Human scent guides mosquito thermotaxis and host selection under naturalistic conditions.

The African malaria mosquito Anopheles gambiae exhibits a strong innate drive to seek out humans in its sensory environment, classically entering homes to land on human skin in the hours flanking midnight. To gain insight into the role that olfactory cues emanating from the human body play in generating this epidemiologically important behavior, we developed a large-scale multi-choice preference assay in Zambia with infrared motion vision under semi-field conditions. We determined that An. gambiae prefers to land on arrayed visual targets warmed to human skin temperature during the nighttime when they are baited with carbon dioxide (CO2) emissions reflective of a large human over background air, body odor from one human over CO2, and the scent of one sleeping human over another. Applying integrative whole body volatilomics to multiple humans tested simultaneously in competition in a six-choice assay, we reveal high attractiveness is associated with whole body odor profiles from humans with increased relative abundances of the volatile carboxylic acids butyric acid, isobutryic acid, and isovaleric acid, and the skin microbe-generated methyl ketone acetoin. Conversely, those least preferred had whole body odor that was depleted of carboxylic acids among other compounds and enriched with the monoterpenoid eucalyptol. Across expansive spatial scales, heated targets without CO2 or whole body odor were minimally or not attractive at all to An. gambiae. These results indicate that human scent acts critically to guide thermotaxis and host selection by this prolific malaria vector as it navigates towards humans, yielding intrinsic heterogeneity in human biting risk.

When are puppies receptive to emotion-induced human chemosignals? The cases of fear and happiness.

We report an observational, double-blind, experimental study that examines the effects of human emotional odors on puppies between 3 and 6 months and adult dogs (one year and upwards). Both groups were exposed to control, human fear, and happiness odors in a between subjects' design. The duration of all behaviors directed to the apparatus, the door, the owner, a stranger, and stress behaviors was recorded. A discriminant analysis showed that the fear odor activates consistent behavior patterns for both puppies and adult dogs. However, no behavioral differences between the control and happiness odor conditions were found in the case of puppies. In contrast, adult dogs reveal distinctive patterns for all three odor conditions. We argue that responses to human fear chemosignals systematically influence the behaviors displayed by puppies and adult dogs, which could be genetically prefigured. In contrast, the effects of happiness odors constitute cues that require learning during early socialization processes, which yield consistent patterns only in adulthood.

Sex-specific effects of human chemosignal on perception of angry but not fearful faces.

Androsta-4,16,-dien-3-one (androstadienone), a steroids implicated as a human social chemosignal, has been reported to impact one's emotional perception along the valence axis. The current study takes a step further to examine whether it modulates the perception of angry and fearful faces, two negative emotions that are similar with respect to valence and arousal, but signal different social values. Systematic comparisons of psychophysical data collected from 40 heterosexual men and 45 heterosexual women revealed that androstadienone subconsciously biased heterosexual men toward perceiving the male faces as less angry, while it biased the heterosexual women toward perceiving the female faces as angrier. Meanwhile, androstadienone did not affect the perception of fearful faces in either men or women. These findings indicate that the modulation of androstadienone on negative emotional perceptions is not uniform, suggesting that it alters the perception of specific rather than general negative emotions. In particular, it impacts one's perception of anger, which signals impending aggression, and hence could further impact an individual's social interaction in a sex-specific manner.

Androstadienone modulates human aggression in a sex-dependent manner.

Chemosensory communication is ubiquitous in human social interaction. Androstadienone is a potential candidate human sex pheromone that is associated with social dominance and competition. The aim of the present study was to investigate the effects of androstadienone on aggression. We specifically distinguished two types of aggression, namely proactive and reactive aggression. Two hundred and six male and female participants received either androstadienone or a control carrier in a double-blind, placebo-controlled, between-participants design. Participants performed two aggression tasks, one on reactive aggression and the other on proactive aggression, while they were exposed to the olfactory stimuli. The results revealed that for men, smelling androstadienone reduced both reactive and proactive aggression, whereas it increased reactive aggression in women. These effects were present despite the olfactory stimuli not being explicitly discriminable. These findings provide direct evidence that androstadienone modulates human aggression in a sex-dependent manner.

Male mice and cows perceive human emotional chemosignals: a preliminary study.

