social network. We developed a web-based infrastructure for such a network we called SmellSpace and distributed 10 000 scratch-and-sniff registration booklets each containing a subset of 12 out of 35 microencapsulated odorants. Within ~100 days, we obtained data from ~1000 participants who rated the odorants along 13 verbal descriptors. To verify that these estimates are comparable to lab-collected estimates we tested 26 participants in a controlled lab setting using the same odorants and descriptors. We observed remarkably high overall group correlations between lab and SmellSpace data, implying that this method provides for credible group-representations of odorants. We further estimated the usability of the data by applying to it two previously published models that used odorant structure alone to predict either odorant pleasantness or pairwise odorant perceptual similarity. We observed statistically significant predictions in both cases, thus further implying that the current data may be helpful toward future efforts of modeling olfactory perception from structure. We conclude that an odor-based social network is a potentially useful instrument for collecting extensive data on olfactory perception and here post the complete raw data set from the first ~1000 participants.

From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures.

Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose.

An olfactory self-test effectively screens for COVID-19.

Background: Key to curtailing the COVID-19 pandemic are wide-scale screening strategies. An ideal screen is one that would not rely on transporting, distributing, and collecting physical specimens. Given the olfactory impairment associated with COVID-19, we developed a perceptual measure of olfaction that relies on smelling household odorants and rating them online. Methods: Each participant was instructed to select 5 household items, and rate their perceived odor pleasantness and intensity using an online visual analogue scale. We used this data to assign an olfactory perceptual fingerprint, a value that reflects the perceived difference between odorants. We tested the performance of this real-time tool in a total of 13,484 participants (462 COVID-19 positive) from 134 countries who provided 178,820 perceptual ratings of 60 different household odorants. Results: We observe that olfactory ratings are indicative of COVID-19 status in a country, significantly correlating with national infection rates over time. More importantly, we observe indicative power at the individual level (79% sensitivity and 87% specificity). Critically, this olfactory screen remains effective in participants with COVID-19 but without symptoms, and in participants with symptoms but without COVID-19. Conclusions: The current odorant-based olfactory screen adds a component to online symptom-checkers, to potentially provide an added first line of defense that can help fight disease progression at the population level. The data derived from this tool may allow better understanding of the link between COVID-19 and olfaction.

Sniffing the human body volatile hexadecanal blocks aggression in men but triggers aggression in women.

In terrestrial mammals, body volatiles can effectively trigger or block conspecific aggression. Here, we tested whether hexadecanal (HEX), a human body volatile implicated as a mammalian-wide social chemosignal, affects human aggression. Using validated behavioral paradigms, we observed a marked dissociation: Sniffing HEX blocked aggression in men but triggered aggression in women. Next, using functional brain imaging, we uncovered a pattern of brain activity mirroring behavior: In both men and women, HEX increased activity in the left angular gyrus, an area implicated in perception of social cues. HEX then modulated functional connectivity between the angular gyrus and a brain network implicated in social appraisal (temporal pole) and aggressive execution (amygdala and orbitofrontal cortex) in a sex-dependent manner consistent with behavior: increasing connectivity in men but decreasing connectivity in women. These findings implicate sex-specific social chemosignaling at the mechanistic heart of human aggressive behavior.

Are humans constantly but subconsciously smelling themselves?

All primates, including humans, engage in self-face-touching at very high frequency. The functional purpose or antecedents of this behaviour remain unclear. In this hybrid review, we put forth the hypothesis that self-face-touching subserves self-smelling. We first review data implying that humans touch their faces at very high frequency. We then detail evidence from the one study that implicated an olfactory origin for this behaviour: This evidence consists of significantly increased nasal inhalation concurrent with self-face-touching, and predictable increases or decreases in self-face-touching as a function of subliminal odourant tainting. Although we speculate that self-smelling through self-face-touching is largely an unconscious act, we note that in addition, humans also consciously smell themselves at high frequency. To verify this added statement, we administered an online self-report questionnaire. Upon being asked, approximately 94% of approximately 400 respondents acknowledged engaging in smelling themselves. Paradoxically, we observe that although this very prevalent behaviour of self-smelling is of concern to individuals, especially to parents of children overtly exhibiting self-smelling, the behaviour has nearly no traction in the medical or psychological literature. We suggest psychological and cultural explanations for this paradox, and end in suggesting that human self-smelling become a formal topic of investigation in the study of human social olfaction. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

Unexplained repeated pregnancy loss is associated with altered perceptual and brain responses to men's body-odor.

