High-order brain interactions distinguish wakefulness, anaesthesia, and recovery induced by deep brain stimulation

Understanding how consciousness depends on large-scale brain interactions is key for both the neuroscience of consciousness and clinical translation. However, it requires moving beyond classical pairwise descriptions of functional connectivity, which cannot capture the collective dependencies emerging across multiple brain regions. Here, we use multivariate information theory measures to characterize how higher-order interactions reorganize across states of consciousness. Specifically, we apply O-information to resting-state fMRI data from non-human primates to quantify whether multiregional brain dynamics are dominated by synergistic or redundant information sharing. We analyse two complementary datasets: (i) wakefulness and anaesthesia-induced loss of consciousness using different molecular agents (propofol, sevoflurane, ketamine), and (ii) the recovery of consciousness driven by central thalamic deep brain stimulation during propofol anaesthesia, indexed by behavioural responsiveness. We identify optimal regional subsets whose O-information robustly discriminates conscious from non-responsive states under two complementary optimization polarities. The first captures elevated redundancy in conscious scans that decreases under anaesthesia, providing robust discrimination and placing high-voltage central-thalamus stimulation closer to wakefulness. The second captures a synergy-to-redundancy transition, prominent in multi-anaesthesia conditions but context-dependent across datasets. Discrimination performance depends on interaction order: redundancy-based signatures improve with increasing subset size, whilst synergy-based signatures peak at low orders. Higher-order informational features significantly outperform pairwise functional connectivity, particularly for synergistic signatures which remain invisible to correlations. These findings demonstrate that consciousness is reflected in the reconfiguration of higher-order interaction structures, with distinct informational substrates requiring multivariate characterization beyond pairwise connectivity.