Olfactory cues of individuals of the same species or from different species may induce changes in behaviors and physiological reactions in mammals. However, there are few studies on the influence of human odor on animal behavior and welfare, especially those of rodents and farm animals. The present study aimed to investigate whether the odor of a stressed human (in sweat) would modify the behavior of mice and cows. We hypothesized that laboratory and farm animals can perceive human emotions though olfactory cues and that human emotional chemosignals can modify their behavioral reactions and welfare. Two odors of human axillary sweat were collected from engineering students (n = 25, 14 females and 11 males; 21.1 ± 0.7 years old, range: 19-23 years old): a "stress" odor collected after an exam and a "non-stress" odor collected after a standard class. Two experiments were then conducted to test the discrimination of these two odors by male mice (n = 20) under standard conditions and by cows (n = 10) under farm conditions. During the experiments, the behavioral responses of the animals to both odors (through a dispenser for the mice and a bucket for the cows) were observed. The mice produced significantly (p = 0.004) more fecal pellets with the stress odor dispenser than with the non-stress-odor dispenser. The cows spent significantly (p = 0.04) more time smelling the non-stress-odor bucket than control. For both species, the other behaviors observed did not differ significantly between the odors. Mice and cows seemed to perceive and react to stressful human chemosignals. Mice showed physiological reactions that indicated stress in response to the stress odor of humans, while cows showed preference reactions in response to the non-stress odor of humans. This preliminary study showed that laboratory and farm animals, such as male mice and cows, seemed to discriminate certain odors emitted by humans that were likely related to different emotions. Animals may recognize stressful human chemosignals, associate these signals with negative husbandry practices or human-animal relationships, and consequently modify their behavior.

The Function of Fear Chemosignals: Preparing for Danger.

It has been shown that the presence of conspecifics modulates human vigilance strategies as is the case with animal species. Mere presence has been found to reduce vigilance. However, animal research has also shown that chemosignals (e.g., sweat) produced during fear-inducing situations modulate individuals' threat detection strategies. In the case of humans, little is known about how exposure to conspecifics' fear chemosignals modulates vigilance and threat detection effectiveness. This study (N = 59) examined how human fear chemosignals affect vigilance strategies and threat avoidance in its receivers. We relied on a paradigm that simulates a "foraging under threat" situation in the lab, integrated with an eye-tracker to examine the attention allocation. Our results showed that the exposure to fear chemosignals (vs. rest chemosignals and a no-sweat condition) while not changing vigilance behavior leads to faster answers to threatening events. In conclusion, fear chemosignals seem to constitute an important warning signal for human beings, possibly leading their receiver to a readiness state that allows faster reactions to threat-related events.

Sex differences in the behavioral responses of dogs exposed to human chemosignals of fear and happiness.

This research focuses on sex differences in the behavioral patterns of dogs when they are exposed to human chemosignals (sweat) produced in happy and fear contexts. No age, breed or apparatus-directed behavior differences were found. However, when exposed to fear chemosignals, dogs' behavior towards their owners, and their stress signals lasted longer when compared to being exposed to happiness as well as control chemosignals. In the happy odor condition, females, in contrast to males, displayed a significantly higher interest to the stranger compared to their owner. In the fear condition, dogs spent more time with their owner compared to the stranger. Behaviors directed towards the door, indicative of exit interest, had a longer duration in the fear condition than the other two conditions. Female dogs revealed a significantly longer door-directed behavior in the fear condition compared to the control condition. Overall the data shows that the effect of exposure to human emotional chemosignals is not sex dependent for behaviors related to the apparatus, the owner or the stress behaviors; however, in the happiness condition, females showed a stronger tendency to interact with the stranger.

Male brain processing of the body odor of ovulating women compared to that of pregnant women.

Female chemical signals underlie the advertising of sexual receptivity and fertility. Whether the body odor of a pregnant woman also has a signaling function with respect to male behavior is yet to be conclusively established. This study examines how the body odors of ovulating and pregnant women differentially affect the behavior of heterosexual men. Body odor samples were collected from 5 pregnant women and 5 matched controls during ovulation. In a double-blind functional magnetic resonance imaging design, 18 heterosexual men were exposed to female body odors during ovulation (OV) and pregnancy (PRG) while being required to indicate the attractiveness of concurrently presented female portrait images. The participants were also required to indicate whether they assumed a depicted woman was pregnant. While neither OV nor PRG altered the perceived attractiveness of a presented face, the men tended to identify the women as pregnant while exposed to a PRG body odor. On the neural level, OV activated a network of the frontotemporal and limbic regions, while PRG activated the superior medial frontal gyrus. The results suggest that the detection of sexual availability activates the male brain regions associated with face processing and reward/motivation, whereas sensing pregnancy activates a region responsible for empathy and prosocial behavior. Thus, the female body odor during pregnancy likely helps foster circumstances conducive to the future care of offspring while the body odor advertising sexual availability promotes mating behavior. The brains of heterosexual men may be capable of unconsciously discriminating between these two types of olfactory stimuli.

