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.

Mammalian pheromones.

Mammalian pheromones control a myriad of innate social behaviors and acutely regulate hormone levels. Responses to pheromones are highly robust, reproducible, and stereotyped and likely involve developmentally predetermined neural circuits. Here, I review several facets of pheromone transduction in mammals, including (a) chemosensory receptors and signaling components of the main olfactory epithelium and vomeronasal organ involved in pheromone detection; (b) pheromone-activated neural circuits subject to sex-specific and state-dependent modulation; and (c) the striking chemical diversity of mammalian pheromones, which range from small, volatile molecules and sulfated steroids to large families of proteins. Finally, I review (d) molecular mechanisms underlying various behavioral and endocrine responses, including modulation of puberty and estrous; control of reproduction, aggression, suckling, and parental behaviors; individual recognition; and distinguishing of own species from predators, competitors, and prey. Deconstruction of pheromone transduction mechanisms provides a critical foundation for understanding how odor response pathways generate instinctive behaviors.

You Smell Dangerous: Communicating Fight Responses Through Human Chemosignals of Aggression.

The ability to detect conspecifics that represent a potential harm for an individual represents a high survival benefit. Humans communicate socially relevant information using all sensory modalities, including the chemosensory systems. In study 1, we investigated whether the body odor of a stranger with the intention to harm serves as a chemosignal of aggression. Sixteen healthy male participants donated their body odor while engaging in a boxing session characterized by aggression-induction methods (chemosignal of aggression) and while performing an ergometer session (exercise chemosignal). Self-reports on aggression-related physical activity, motivation to harm and angry emotions selectively increased after aggression induction. In study 2, we examined whether receivers smelling such chemosignals experience emotional contagion (e.g., anger) or emotional reciprocity (e.g., anxiety). The aggression and exercise chemosignals were therefore presented to 22 healthy normosmic participants in a double-blind, randomized exposure during which affective/cognitive processing was examined (i.e., emotion recognition task, emotional stroop task). Behavioral results indicate that chemosignals of aggression induce an affective/cognitive modulation compatible with an anxiety reaction in the recipients. These findings are discussed in light of mechanisms of emotional reciprocity as a way to convey not only affective but also motivational information via chemosensory signals in humans.

Always follow your nose: the functional significance of social chemosignals in human reproduction and survival.

This article is part of a Special Issue "Chemosignals and Reproduction" Across phyla, chemosensory communication is crucial for mediating a variety of social behaviors, which form the basis for ontogenetic and phylogenetic survival. In the present paper, evidence on chemosensory communication in humans, with special reference to reproduction and survival, will be presented. First, the impact of chemosignals on human reproduction will be reviewed. Work will be presented, showing how chemosensory signals are involved in mate choice and partnership formation by communicating attractiveness and facilitating a partner selection, which is of evolutionary advantage, and furthermore providing information about the level of sexual hormones. In addition to direct effects on phylogenetic survival, chemosignals indirectly aid reproductive success by fostering harm protection. Results will be presented, showing that chemosensory communication aids the emotional bond between mother and child, which in turn motivates parental caretaking and protection, leading to infant survival. Moreover, the likelihood of group survival can be increased through the use of stress-related chemosignals. Stress-related chemosignals induce a stress-related physiology in the perceiver, thereby priming a fight-flight-response, which is necessary for an optimum adaption to environmental harm. Finally, effects of sexual orientation on chemosensory communication will be discussed in terms of their putative role in stabilizing social groups, which might indirectly provide harm protection and foster survival. An integrative model of the presented data will be introduced. In conclusion, an outlook, focusing on the involvement of chemosensory communication in human social behavior and illustrating a novel approach to the significance of chemosensory signals in human survival, will be given.

Chemosignals, hormones and mammalian reproduction.

Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as "pheromones" but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking.

Complementary roles of the main and accessory olfactory systems in mammalian mate recognition.

We review studies conducted in mouse and ferret that have specified roles of both the main and the accessory olfactory nervous systems in the detection and processing of body odorants (e.g., urinary pheromones, extraorbital lacrimal gland secretions, major histocompatibility complex peptide ligands, and anal scent gland secretions) that play an essential role in sex discrimination and attraction between males and females leading to mate choice and successful reproduction. We also review literature that compares the forebrain processing of inputs from the two olfactory systems in the two sexes that underlies heterosexual partner preferences. Finally, we review experiments that raise the possibility that body odorants detected by the main olfactory system contribute to mate recognition in humans.

Chemosignals communicate human emotions.

