Altered brain dynamic in cirrhotic patients without overt hepatic encephalopathy: State and trait features

Neurocognitive impairment, a prevalent complication in cirrhosis, correlates with disruptions in static functional connectivity(FC) of the brain. This study aims to explore altered spatiotemporal properties of blood oxygen-level dependent(BOLD) signals and elucidate their association with neurocognitive changes in cirrhotic patients. Between March 2023 and February 2025, we recruited 77 cirrhotic patients and 66 healthy controls(HCs) accompanied by resting-state functional magnetic resonance imaging(rs-fMRI) acquisition. Neurocognitive function was evaluated by psychometric hepatic encephalopathy score(PHES). The hidden Markov model(HMM) was used to explain variations in rs-fMRI averaged functional activity(AFA) and FC across the whole-brain by using a set of 5 unique recurring states. This study assessed the stability between different groups by comparing the time spent in each state and the mean duration of visits to each state. Mann Whitney U tests, Kruskal Wallis H test, chi-squared test, correlation analysis. After Bonferroni correction, cirrhotic patients with minimal hepatic encephalopathy(MHE) showed significantly higher temporal stability and proportional time spent in state#1 characterized by lower AFA of frontoparietal network(FPN) and subcortical network and higher AFA of visual network (VN), as well as have lower fractional occupancy(FO) and averaged lifetime(ALT) in state#5, which is characterized by weaker within-network FC and lower AFA of limbic network(LN), salience network(SN), somatosensory motor network(SMN), and default mode network(DMN). We observed a significant positive correlation(Bonferroni corrected) between dynamic properties in state#5 and PHES performance. These findings suggest that disrupted brain functional synchrony across time is present in MHE and is linked to cognitive impairment. • Using a Hidden Markov model, the study identified five distinct spatial states. • Cirrhotic patients with MHE exhibited altered brain functional dynamics in state#1 and state#5, where properties in state#5 were positively correlated with psychometric hepatic encephalopathy score. • Advanced cirrhosis significantly correlated with decreased dynamic measures in state#5.