Disrupted small world networks in patients without overt hepatic encephalopathy: a resting state fMRI study

To explore changes in functional connectivity and topological organization of brain functional networks in cirrhotic patients with minimal hepatic encephalopathy (MHE) and non hepatic encephalopathy (nonHE) and their relationship with clinical markers.

Resting-state functional MR imaging was acquired in 22 MHE, 29 nonHE patients and 33 healthy controls. Functional connectivity networks were obtained by computing temporal correlations between any pairs of 90 cortical and subcortical regions. Graph analysis measures were quantitatively assessed for each subject. One-way analysis of covariance was applied to identify statistical differences of functional connectivity and network parameters among three groups. Correlations between clinical markers, such as Child-Pugh scores, venous blood ammonia level, and number connection test type A (NCT-A)/digit symbol test (DST) scores, and connectivity/graph metrics were calculated.

Thirty functional connectivities represented by edges were found to be abnormal (P<0.05, FDR corrected) in cirrhotic patients, in which 16 edges (53.3%) were related with sub-cortical regions. MHE patients showed abnormal small-world attributes in the functional connectivity networks. Cirrhotic patients had significantly reduced nodal degree in 8 cortical regions and increased nodal centrality in 3 cortical regions. Twenty edges were correlated with either NCT-A or DST scores, in which 13 edges were related with sub-cortical regions. No correlation was found between Child-Pugh scores and graph theoretical measures in cirrhotic patients.

Disturbances of brain functional connectivity and small world property loss are associated with neurocognitive impairment of cirrhotic patients. Reorganization of brain network occurred during disease progression from nonHE to MHE.