Impact of experimental inflammation on the neuronal processing of cardiac interoceptive signals and heart rate variability in humans

Interoception, or the perception of internal somatic states, is crucial for signaling the individual to take care of the body when needed. It enables behavioral adaptations to sickness states, which further impact autonomic nervous system (ANS) activity. Whether acute inflammation affects interoceptive processing and how this relates to sickness behavior remains unknown. Therefore, we investigated interoceptive processing in participants undergoing experimental endotoxemia. In neuroimaging research, heartbeat-evoked potentials (HEP) - defined as event-related potentials time-locked to electrocardiogram (ECG) R-waves during electroencephalogram (EEG) recordings - have emerged as a promising metric for cardiac interoceptive processing. We analyzed the effects of intravenous administration of lipopolysaccharide (LPS; 0.4 ng/kg) or placebo, on HEP amplitudes and ANS functioning in healthy, female participants (n = 52) during 8 min resting-state EEG and ECG recordings before and 2 h after injections. Our results showed increased cortisol and cytokine levels in the LPS group, along with increased sympathetic and decreased parasympathetic activity 2 h after injections compared to the placebo group. Placebo-injected participants exhibited lower post injection-baseline differences in HEP amplitudes in an early timeframe (255-455 ms), indicating lower HEPs 2 h after administrations. Moreover, post-injection HEP amplitudes differed between groups, suggesting that while participants in the placebo group showed altered HEP amplitudes after injection, HEPs remained unresponsive to LPS administration. These findings are discussed in the context of predictive processing, expectation violation and attention direction to external and interoceptive cues. Future research should further investigate the role of LPS dose and explore behavioral measures of interoception under experimental inflammation.