Faced with a person with clear signs of potentially contagious disease, the brain triggers an anticipatory front line immune response, similar to that activated during exposure to a real pathogen. Swiss researchers have characterized this phenomenon, its functioning and its origins through the observation of several behavioral, biological and physiological markers. “Our results illustrate the capacity of the brain to predict what is going on and select the suitable answer”comments Professor Andrea Serino, co -author of the study and neuroscientist at the Vaudois CHU (Lausanne).
In order not to confront participants of the study with a real risk of infection, the researchers created different avatars in a virtual reality environment (VR): neutral, threatening without pathogenic stimulus or with signs of an infection. These avatars are getting closer as the participants go and enter their Personal permanent space (PPS). The volunteers were either equipped with a VR helmet and plunged into the environment against the avatars, or vaccinated against flu to compare with an exposure to a real pathogen. The results of the experiments are published in Nature Neuroscience.
In order to grasp all the supporters of this phenomenon, 248 participants were spread over five experiments:
– Assessment of attitude towards avatars, through ratings, a distance scale and an implicit association test
– Behavioral evaluation of the spatial extent of the Personal Space
– Determination of neurophysiological markers of early detection of a virtual infectious threat when it entered the PPS via an electroencephalogram (EEG)
– Measurement of the immune response by analysis of blood samples
– Identification of the brain areas mobilized by imaging with functional magnetic resonance (IRM).
At the behavioral level, increased sensitivity and avoidance of the infectious threat
The first experience has shown that the perception of infectious avatars evoked an implicit avoidance response compared to neutral and threatening avatars. Thus, the cerebral system governing the Personal Space anticipates contact with a person identified as contagious.
The second test explored the reaction speed in the face of tactile stimulation (delivered by mechanical vibrators) according to the avatar encountered and its distance to the observer (D5 to D1, D1 being the closest). This allowed researchers to define the spatial extent of the PPS at the behavioral level. In the cohort with infectious avatars, the permanent space covered a wide range, from D1 to D4 while it is limited to D1 and D2 in the reference session with a neutral stimulus and to D1 in the other two cohorts (neutral and frightening avatars), without changes between the reference value and the second session. Thus, specifically infectious avatars cause an activation of PPS at greater distances, indicating an anticipation of contact even when the person is distant.
Mobilization of the salience network
The researchers then wanted to identify the neurophysiological markers of the early detection of a virtual infection when it entered the Personal Space compared to a neutral stimulus through a high density EEG (128 channels). For the same visactile test, the Global Field Power (GFP, time variation in the standard deviation between electrodes) differs according to the situation to which the participants are exposed. In the infectious cohort, the researchers noted a significant difference from the GFP, between 129 and 150 ms, depending on the proximity of the avatars, at the parietal and premotic areas.
In order to better locate the brain areas associated with these responses, irmf tests have been undertaken in the same cohort. The researchers compared the brain activation induced by the tactile stimulus between neutral and infectious avatars, a long or short distance from the observer. First of all, multisensory treatment is carried out in a bilateral forenso-spaéto-occipital network. Compared to neutral avatars, the contagious provoke specific activations of the left medial prefrontal cortex and the left anterior insula, the areas of the salience network whose role is the detection and sorting of stimuli – whose threats – to mobilize relevant functional networks.
Activation of innate lymphoid cells and migration in the tissues
The study authors finally tried to find out if the virtual infection triggers a real immune response. Immediately after visualization of neutral avatars, a first blood sample was taken to serve as a reference. The second was taken in the three cohorts after meeting with neutral, frightening and contagious avatars. To compare the response to that induced by a real pathogen, a fourth cohort was vaccinated against flu, without participating in VR simulations.
The early innate immune response was evaluated by measuring the frequency and activation in the peripheral blood of innate lymphoid cells (CLI) and Natural Killer (NK). The results highlight an increase in the frequency and activation of CLIs (in all its subsistence: 1, 2 and precursors) similar in the event of real or virtual and stronger infection than for neutral and frightening simulations. In particular, the activation of ILC1 is associated with a drop in their frequency in the blood, testifying to a migration in the tissues, concordant with an antiviral response. However, no change was observed for the NK.
Thus, the cells of innate immunity react not only to the infections detected in the organism but also to the perception of a pathogenic threat. Infectious anticipation can therefore lead to both behavioral avoidance strategies (social distancing) and by the early activation of the innate immune response, even in a virtual context.