Exploratory Behavioral and Neural Effects of Inflammation-Induced Sickness Behavior

Abstract

Sickness behavior entails behavioral changes such as anxiety or fatigue due to increased circulatory proinflammatory cytokine (IL-6) levels. By crossing the blood-brain barrier, IL-6 induces widespread but poorly understood neurological changes that potentially shift the body's energetic prioritization toward immune recovery. The present study focuses on identifying the mechanisms and behavioral consequences of human sickness behavior on exploration. Sickness behavior was hypothesized to demonstrate a decrease in natural human exploration by dopaminergic mechanisms. We assessed this behavioral phenomenon in participants' exploration of a novel virtual open-field test and a gambling task. Upon receiving the vaccine, participants reported decreased attentional impulsivity on the BIS-11 scale and decrease perceived stress. Participants traversed less and paused more in the virtual-reality open-field test when vaccinated, both of which were mediated by immune reactivity as measured by change in IL-6 levels. These findings support goals of sickness behavior: less curiosity to explore virtual-reality is less cognitively expensive, so energy otherwise invested in pursuing curiosities can focus on immune recovery instead. Further studies on how inflammation changes behavior and neurological regions implicated could improve patient quality of life through better diagnosis and management of inflammation-induced side effects such as depression.