Throughout human evolution, infectious diseases have been a primary cause of death. Detection of subtle cues indicating sickness and avoidance of sick conspecifics would therefore be an adaptive way of coping with an environment fraught with pathogens. This study determines how humans perceive and integrate early cues of sickness in conspecifics sampled just hours after the induction of immune system activation, and the underlying neural mechanisms for this detection. In a double-blind placebo-controlled crossover design, the immune system in 22 sample donors was transiently activated with an endotoxin injection [lipopolysaccharide (LPS)]. Facial photographs and body odor samples were taken from the same donors when "sick" (LPS-injected) and when "healthy" (saline-injected) and subsequently were presented to a separate group of participants (n = 30) who rated their liking of the presented person during fMRI scanning. Faces were less socially desirable when sick, and sick body odors tended to lower liking of the faces. Sickness status presented by odor and facial photograph resulted in increased neural activation of odor-and faceperception networks, respectively. A superadditive effect of olfactory-visual integration of sickness cues was found in the intraparietal sulcus, which was functionally connected to core areas of multisensory integration in the superior temporal sulcus and orbitofrontal cortex. Taken together, the results outline a disease-avoidance model in which neural mechanisms involved in the detection of disease cues and multisensory integration are vital parts.body odor | lipopolysaccharide | endotoxin | sickness cues | disease avoidance

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Chemosignals are used by predators to localize prey and by prey to avoid predators. These cues vary between species, but the odor of blood seems to be an exception and suggests the presence of an evolutionarily conserved chemosensory cue within the blood odor mixture. A blood odor component, E2D, has been shown to trigger approach responses identical to those triggered by the full blood odor in mammalian carnivores and as such, is a key candidate as a food/alarm cue in blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual function of affecting both approach and avoidance behavior in a predator-prey predicted manner. E2D evokes approach responses in two taxonomically distant blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses in the prey species Mouse. We extend this by demonstrating that this chemical cue is preserved in humans as well; E2D induces postural avoidance, increases physiological arousal, and enhances visual perception of affective stimuli. This is the first demonstration of a single chemical cue with the dual function of guiding both approach and avoidance in a predator-prey predicted manner across taxonomically distant species, as well as the first known chemosignal that affects both human and non-human animals alike.

Auditory and visual sensory loss has repeatedly been shown to alter abilities in remaining sensory modalities. It is, however, unclear whether sensory loss also impacts multisensory integration; an ability that is fundamental for the perception of the world around us. We determined effects of olfactory sensory deprivation on multisensory perception by assessing temporal as well as semantic aspects of audio-visual integration in 37 individuals with anosmia (complete olfactory sensory loss) and 37 healthy, matched controls. Participants performed a simultaneity judgement task to determine the temporal binding window, and a multisensory object identification task with individually degraded, dynamic visual, auditory, and audio-visual stimuli. Individuals with anosmia demonstrated an increased ability to detect multisensory temporal asynchronies, represented by a narrowing of the audio-visual temporal binding window. Furthermore, individuals with congenital, but not acquired, anosmia demonstrated indications of greater benefits from bimodal, as compared to unimodal, stimulus presentation when faced with degraded, semantic information. This suggests that the absence of the olfactory sense alters multisensory integration of remaining senses by sharpening the perception of cross-modal temporal violations, independent of sensory loss etiology. In addition, congenital sensory loss may further lead to increased gain from multisensory, compared to unisensory, information. Taken together, multisensory compensatory mechanisms at different levels of perceptual complexity are present in individuals with anosmia.

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