Can humans communicate emotional states via chemical signals? In the experiment reported here, we addressed this question by examining the function of chemosignals in a framework furnished by embodied social communication theory. Following this theory, we hypothesized that the processes a sender experiences during distinctive emotional states are transmitted to receivers by means of the chemicals that the sender produces, thus establishing a multilevel correspondence between sender and receiver. In a double-blind experiment, we examined facial reactions, sensory-regulation processes, and visual search in response to chemosignals. We demonstrated that fear chemosignals generated a fearful facial expression and sensory acquisition (increased sniff magnitude and eye scanning); in contrast, disgust chemosignals evoked a disgusted facial expression and sensory rejection (decreased sniff magnitude, target-detection sensitivity, and eye scanning). These findings underline the neglected social relevance of chemosignals in regulating communicative correspondence outside of conscious access.

Smelling your way to food: can bed bugs use our odour?

The resurgence in developed countries of the common bed bug, Cimex lectularius, has led to a search for new sustainable methods to monitor and control this human ectoparasite. Because of increased resistance to insecticides, traps baited with attractive cues are considered a promising method to be developed into efficient monitoring tools for bed bugs. Despite their potential as attractants, only a few studies have investigated the odorant cues implicated in the attraction of bed bugs to human hosts. In this study, we used aeration extracts from human volunteers to assess the role of olfaction in host searching by bed bugs. By coupled gas chromatography and single sensillum recordings on all the antennal sensilla, we measured the electrophysiological response elicited by the compounds present in our human odour extracts. Only five compounds were clearly detected by the olfactory receptor neurons housed in the smooth-peg sensilla of the bed bugs. We tested the behavioural effect of these extracts in a still-air arena and showed a gradient of repellence linked to the dose, as well as a higher propensity of local search behaviour associated with human odours containing a lower ratio of 6-methyl-5-hepten-2-one to C(7)-C(10) aldehydes. We conclude that human odour alone has a weak influence on the behaviour of C. lectularius and we propose that human kairomones may have a significant impact on bed bug behaviour in combination with heat and carbon dioxide, the only two currently known attractive vertebrate cues used by bed bugs for host seeking.

Androstadienone in motor reactions of men and women toward angry faces.

The endogenous compound androstadienone modulating the evaluation of others and activating the human fear system was hypothesized in terms of processing socially relevant cues by regulating responses to angry faces. Androstadienone was investigated in association with arm movements of 62 participants (30 women) in response to happy and angry facial expressions. Volunteers pushed away or pulled toward them a joystick as fast as possible on seeing either an angry or a happy cartoon face on a computer screen. This task was repeated twice: once during exposure to androstadienone masked with clove oil and once to clove oil only. In the former condition participants' reaction speed was accelerated, especially when reacting to angry faces. This observation may indicate an androstadienone-related activation of the fear system leading to faster responses to threat signals, assuming an enhanced allocation of attentional resources toward threat-related social cues.

Smelling chemosensory signals of males in anxious versus nonanxious condition increases state anxiety of female subjects.

The hypothesis of this experiment was that humans in an anxious state compared with a nonanxious state are able to increase anxiety levels in other humans via their body odors. Specifically, we hypothesized that male chemosensory anxiety signals compared with neutral chemosignals increase state anxiety of female subjects. Thirteen male subjects participated in 2 different sweat donation sessions: chemosignals were collected during participation in a high rope course (anxiety condition) and in an ergometer workout (neutral condition). State and trait anxiety were evaluated in 20 female odor recipients using Spielberger's state-trait anxiety inventory in a double-blind design. Comparison of state anxiety of odor donors between control and anxiety condition differed significantly indicating that our model of anxiety induction successfully led to the expected change in emotion. Comparison of state anxiety of odor recipients showed a trend toward higher state anxiety in the anxiety condition compared with the neutral condition after 5 min of odor exposure. After 20 min of odor exposure, state anxiety of female subjects was significantly higher during the perception of sweat collected during the anxiety condition in comparison with the perception of sweat collected during the neutral condition. This experiment gives evidence that male anxiety chemosignals compared with neutral chemosignals are capable of inducing an increased state anxiety in female subjects.

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'.

What is a pheromone? Mammalian pheromones reconsidered.

Pheromone communication is a two-component system: signaling pheromones and receiving sensory neurons. Currently, pheromones remain enigmatic bioactive compounds, as only a few have been identified, but classical bioassays have suggested that they are nonvolatile, activate vomeronasal sensory neurons, and regulate innate social behaviors and neuroendocrine release. Recent discoveries of potential pheromones reveal that they may be more structurally and functionally diverse than previously defined.

Pheromone signal transduction in humans: what can be learned from olfactory loss.

