Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback

Abstract

Inflammation, part of the body’s innate immune response, can lead to “sickness behaviors,” as well as alterations in social and affective experiences. Elevated levels of pro-inflammatory cytokines have been associated with increased neural sensitivity to social rejection and social threat, but also decreased neural sensitivity to rewards. However, recent evidence suggests that inflammation may actually enhance sensitivity to certain social rewards, such as those that signal support and care. Despite a growing interest in how inflammation influences neural reactivity to positive and negative social experiences, no known studies have investigated these processes in the same participants, using a similar task. To examine this issue, 107 participants were randomly assigned to receive either placebo or low-dose endotoxin, which safely triggers an inflammatory response. When levels of pro-inflammatory cytokines were at their peak, participants were scanned using fMRI while they received positive, negative, and neutral feedback from an “evaluator” (actually a confederate) about how they came across in an audio-recorded interview. In response to negative feedback (vs. neutral), participants in the endotoxin condition showed heightened neural activity in a number of threat-related neural regions (i.e., bilateral amygdala, dorsal anterior cingulate cortex) and a key mentalizing-related region (i.e., dorsomedial PFC), compared to placebo participants. Interestingly, when receiving positive feedback (vs. neutral), endotoxin led to greater neural activity in the ventral striatum and ventromedial PFC, regions often implicated in processing reward, compared to placebo. Together, these results reveal that individuals exposed to an inflammatory challenge are more “neurally sensitive” to both negative and positive social feedback, suggesting that inflammation may lead to a greater vigilance for both social threats and social rewards.

In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior

“…Results from this study revealed that, in response to negative (vs neutral) feedback, subjects exposed to the inflammatory challenge showed greater activity in the dACC as well as the amygdala, a neural region that responds, in part, to threat (Muscatell et al, 2016). Thus, again, an inflammatory challenge led to increased sensitivity to a negative social experience.…”

“…To date, two broad categories of social experience have been found to be altered as a function of inflammation. Specifically, inflammation alters neural sensitivity to negative social stimuli or experiences (eg, social rejection, receiving negative social feedback, and viewing threatening faces; Eisenberger et al, 2009;Inagaki et al, 2012;Muscatell et al, 2016) as well as sensitivity to positive social stimuli or experiences (eg, viewing close others and receiving positive social feedback; Inagaki et al, 2015;Muscatell et al, 2016). A heightened sensitivity to both positive and negative social stimuli may help an individual to more quickly determine which individuals might be supportive and provide help in times of need and which individuals will not and should be avoided.…”

“…Similarly, another study investigated how inflammation altered reward-related neural activity, this time in response to hearing positive feedback from an evaluator (Muscatell et al, 2016). Although the person providing the feedback was not a close other or social support figure, results showed that subjects exposed to endotoxin (vs placebo) displayed more reward-related activity in the VS as well as in the ventromedial prefrontal cortex, another reward-related neural region, in response to receiving positive feedback (compared with neutral feedback).…”

“…Being in a 'sick state' or a state of heightened inflammation puts a social organism in a particularly vulnerable situation and thus sensitivity to the social world may need to be altered to navigate this more vulnerable situation. Navigating sickness for a social species may be accomplished by: (1) increasing sensitivity to threatening social experiences (Eisenberger et al, 2009;Inagaki et al, 2012;Muscatell et al, 2016) in order to better identify and avoid threats to well-being while in this vulnerable state and (2) increasing approach-related behavior towards close others (Inagaki et al, 2015) or other individuals who might be able to provide support (Muscatell et al, 2016) in order to recruit help and care in order to facilitate recovery from sickness ( Figure 1, left side). Here, we review evidence from both animal and human research showing that states of heightened inflammation lead to several important changes in social behavior.…”

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

“…In addition, typhoid vaccination compared with saline has been shown to affect activity in the substantia nigra, including increased activation during a cognitive Stroop task and decreased activation in response to visual or novel stimuli, which correlated with both psychomotor slowing and increased peripheral blood concentrations of IL-6 (Brydon et al, 2008;Harrison et al, 2015a). Finally, it should be mentioned that neural activation in reward circuitry (ventral striatum and ventromedial PFC (vmPFC)) has also been shown to encode endotoxin-induced increased sensitivity to social rewards, including positive social feedback and increased approach to familiar others (Inagaki et al, 2015;Muscatell et al, 2016).…”