Mammalian olfaction and reproduction are tightly linked, a link less explored in humans. Here, we asked whether human unexplained repeated pregnancy loss (uRPL) is associated with altered olfaction, and particularly altered olfactory responses to body-odor. We found that whereas most women with uRPL could identify the body-odor of their spouse, most control women could not. Moreover, women with uRPL rated the perceptual attributes of men's body-odor differently from controls. These pronounced differences were accompanied by an only modest albeit significant advantage in ordinary, non-body-odor-related olfaction in uRPL. Next, using structural and functional brain imaging, we found that in comparison to controls, most women with uRPL had smaller olfactory bulbs, yet increased hypothalamic response in association with men's body-odor. These findings combine to suggest altered olfactory perceptual and brain responses in women experiencing uRPL, particularly in relation to men's body-odor. Whether this link has any causal aspects to it remains to be explored.

Human non-olfactory cognition phase-locked with inhalation.

Olfactory stimulus acquisition is perfectly synchronized with inhalation, which tunes neuronal ensembles for incoming information. Because olfaction is an ancient sensory system that provided a template for brain evolution, we hypothesized that this link persisted, and therefore nasal inhalations may also tune the brain for acquisition of non-olfactory information. To test this, we measured nasal airflow and electroencephalography during various non-olfactory cognitive tasks. We observed that participants spontaneously inhale at non-olfactory cognitive task onset and that such inhalations shift brain functional network architecture. Concentrating on visuospatial perception, we observed that nasal inhalation drove increased task-related brain activity in specific task-related brain regions and resulted in improved performance accuracy in the visuospatial task. Thus, mental processes with no link to olfaction are nevertheless phase-locked with nasal inhalation, consistent with the notion of an olfaction-based template in the evolution of human brain function.

Altered responses to social chemosignals in autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by impaired social communication, often attributed to misreading of emotional cues. Why individuals with ASD misread emotions remains unclear. Given that terrestrial mammals rely on their sense of smell to read conspecific emotions, we hypothesized that misreading of emotional cues in ASD partially reflects altered social chemosignaling. We found no difference between typically developed (TD) and cognitively able adults with ASD at explicit detection and perception of social chemosignals. Nevertheless, TD and ASD participants dissociated in their responses to subliminal presentation of these same compounds: the undetected 'smell of fear' (skydiver sweat) increased physiological arousal and reduced explicit and implicit measures of trust in TD but acted opposite in ASD participants. Moreover, two different undetected synthetic putative social chemosignals increased or decreased arousal in TD but acted opposite in ASD participants. These results implicate social chemosignaling as a sensory substrate of social impairment in ASD.

A social chemosignaling function for human handshaking.

Social chemosignaling is a part of human behavior, but how chemosignals transfer from one individual to another is unknown. In turn, humans greet each other with handshakes, but the functional antecedents of this behavior remain unclear. To ask whether handshakes are used to sample conspecific social chemosignals, we covertly filmed 271 subjects within a structured greeting event either with or without a handshake. We found that humans often sniff their own hands, and selectively increase this behavior after handshake. After handshakes within gender, subjects increased sniffing of their own right shaking hand by more than 100%. In contrast, after handshakes across gender, subjects increased sniffing of their own left non-shaking hand by more than 100%. Tainting participants with unnoticed odors significantly altered the effects, thus verifying their olfactory nature. Thus, handshaking may functionally serve active yet subliminal social chemosignaling, which likely plays a large role in ongoing human behavior.