Human Chemosignals and Brain Activity: A Preliminary Meta-analysis of the Processing of Human Body Odors.

Across phyla, chemosignals are a widely used form of social communication and increasing evidence suggests that chemosensory communication is present also in humans. Chemosignals can transfer, via body odors, socially relevant information, such as specific information about identity or emotional states. However, findings on neural correlates of processing of body odors are divergent. The aims of this meta-analysis were to assess the brain areas involved in the perception of body odors (both neutral and emotional) and the specific activation patterns for the perception of neutral body odor (NBO) and emotional body odor (EBO). We conducted an activation likelihood estimation (ALE) meta-analysis on 16 experiments (13 studies) examining brain activity during body odors processing. We found that the contrast EBO versus NBO resulted in significant convergence in the right middle frontal gyrus and the left cerebellum, whereas the pooled meta-analysis combining all the studies of human odors showed significant convergence in the right inferior frontal gyrus. No significant cluster was found for NBOs. However, our findings also highlight methodological heterogeneity across the existing literature. Further neuroimaging studies are needed to clarify and support the existing findings on neural correlates of processing of body odors.

Reproducible research into human chemical communication by cues and pheromones: learning from psychology's renaissance.

Despite the lack of evidence that the 'putative human pheromones' androstadienone and estratetraenol ever were pheromones, almost 60 studies have claimed 'significant' results. These are quite possibly false positives and can be best seen as potential examples of the 'reproducibility crisis', sadly common in the rest of the life and biomedical sciences, which has many instances of whole fields based on false positives. Experiments on the effects of olfactory cues on human behaviour are also at risk of false positives because they look for subtle effects but use small sample sizes. Research on human chemical communication, much of it falling within psychology, would benefit from vigorously adopting the proposals made by psychologists to enable better, more reliable science, with an emphasis on enhancing reproducibility. A key change is the adoption of study pre-registration and/or Registered Reports which will also reduce publication bias. As we are mammals, and chemical communication is important to other mammals, it is likely that chemical cues are important in our behaviour and that humans may have pheromones, but new approaches will be needed to reliably demonstrate them. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

The scent of emotions: A systematic review of human intra- and interspecific chemical communication of emotions.

OBJECTIVE: The sense of olfaction has been considered of minor importance in human communication. In recent years, evidence has emerged that humans might be influenced by unconscious messages sent through chemosignals in body odors. Data concerning the ability of humans to recognize fear, maybe related to the evolutionary role of these emotions in the fight-or-flight reactions, are well known. METHODS: To further understand the role of emotional chemosignals in mediating communication in humans and its influence on animal behaviors, we conducted a systematic literature review. RESULTS: Chemosignals derived from axillary odors collected under a variety of emotional stimuli and sad tears in humans affect receivers' social interactions, danger detection and risk-taking behavior, social aspects of eating, and performance under stressing conditions. In addition, beyond the fight-or-flight response, even the body odors of happiness can be perceived by others. Furthermore, human chemosignals can influence behaviors and stressful responses in animals, particularly dogs and horses, which may partially explain their special relationship with humans. CONCLUSION: Our review highlights the importance of chemosignaling in human intra- and interspecific interactions and suggests the need for further investigations, both in physiological conditions and in patients with psychiatric or neurodegenerative disorders.

Sexual Chemosignals: Evidence that Men Process Olfactory Signals of Women's Sexual Arousal.

Research suggests that humans can communicate emotional states (e.g., fear, sadness) via chemosignals. However, thus far little is known about whether sexual arousal can also be conveyed through chemosignals and how these signals might influence the receiver. In three experiments, and a subsequent mini meta-analysis, support was found for the hypothesis that men can process the scent of sexually aroused women and that exposure to these sexual chemosignals affect the subsequent perceptions and sexual motivation of men. Specifically, Experiment 1 revealed that men evaluate the axillary sweat of sexually aroused women as more attractive, compared to the scent of the same women when not sexually aroused. In addition, Experiment 2 showed that exposure to sexual chemosignals increased the men's sexual arousal. Experiment 3 found support for the thesis that exposure to sexual chemosignals would increase sexual motivation. As predicted, men devoted greater attention to and showed greater interest in mating with women who displayed sexual cues (e.g., scantily dressed, in seductive poses). By contrast, exposure to the sexual chemosignals did not alter males' attention and mating interest toward women who displayed no sexual cues. It is discussed how sexual chemosignals may function as an additional channel in the communication of sexual interest and how contextual factors can influence the dynamics of human sexual communication.

