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Clinical Trial
. 2017 Jun 13;114(24):6400-6405.
doi: 10.1073/pnas.1617357114. Epub 2017 May 22.

Behavioral and Neural Correlates to Multisensory Detection of Sick Humans

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Free PMC article
Clinical Trial

Behavioral and Neural Correlates to Multisensory Detection of Sick Humans

Christina Regenbogen et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

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.

Keywords: body odor; disease avoidance; endotoxin; lipopolysaccharide; sickness cues.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Bar graphs depict participants’ liking ratings (mean ± SEM) of the presented person as a function of the health status of faces (A) and of odors (B). Shorter bars indicate lower liking. ***P < 0.001, *P = 0.04, P = 0.10. C, control odor.
Fig. 2.
Fig. 2.
Bar graphs depict postscanning ratings of all faces and odors (mean ± SEM). ***P < 0.001, **P < 0.01, *P < 0.05.
Fig. 3.
Fig. 3.
Whole-brain activation to visual sickness (A) and olfactory sickness (B) shown as t-contrasts from a random-effects GLM. All activation maps are depicted in neurological convention. The color bar depicts t-values of local maxima peak activation. MCC, middle cingulate cortex; MDT, mediodorsal thalamus; MFG, middle frontal gyrus; OFC, orbitofrontal cortex; SFG, superior frontal gyrus.
Fig. S1.
Fig. S1.
Time-course plots of the BOLD response during all contrasts of interest. For all clusters of interest (region label and MNI coordinates are depicted), peak activation time-course plots illustrate the BOLD response, averaged across 30 participants, during the presentation of sick faces (red line) and healthy faces (blue line). The averaged time-course plots depict the percent of signal change (y axis) across a duration of 25 s (x axis) after stimulus onset. Error bars represent SEM averaged across all participants. Entorh., entorhinal cortex; IFG, inferior frontal gyrus; IPS, interparietal sulcus; MCC, middle cingulate gyrus; MDT, mediodorsal thalamus; MFG, middle frontal gyrus; MOG, middle occipital gyrus; OFC, orbitofrontal cortex; POG, posterior orbital gyrus; SFG, superior frontal gyrus; SPG, superior parietal gyrus.
Fig. 4.
Fig. 4.
Whole-brain activation to olfactory–visual sickness (A) and superadditive sickness (B); t-contrasts are from a random-effects GLM. IFG, inferior frontal gyrus; IPC, inferior parietal gyrus; IPS, inferior parietal sulcus; MDT, mediodorsal thalamus; MOG, middle occipital gyrus; OFC, orbitofrontal cortex; SFG, superior frontal gyrus; SPG, superior parietal gyrus.
Fig. 5.
Fig. 5.
Whole-brain functional connectivity of IPS and superadditive sickness (t test from a random-effects GLM, T > 4.83, FWE peak-level corrected, P < 0.05). Color bars depict t-values of local maxima peak activation. The asterisk indicates that activation of this cluster also encompassed the inferior temporal gyrus and fusiform gyrus. ACC, anterior cingulate cortex; Hipp/Amy, hippocampus/amygdala; hOc1, primary visual cortex; IPL, inferior parietal lobe; MCC, middle cingulate cortex; STG, superior temporal gyrus.
Fig. S2.
Fig. S2.
Effect of LPS administration on measures of sickness (mean ± SEM) in comparison with saline administration on the donor sample (n = 18) used in this study. [For an overview on all donors (n = 22) and measures taken in the LPS administration protocol, please refer to figure 1 in ref. .] LPS administration (solid lines) induces a significant increase in plasma IL-6 log-transformed concentrations and in overall sickness symptoms (59) in comparison with saline administration (dashed lines), demonstrating the validity of the administration protocol. ***P < 0.001, **P < 0.01, *P < 0.05 LPS vs. saline condition. The hatched area represents the time of body odor sampling; the arrow indicates the time of the face shot taken.
Fig. 6.
Fig. 6.
Description of the study design. (A) Face images and odor stimuli were presented simultaneously within a factorial 2 × 3 (faces × odors) design. (B) Description of one single trial, including fixation cross, stimulus presentation and a liking rating. C, control odor; H, healthy; S, sick.
Fig. S3.
Fig. S3.
Photographs of one female donor 2 h after saline injection (Left) and 2 h after LPS injection (Right).

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