Vigilance-state instability precedes state-specific LFP changes in acute sepsis

Sleep-wake disturbances are common in sepsis. We previously hypothesized in an anaesthetized sepsis model, that acute changes in sleep-state dynamics were linked to altered in attractor state dynamics. Here, we studied the acute effects of high-dose LPS injection (5mg/kg) on brain activity in a non-anaesthetized survival model.LFP was recorded from dorsal hippocampus and overlaying cortex of 13 male Long-Evans rats before and after LPS injection. Sleep-wake states were scored for cortex and hippocampus, and analyzed using a 3-D power-spectrum-based state-space approach. Additionally, aperiodic and oscillatory activity in each state were investigated.After LPS injection, all rats showed rapid-onset severe fragmentation of wake and NREM and increased state-divergence between cortex and hippocampus that lasted at least 6 hours. Wake and NREM states became spectrally similar in both brain regions, showing a reduction in inter-state distance of ~50% in both hippocampal and cortical signals. However, spectral changes leading to this shift in state-space stabilized an hour after injection, whereas sleep-wake changes appeared immediately after injection. Spectral parametrization showed changes in delta, theta, and gamma oscillations and in aperiodic components. State fragmentation and spectral parameters had partially normalized 24h after LPS injection.Our results show that LPS injection leads to fragmentation of sleep-wake architecture within and between brain regions with subsequent major alterations in state-specific LFP signatures. The rapid onset of sleep-wake changes suggests a neural, rather than humoral mechanism, whereas spectral changes within states could in turn be caused by fragmentation, or be mediated by separate humoral and/or glial signaling.