Enhancing attraction of the vector mosquito Aedes albopictus by using a novel synthetic odorant blend.

BACKGROUND: The Asian tiger mosquito, Aedes albopictus, an increasingly relevant arboviral vector, has spread worldwide. However, currently available tools are limited in terms of effective monitoring of vector populations and accurate determination of the extent of viral transmission, especially before and during outbreaks. Therefore, it is essential to develop novel monitoring and surveillance tools, particularly those that target adult mosquitoes and enhance the trapping efficiency for Ae. albopictus. METHODS: A variety of human body odorants associated with different types of mosquito olfactory receptors were selected, and their attractiveness to Ae. albopictus was tested by a four-arm olfactometer. The optimal compatibility and proportion of the odorants, Mix-5, was observed via orthogonal design analyses. The attractiveness of Mix-5 to Ae. albopictus in the laboratory was assessed using Mosq-ovitraps and Electric Mosquito Killers. In the field, the effectiveness of generic BG-Lure, Mix-5 and a control treatment was compared with a baited Biogents Sentinel trap (BGS-trap) using a Latin square design. RESULTS: In the olfactometer experiments, the attractiveness of the selected candidate compounds at varying dilutions was poor when the individual compounds were used alone. The optimal combination, Mix-5, was generated based on orthogonal design analyses. In the laboratory, the average numbers of female Ae. albopictus mosquitoes attracted by the synthetic odorant blend Mix-5 were 27.00 and 27.50, compared with 12.00 and 14.83 for the control, when using Mosq-ovitraps and Electric Mosquito Killers, respectively. In the field, the average number of Ae. albopictus female mosquitoes trapped by Mix-5 was 9.67 females/trap, whereas the average numbers for BG-Lure and the control were 7.78 and 4.47, respectively. The lure also played an important role in attracting Culex quinquefasciatus mosquitoes, and the average numbers of Cx. quinquefasciatus female mosquitoes attracted by Mix-5, BG-Lure and the control were 18.78, 25.11 and 12.22, respectively. CONCLUSIONS: A human odor-based bait blend was developed and exhibited enhanced effectiveness at attracting Ae. albopictus This blend can be used to monitor and trap dengue vector mosquitoes in Chinese cities.

Separating normosmic and anosmic patients based on entropy evaluation of olfactory event-related potentials.

OBJECTIVE: Methods based on electroencephalography (EEG) are used to evaluate brain responses to odors which is challenging due to the relatively low signal-to-noise ratio. This is especially difficult in patients with olfactory loss. In the present study, we aim to establish a method to separate functionally anosmic and normosmic individuals by means of recordings of olfactory event-related potentials (OERP) using an automated tool. Therefore, Shannon entropy was adopted to examine the complexity of the averaged electrophysiological responses. METHODS: A total of 102 participants received 60 rose-like odorous stimuli at an inter-stimulus interval of 10 s. Olfactory-related brain activity was investigated within three time-windows of equal length; pre-, during-, and post-stimulus. RESULTS: Based on entropy analysis, patients were correctly diagnosed for anosmia with a 75% success rate. CONCLUSION: This novel approach can be expected to help clinicians to identify patients with anosmia or patients with early symptoms of neurodegenerative disorders. SIGNIFICANCE: There is no automated diagnostic tool for anosmic and normosmic patients using OERP. However, detectability of OERP in patients with functional anosmia has been reported to be in the range of 50%.

Androstadienone, a putative chemosignal of dominance, increases gaze avoidance among men with high social anxiety.

Socially anxious individuals show increased sensitivity toward social threat signals, including cues of dominance. This sensitivity may account for the hypervigilance and gaze avoidance commonly reported in individuals with social anxiety. This study examines visual scanning behavior in response to androstadienone (androsta-4,16,-dien-3-one), a putative chemosignal of dominance. We tested whether exposure to androstadienone would increase hypervigilance and gaze avoidance among individuals with high social anxiety. In a double-blind, placebo-controlled, within-subject design, 26 participants with high social anxiety and 26 with low social anxiety were exposed to androstadienone and a control solution on two separate days. On each day, an eye-tracker recorded their spontaneous scanning behavior while they viewed facial images of men depicting dominant and neutral poses. The results indicate that among participants with high social anxiety, androstadienone increased gaze avoidance by reducing the percentage of fixations made to the eye-region and the total amount of time spent gazing at the eye-region of the faces. Participants with low social anxiety did not show this effect. These findings indicate that androstadienone serves as a threatening chemosignal of dominance, further supporting the link between hypersensitivity toward social threat cues and the perpetuation of social anxiety.

