Processing of Body Odor Signals by the Human Brain

Social behavior is ubiquitous in the animal kingdom and essential for the survival of diverse mammalian species. Social behavior includes attraction of potential mates, the regulation of social distance, the soothing and restoring of social equilibrium, and the engendering of help from conspecifics. All of these social actions seem to be associated with the experience of basic emotions (Levenson 2003) in humans and other mammals (Burgdorf and Panksepp 2006; Panksepp 2011). Whereas the successful operation of such social actions obviously supports phylogenetic survival, it has recently been stated that social complexity was the main promotor of the primate's brain size (Dunbar 1998). A growing number of different studies coherently report that the neocortex in anthropoid primates increases with different indicators of social complexity, e.g., group size, grooming clique size, the frequency of coalitions, and the prevalence of social play (see Dunbar and Shultz 2007a). While predation risk has been postulated as the ultimate cause for group living (Dunbar and Shultz 2007b), social enrichment requires the development of behavioral flexibility, which in turn is essential for the formation of stable social bonds. Within the neocortex, the volume of the ventromedial prefrontal area has been considered to be intimately linked to social competencies in humans (Lewis et al. 2011). In addition, besides coding the biological significance of stimuli in general (Pessoa and Adolphs 2010), the amygdala seems to be the main paleocortical relay for the processing of social information in primates (Emery and Amaral 2000; Sallet et al. 2011) and humans (Bickart et al. 2011).

Social communication is based upon a successful release and processing of different sensory signals, including speech, touch, biological motion, facial expressions, and chemosensory signals. In comparison to the communication via other sensory modalities, social communication through chemosensory signals has several advantages (Wyatt 2003). Chemosensory signals can be used in darkness and can easily cross barriers. Depending on the volatility of the molecules, chemosensory signals might be transmitted across very long distances. In contrast, low volatile molecules might still keep the information for conspecifics at the place of release, while the sender has already disappeared (Pause et al. 1997). Hereby, solely the communication through chemical signals is proficient to carry information about social events that happened in the past. Furthermore, social chemical signals are usually based on a specific mixture of molecules, while the meaning of the signal not only depends on the molecules within the mixture but also on the concentration of each molecule. Therefore, the number of signals which could carry social information is extremely high.

The processing of and reaction to environmental chemical signals might have been of special importance for the evolution of the vertebrate brain. Even as early as 1904, it was proposed that the telencephalon was originally an olfactory structure invaded by other sensory systems over the course of vertebrate evolution (Edinger 1904). In fact, the brains of the jawless fish, the modern representatives of the most primitive vertebrates, lampreys, and hagfish, are dominated by huge olfactory bulbs (Eisthen 1997; Northcutt 2002). The view that the olfactory system of the jawless fish (lamprey) represents the most ancient version of the vertebrate olfactory system is supported by sequence analyses of the olfactory receptor gene family (Freitag et al. 1999). Furthermore, recent high-resolution X-ray computed tomography of fossil mammalian skulls indicates that the special features of the mammalian brain evolved through the improved ability of mammals to analyze and process the complex olfactory environment (Rowe et al. 2011). During successive evolutionary pulses, first, the olfactory bulb and olfactory (piriform) cortex expanded. About 200 million years ago, a species which resembles the basal-most member of Mammaliaformes (Morganucodon) showed a first major pulse in encephalization, with a brain about 50% larger than that of earlier related mammal-like reptiles. This encephalization was mainly due to the expansion of the olfactory bulbs. A second encephalization pulse was assessed in the closest known fossil relative of living mammals (Hadrocodium) and was again associated with a marked increase in brain size, and especially of the olfactory bulbs and the cerebral hemispheres. Finally, the huge olfactory receptor genome developed, which was accompanied by olfactory epithelial growth. It can be concluded from these findings that the ability to optimally adjust to the chemical environment was far more important for the huge encephalization in mammals than the ability to process visual or auditory stimuli.

In summary, evidence is accumulating that during vertebrate and mammalian evolution, the ability to adjust to the chemical complexity of the social and non-social environment was the main or one of the main forces for brain development. In primates, however, social complexity has been considered to be the main promotor of neocortex development. It could be speculated, that social chemical communication in humans is still highly complex and important for phylogenetic survival and successful development. The role of chemical communication in humans might have been strongly underestimated as chemical communication between humans usually does not reach the level of conscious processing. However, it is commonly agreed, that in order to adjust to the environmental social requirements, social signals commonly require a fast and automatic response and are therefore mostly processed implicitly without the allocation of attentional resources (Frith and Frith 2008; Öhman and Mineka 2001; Tamietto and de Gelder 2010). In the long run, the investigation of human chemosensory communication will show how deeply the chemical senses are involved in human communication. In fact, first reports suggest that even highly sophisticated social emotions, like moral disgust, might have their evolutionary origin in the processing of chemical signals (Chapman et al. 2009; for a controversial view see Herz 2011).

