Connectome disruptions after hypoxic-ischaemic injury associate with consciousness disorder severity

Abstract Accurate neuroprognostication of cardiac arrest survivors who are initially comatose after restoration of spontaneous circulation is crucial for guiding patient management. Because hypoxic-ischemic injury is typically diffuse, damage to a network of brain regions is likely involved in the patient’s disorder of consciousness. To quantify these complex brain network changes, graph theoretical methods were applied. We hypothesize that structural connectivity metrics may provide insights into which patients will likely recover consciousness. Eighteen comatose patients (50±22 years, 44% male) and four healthy participants (40±20 years, 50% male) underwent multi-shell high angular diffusion MRI as part of a prospective study. Structural connectivity matrices were constructed using probabilistic tractography to measure the likelihood of connections between anatomical regions. Network topology alterations were quantified using clustering coefficient, global efficiency, and degree. Hub index analysis was performed to explore the impact of anoxic injury on high-degree hubs. Network parameters were compared between patients with arousal recovery (AR, eye-opening to auditory or noxious stimulation) and without arousal recovery (No AR). Analyses were repeated for AR patients who achieved emergence from the minimally conscious state (EMCS) within one-year post-cardiac arrest and AR patients who did not achieve EMCS (AR'). Significant differences were observed between the Controls, AR, and No AR for all four metrics (Kruskal-Wallis Tests, p<0.05). Worsening disorders of consciousness were associated with decreasing brain complexity (Kendall's tau, p<0.01). Post-hoc testing showed Control values were significantly greater than No AR for all metrics (Wilcoxon rank sum, p<0.05). Control values were greater than AR for all metrics (p<0.05), except the clustering coefficient (p=0.36). AR was significantly greater than No AR for all metrics (p<0.05), except for the hub index (p=0.12). Notable differences between AR' and Controls were observed for all metrics (p<0.05), except clustering coefficient (p=0.11). No significant differences were found between AR’ and No AR groups. In contrast, for all metrics, EMCS values were not significantly different compared to the Controls but were significantly different than the No AR cohort values (p<0.05). The hub index analysis revealed disproportionate damage to high-degree nodes such as the thalamus, putamen and precuneus, further linking topological disruption to the severity of outcomes. This study highlights the potential of graph theoretical measures of structural connectivity to guide decisions in the care of comatose cardiac arrest patients. By bridging structural connectivity with clinical outcomes, this research provides valuable insights into the neural mechanisms underlying consciousness and recovery after cardiac arrest.