Women's fertility cues affect cooperative behavior: Evidence for the role of the human putative chemosignal estratetraenol.

Previous studies demonstrating that women's body odor during ovulation is perceived as more attractive suggest that exposure to women's chemosignals of high fertility increases mating motivation. Building on previous evidence showing that cooperative behaviors are perceived as attractive, in the current study we investigated whether chemosignals of women's fertility affect men's tendency to behave cooperatively. In the first experiment we found that in the presence of women's body odor during ovulation, men increase their tendency to apply a cooperative strategy, while their tendency to apply an individualistic strategy decreases. To examine the mechanism underlying this effect, we tested a different sample of men exposed to the putative human pheromone estratetraenol (estra-1,3,5(10),16-tetraen-3-ol) or to a control solution. Exposure toestratetraenol compared with control yielded strikingly similar effects of increased cooperation. The results indicate that women's chemosignals of high fertility increase mating motivation among man, encouraging them to act in a cooperative manner toward others, a response that may highlight their attractive qualities and thus attract mates. We further conclude that estratetraenol may serve as one of the biological agents that mediate the behavioral effects of women's chemosignals of fertility on social behavior.

Human chemosignals modulate emotional perception of biological motion in a sex-specific manner.

Androsta-4,16,-dien-3-one and estra-1,3,5(10),16-tetraen-3-ol have previously been shown to communicate opposite sex information that is differently effective to the two sex groups. The current study critically examines if the two human steroids could facilitate interactions with potential mates rather than competitors by acting on the recipients' emotional perception in a sex-appropriate manner. Using dynamic point-light displays that portray the gaits of walkers whose emotional states are digitally morphed along the valence and the arousal axes, we show that smelling androstadienone subconsciously biases heterosexual women, but not men, towards perceiving the male, but not female, walkers as happier and more relaxed. By contrast, smelling estratetraenol subconsciously biases heterosexual men, but not women, towards perceiving the female, but not male, walkers as happier and more relaxed. These findings indicate that androstadienone and estratetraenol prime the identification of emotionally receptive states for the potential mates with whom they are associated, in manners contingent upon not only the recipients' own sex but also their sex perception of other individuals that ensure sex-appropriate behavior.

Human chemosignals of disgust facilitate food judgment.

Choosing food is not a trivial decision that people need to make daily, which is often subject to social influences. Here, we studied a human homolog of social transmission of food preference (STFP) as observed in rodents and other animals via chemosignals of body secretions. Human social chemosignals (sweat) produced during a disgust or neutral state among a group of donors were presented to participants undergoing a 2-alternative-forced-choice food healthiness judgment task during functional magnetic resonance imaging (fMRI). Response speed and two key signal detection indices-d' (discrimination sensitivity) and ß (response bias)-converged to indicate that social chemosignals of disgust facilitated food healthiness decisions, in contrast to primary disgust elicitors (disgust odors) that impaired the judgment. fMRI analyses (disgust vs. neutral sweat) revealed that the fusiform face area (FFA), amygdala, and orbitofrontal cortex (OFC) were engaged in processing social chemosignals of disgust during food judgment. Importantly, a double contrast of social signaling across modalities (olfactory vs. visual-facial expressions) indicated that the FFA and OFC exhibited preferential response to social chemosignals of disgust. Together, our findings provide initial evidence for human STFP, where social chemosignals are incorporated into food decisions by engaging social and emotional areas of the brain.

Beyond the west: Chemosignaling of emotions transcends ethno-cultural boundaries.

Accumulating evidence has pointed to a human capacity to communicate emotions to others via sweat. So far, these studies have relied exclusively on Western Caucasian samples. Our aim was to test whether the chemosensory communication of emotions extended beyond ethno-cultural boundaries, from Western Caucasians (N = 48) to East Asians (N = 48). To test this, we used well-validated materials and procedures, a double-blind design, a pre-registered analysis plan, and a combination of facial electromyography (EMG) and continuous flash suppression techniques to measure unconscious emotions. Our results show that East Asian (and Western Caucasian) female receivers exposed to the sweat (body odor) of fearful, happy, and neutral Western Caucasian male senders emulate these respective states based on body odors, outside of awareness. More specifically, East Asian (and Western Caucasian) receivers demonstrated significantly different patterns of facial muscle activity when being exposed to fear odor, happy odor, and neutral odor. Furthermore, fear odor decreased the suppression time of all faces on an interocular suppression task (IST), indicating subconscious vigilance, whereas happy odor increased the detection speed of happy faces. These combined findings suggest that the ability to perceive emotional signals from body odor may be a universal phenomenon.