Whereas body odors can derive from different body fluids (urine, vaginal secretions, sperm, tears) the products of the glandular systems in the skin have usually been considered to be valid sources of human body odor (for an exception see Gelstein et al. 2011). Out of the three primary gland systems, the sebaceous glands, the eccrine glands and the apocrine glands, the sweat produced by the apocrine glands has received most attention. The apocrine glands are located primarily round the nipples, genitals and the axillary region. They develop fully in puberty and are unique to humans and great apes. Apocrine sweat glands secrete a variety of odor precursors that are transformed into volatile odoriferous substances by bacterial enzymes on the skin surface. The secretion of the aprocrine gland is adrenergic innervated through sympathetic fibers. Therefore, the secretion is related to autonomic activation which in turn is associated with motivational or emotional experiences.

A signal can be defined as a stimulus which carries a message to a receiver. Within social communication, the signal is produced and released by a sender. Thus, in contrast to a pure stimulus, which may or may not carry relevant information, a social signal always conveys specific information between two individuals. Therefore, in understanding human communication, it is necessary to focus on the transmitted information, which can be isolated easiest by analyzing the effect of the communication in the signal receiver. So far, four areas of human chemosensory communication have been studied in more detail, each demonstrating physiological and/ or behavioral consequences of signal perception in the receiver. They are related to kin recognition, mate selection, menstrual cycle synchronicity, and emotional contagion.

Kin recognition is most important for structuring social relations in many diverse species (see Mehdiabadi et al. 2006). In order to promote inclusive fitness, which can be understood as the successful transmission of one's own and relatives' genes to the next generation, pro-social behavior is favored among family members (Hamilton, 1964). However, unrelated individuals, like out-group members are more easily perceived as aversive (Olsson et al. 2005) and more easily attacked (De Dreu et al. 2010). Given the importance of kin recognition, numerous studies have shown that newborns are able to chemosensorily identify their mothers, that mothers and fathers are able to chemosensorily identify their children, that siblings recognize each other by smell, and that even unrelated individuals are able to match family members by smell (see Porter 1999; Porter and Schaal 2003).

Similar to kin recognition, a successful mate selection, which forms the basis for the production of healthy offspring, is also a necessary prerequisite for phylogenetic survival. The major histocompatibility complex (MHC) is a highly polymorphic gene complex. It encodes glycoproteins that deliver peptides to the cell surface during antigen presentation, thereby creating histocompatibility or self identification for the immune system. It has been shown in several species that the individual MHC-type is associated to an individual body odor profile, which can be used to chemosensorily discriminate between conspecifics. Fertile individuals prefer the body odors of partners with a relatively dissimilar MHC type to their own. This preference, in turn, seems to be one of the major reasons for mate selection in many vertebrates (Boehm and Zufall 2006; Restrepo et al. 2006). It has been proposed that this differential mating helps to maintain the high MHC polymorphism within species. A high MHC polymorphism enables the species members to resist to a broader array of pathogens, which is crucial for survival. In reference to the immunological function of the MHC, in humans, it is called human leukocyte antigen (HLA). Humans seem not only to exert body odor preferences for HLA dissimilar individuals but also to preferentially select partners who possess a relatively different HLA type (Havlicek and Roberts 2009; Jacob et al. 2002). Thus, HLA-associated body odors seem to be used as signals for mate choice.

Another research field in human chemosensory communication is related to the phenomenon of menstrual synchrony. Some 40 years ago, McClintock found that women living or spending time together show a synchronized menstrual cycle (McClintock 1971). About 30 years later, it could be demonstrated that this phenomenon is most probably due to the communication of menstrual cycle related chemosignals (Stern and McClintock 1998). Whereas odorless axillary sweat samples of women in the follicular cycle phase shortened the menstrual cycle of the female recipients, chemical signals derived from sweat samples of women in the ovulatory cycle phase lengthened the menstrual cycle phase of the signal receivers. This study was the first to show that not only the behavior, but also the endocrine status in humans is prone to be influenced by human chemosignals. However, the evolutionary significance of synchronized menstrual cycles in women is still debated (Mc Clintock 2002; Schank 2001).