Because humans seem to lack neuronal elements in the vomeronasal organ (VNO), many scientists believe that humans are unable to detect pheromones. This view is challenged by the observations that pheromone-like compounds, 4,16-androstadien-3-one (AND) and oestra-1,3,5(10),16-tetraen-3-ol (EST), activate the human hypothalamus. Whether these activations are mediated via VNO, venous blood or olfactory mucosa is presently unknown. To disentangle between the three alternatives, we conducted activation studies in 12 heterosexual males with chronic anosmia because of nasal polyps. Polyposis hampers signal transduction via the olfactory mucosa without interfering with the VNO or the pheromone transport via venous blood. Twelve healthy men served as controls. Subjects were investigated with (15)O-H(2)O PET during smelling of odorless air (base line), AND, EST, vanillin, and acetone. Smelling of EST activated the anterior hypothalamus in controls, but not anosmics. Neither did the anosmics display cerebral activations with AND or vanillin. Clusters were detected only with the trigeminal odorant acetone, and only in the thalamus, brainstem, the anterior cingulate, and parts of the sensorimotor cortex. Direct comparisons with controls (controls-anosmics) showed clusters in the olfactory cortex (amygdala and piriform cortex) with AND, vanillin, and acetone, and in the anterior hypothalamus with EST. The observed absence of olfactory and presence of trigeminal activations in anosmics indicates that polyposis primarily affected signal processing via the olfactory mucosa. The anosmics inability to activate the hypothalamus with EST, therefore, suggests that in healthy men EST signals were primarily transmitted via the olfactory system.

Human axillary odor: are there side-related perceptual differences?

Most studies on perception of human social odors in axillary sweat do not distinguish between samples from the right and left axillae. However, each axilla might not produce identical odor samples due, for instance, to the increased use of one arm as a result of lateralization. The aim of the present study was to test whether odor samples from the right and left axillae provided by right- and left-handed men were perceived differently by female raters. Participants were 38 males and 49 females, aged 19-35 years. Fresh odor samples (cotton pads worn underarm for 24 h) were evaluated for attractiveness, intensity, and masculinity, with left and right samples being presented as independent stimuli. A side-related difference emerged in left-handers only (no difference in right-handers): The odor from the axilla corresponding to the dominant side (left) was rated more masculine and more intense than the other side (right). This effect was limited to the ratings of a restricted group of females, that is, those who did not take hormone-based contraception and were estimated to be in the fertile phase of their menstrual cycle. In conclusion, future studies using axillary odor samples can consider left and right samples as perceptually equivalent stimuli when the participant samples are representative of the general population, which comprises relatively low proportions of left-handed men and spontaneously ovulating fertile women. The results also provide new evidence of the variation of female sensitivity to biologically relevant stimuli across the menstrual cycle.

Human pheromone detection by the vomeronasal organ: unnecessary for mate selection?

Recently, Foltan and Sedy proposed a hypothesis stating that the adult human VNO is integral to the prevention of inappropriate mate selection. In this commentary, we address the authors' assumption that humans have a functional VNO, that pheromones are detected exclusively by the VNO, and that human pheromones are responsible for negative stimuli during mate selection. After examining the published literature on human vomeronasal function, we argue that their hypothesis is critically flawed. We offer a brief review of the adult human VNO in support of our argument.

Functional neuronal processing of body odors differs from that of similar common odors.

Visual and auditory stimuli of high social and ecological importance are processed in the brain by specialized neuronal networks. To date, this has not been demonstrated for olfactory stimuli. By means of positron emission tomography, we sought to elucidate the neuronal substrates behind body odor perception to answer the question of whether the central processing of body odors differs from perceptually similar nonbody odors. Body odors were processed by a network that was distinctly separate from common odors, indicating a separation in the processing of odors based on their source. Smelling a friend's body odor activated regions previously seen for familiar stimuli, whereas smelling a stranger activated amygdala and insular regions akin to what has previously been demonstrated for fearful stimuli. The results provide evidence that social olfactory stimuli of high ecological relevance are processed by specialized neuronal networks similar to what has previously been demonstrated for auditory and visual stimuli.

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.

Smelling a single component of male sweat alters levels of cortisol in women.

Rodents use chemosignals to alter endocrine balance in conspecifics. Although responses to human sweat suggest a similar mechanism in humans, no particular component of human sweat capable of altering endocrine balance in conspecifics has yet been isolated and identified. Here, we measured salivary levels of the hormone cortisol in women after smelling pure androstadienone (4,16-androstadien-3-one), a molecule present in the sweat of men that has been suggested as a chemosignal in humans. We found that merely smelling androstadienone maintained significantly higher levels of the hormone cortisol in women. These results suggest that, like rodents, humans can influence the hormonal balance of conspecifics through chemosignals. Critically, this study identified a single component of sweat, androstadienone, as capable of exerting such influence. This result points to a potential role for synthetic human chemosignals in clinical applications.

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.