In line with our hypothesis, subjects exposed to an inflammatory challenge, compared to placebo participants, showed a selective increase in amygdala activity to socially threatening images (relative to all other image types). Moreover, among endotoxin-exposed participants, greater amygdala activity in response to socially vs. non-socially threatening images was associated with greater increases in self-reported feelings of social disconnection. Together, these results highlight a possible role for the amygdala in social withdrawal during sickness and are largely consistent with previous animal work on the role of the amygdala in sickness-induced social withdrawal.
These results are also consistent with work linking heightened amygdala activity in response to negative social cues with social withdrawal tendencies. For instance, relative to healthy controls, individuals with social phobia–who tend to fear and avoid certain social situations–display heightened amygdala activity to negative faces (Bruhl et al., 2011
; Evans et al., 2008
; Yoon et al., 2007
; Phan et al., 2006
). Moreover, the extent of amygdala activity to these faces correlates positively with the severity of the social anxiety symptoms (Bruhl et al., 2011
; Phan et al., 2006
). Taken together, these findings highlight the role of amygdala reactivity in social withdrawal tendencies more generally and in inflammatory-induced social withdrawal more specifically.
The results from the current study also shed light on another possible function of social withdrawal behavior. The most commonly described function of social withdrawal is to promote recovery from illness or infection. However, increased amygdala activation in response to inflammation runs counter to a purely rest-facilitating motive, as amygdala activity is often associated with an activated response to fearful, threatening, or high arousal stimuli (Adolphs et al., 1999
; Feinstein et al., 2011
; Hariri et al., 2002
; Whalen et al., 2001
). Thus, inflammatory-induced amygdala activity to negative social cues may be more directly related to a second proposed function of sickness-induced social withdrawal, namely to prevent the spread of infection by minimizing contact with others (Cole, 2006
). Specifically, increased amygdala activity to socially threatening stimuli may lead to avoidance of those stimuli and social withdrawal, thus preventing the spread of infection.
Indeed, according to an epidemiologic simulation of disease transmission within typically structured human social networks, reducing contact with just 10% of one’s social network can increase the survival rate of the larger population by more than half (Cole, 2006
). In addition, these protective effects are amplified when sick individuals selectively withdraw contact from their most socially distant, low-frequency interaction partners, but not from their closer network members (Cole, 2006
). This may occur for two reasons. First, restricting social withdrawal to distant, but not close, interaction partners prevents large jumps of disease through social space. Second, restricting withdrawal to socially distant, rather than close, individuals may increase the likelihood that the sick individual will receive care and help from their close social network members. Thus, there may also be a survival advantage associated with not withdrawing from close others while sick in order to elicit care and help from them. Although the current study did not specifically examine neural responses to images of socially distant vs. close network members, it is possible that threatening faces were interpreted as socially distant whereas smiling faces (the socially non-threatening stimuli) were interpreted as potential sources of care and help, similar to socially close individuals. Additional research that includes neutral facial expressions may help disentangle the effect of withdrawal from socially threatening vs. socially inviting faces, as neutral faces–if interpreted as socially distant–would be expected to elicit amygdala activation, similar to that seen in response to fearful facial expressions. Future work, however, will be needed to more directly examine whether increased amygdala activity to socially threatening vs. socially inviting faces does indeed increase social withdrawal behavior thereby reducing the spread of infection in a social network.
In sum, findings from the current study highlight a neural mechanism by which social withdrawal, a major but understudied feature of sickness behavior, increases following inflammation. In addition, the findings may highlight another possible function of social withdrawal behaviors (Cole, 2006
)–namely to prevent the spread of infection to others thereby increasing the survival chances of social groups; however, more work will need to directly test this hypothesis.