The most recently discovered area of chemosensory communication in humans is related to the detection of danger and emotional contagion. It is common across the animal kingdom that stressed individuals inform their conspecifics via chemosignals about a potential harm (e.g., a predator attack). Even though the release of the signal is associated with an increased risk for the sender to encounter direct threat, the development of this communication might have been evolutionary successful, because all signal receiving conspecifics benefit from signal perception. In rodents, the release of chemosensory alarm signals is associated with activity of the pituitary-adrenal axis and secretion of adrenocorticotropin (ACTH; Abel 1994). Physiological reactions to these signals within the receiver resemble stress-related adaptations (Fanselow 1985; Kikusui et al. 2001; Moynihan et al., 2000). Therefore, it is postulated that the experience of stress can be chemosensorily transmitted from the sender to the receiver.

Across phyla, the perception of such stress-related chemosignals seems to be associated with avoidance of the odor source and immediate withdrawal behavior (von Frisch 1941; Mackay-Sim and Laing 1981; Müller-Velten 1966; Ressler et al. 1968; Suh et al. 2004; Zalaquett and Thiessen 1991). A reliable indicator of the activation of motor systems related to withdrawal behavior is the startle reflex. The startle reflex can be measured in animals (Davis et al. 1993) and humans (Lang et al. 1990) and is increased during states of negative affect and decreased during states of positive affect. As rats (Inagaki et al. 2008, 2009) and humans (Pause et al. 2009, Prehn et al. 2006) show an augmented startle response in the context of chemical stress signals, it is concluded that motor systems related to signal avoidance are automatically primed through the perception of stress-related chemosignals of conspecifics.

Besides the effects on motor behavior, the perception of stress-related chemosignals significantly alters the perception of visual social signals in humans. In the context of chemosensory stress signals, the perceptual acuity to happy facial expressions is reduced (Pause et al. 2004; Zernecke et al. 2011), and the perceptual acuity to negative facial expressions is increased (fear: Zhou and Chen 2009; anger: Mujica-Parodi et al. 2009). Moreover, when presented in the context of chemosensory stress signals, neutral or ambiguous facial expressions attract additional attentional resources (Rubin et al. 2011).Thus, chemosignals related to stress or other negative emotional states reliably alter visual social perception: the acuity for social signals related to safety is reduced while at the same time the acuity for social signals related to harm is increased.

In summary, several studies impressively demonstrate that human body odors convey important social signals. These signals deliver information about kinship, immunogenetic mating characteristics, the endocrine status, and emotional states reflecting potential transient danger. In fact, social communication might be one of the most important functions of chemosensory perception in humans (Stevenson 2009). It should be added that the behavioral significance of single substances (e.g., androgen steroids) which can be detected in human body fluids is far less obvious. This is not surprising, taking into account that usually mixtures of several compounds, which are active only in a certain concentration range, form the biologically active signal (Wyatt, 2003). Therefore, several authors conclude, that in humans, behaviorally relevant properties of single molecules have as yet not been demonstrated (Doty 2010; Pause, 2004a,b; Wyatt 2009; Wysocki and Preti 2004).

So far, the neuronal processing of body odors has been investigated using the event-related potential (ERP) technique, positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). ERPs are the averaged epochs of the electroencephalogram (EEG) that occur time-locked to the presented stimuli. As long as chemosensory stimuli elicit the ERP, the term chemosensory ERP (CSERP) has been applied. Latency and amplitude of the CSERP components provide information about early, pre-attentive, and late evaluative stimulus processing. The CSERP technique offers a very high temporal resolution, but only a poor spatial resolution. By use of the PET technique, biochemical components of neural transmission can be detected, e.g., the regional glucose uptake. As compared to fMRI, the temporal resolution is much and the spatial resolution slightly lower. The fMRI method provides an indirect measure of neural activity measuring the blood flow. This method has the highest spatial resolution and also a relatively good temporal resolution.

In the investigation of olfaction a number of studies could repeatedly demonstrate the activation of primary (piriform cortex, amygdala, entorhinal cortex) and secondary olfactory brain structures (hippocampus, hypothalamus, thalamus, orbitofrontal cortex, insula) through odors (Sobel et al. 2003). While the primary olfactory cortex is composed out of areas receiving direct input from the olfactory bulb, areas of the secondary olfactory cortex are directly connected to brain areas of the primary olfactory cortex.