Multilevel structural covariance network alterations of thalamo-cortical circuit in liver cirrhosis patients without overt hepatic encephalopathy: associations with liver function and imaging transcriptomics

To better understand the alterations of thalamo–cortical circuit in liver cirrhosis without overt hepatic encephalopathy (LC-nOHE) patients, we constructed and analyzed structural covariance network (SCN) and explored the relationship of these alterations with liver function and imaging transcriptomics. Based on T1 weighted structural images of 86 LC-nOHE patients and 62 healthy controls (HCs), we extracted thalamus volume and three cortical morphological features. Then individual thalamo–cortical SCN of three cortical morphological indexes were constructed. Topological properties of SCN and their association with liver function were analyzed. Causal analyses of SCN (CaSCN) were performed to explore the driven effects of thalamus on cortical morphology throughout the liver dysfunction progression. Spatial correlation between CaSCN and normative regional gene-expression profiles were evaluated in LC-nOHE group. Compared to HCs, LC-nOHE patients showed increased thalamus volume and a range of cortical morphological abnormalities. The reduced segregation and decreased integration of thalamo–cortical SCNs were identified at the global level. Nodal centralities of thalamus, supramarginal gyrus and insula were significantly reduced. Degree centrality of thalamus was negatively correlated with liver function. Thalamo–cortical CaSCN analyses demonstrated that thalamus volume had causal effects on alterations of cortical morphology during liver dysfunction progression in LC-nOHE. The pattern of causal path efficient was spatially correlated with the specific gene expression in normative atlas. These findings provide a comprehensive view of thalamo–cortical circuit progressed vulnerability in LC-nOHE, which is potentially driven by thalamus and associates with imaging transcriptomic patterns.