Edited by Noam Sobel, Weizmann Institute, Rehovot, Israel, and accepted by Editorial Board Member Randolph Blake April 26, 2017 (received for review October 26, 2016)
In the perpetual race between evolving organisms and pathogens, the human immune system has evolved to reduce the harm of infections. As part of such a system, avoidance of contagious individuals would increase biological fitness. The present study shows that we can detect both facial and olfactory cues of sickness in others just hours after experimental activation of their immune system. The study further demonstrates that multisensory integration of these olfactory and visual sickness cues is a crucial mechanism for how we detect and socially evaluate sick individuals. Thus, by motivating the avoidance of sick conspecifics, olfactory–visual cues, both in isolation and integrated, may be important parts of circuits handling imminent threats of contagion.
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 face-perception 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.
↵2J.N.L. and M.J.O. contributed equally to this work.
Author contributions: C.R., J.A., J.L., D.K.P., T.S., M.G.P., M.L., J.N.L., and M.J.O. designed research; C.R., D.K.P., M.G.P., J.N.L., and M.J.O. performed research; J.N.L. contributed new reagents/analytic tools; C.R. analyzed data; and C.R., J.A., J.L., T.S., M.L., J.N.L., and M.J.O. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. N.S. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1617357114/-/DCSupplemental.
Edited by Noam Sobel, Weizmann Institute, Rehovot, Israel, and accepted by Editorial Board Member Randolph Blake April 26, 2017 (received for review October 26, 2016)
In the perpetual race between evolving organisms and pathogens, the human immune system has evolved to reduce the harm of infections. As part of such a system, avoidance of contagious individuals would increase biological fitness. The present study shows that we can detect both facial and olfactory cues of sickness in others just hours after experimental activation of their immune system. The study further demonstrates that multisensory integration of these olfactory and visual sickness cues is a crucial mechanism for how we detect and socially evaluate sick individuals. Thus, by motivating the avoidance of sick conspecifics, olfactory–visual cues, both in isolation and integrated, may be important parts of circuits handling imminent threats of contagion.
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 face-perception 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.
↵2J.N.L. and M.J.O. contributed equally to this work.
Author contributions: C.R., J.A., J.L., D.K.P., T.S., M.G.P., M.L., J.N.L., and M.J.O. designed research; C.R., D.K.P., M.G.P., J.N.L., and M.J.O. performed research; J.N.L. contributed new reagents/analytic tools; C.R. analyzed data; and C.R., J.A., J.L., T.S., M.L., J.N.L., and M.J.O. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. N.S. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1617357114/-/DCSupplemental.
