Altered Brain Functional Connectivity in Patients with Cirrhosis and Minimal Hepatic Encephalopathy: A Functional MR Imaging Study

Purpose: To investigate patterns of whole-brain functional connectivity in patients with minimal hepatic encephalopathy (HE) by using functional magnetic resonance (MR) imaging. Materials and Methods: This study was approved by the local institutional review board and was HIPAA compliant. All participants provided written informed consent. Neuropsychiatric tests including number connection test type A and digit symbol test were used to define minimal HE. Twenty-three patients with minimal HE and 25 age-and sex-matched healthy volunteers were included in this study. Resting-state functional MR imaging was performed by using a 3-T MR imaging unit. Functional connectivities between 90 pairs of cortical and subcortical regions in patients with minimal HE were compared with those in control participants, and significantly different connectivities were chosen as connectivities of interest (COIs). Correlations between neuropsychiatric tests and correlation coefficients of COIs were calculated. Results: Among the 51 COIs that were significantly different in patients with minimal HE from those in control participants, 44 connectivities were weaker in patients with minimal HE. All 22 COIs related to subcortical regions of interest (bilateral putamen, pallidum, and thalamus) were weaker in patients with minimal HE. Of 29 cortical COIs, 22 connectivities were weaker and seven were stronger in patients with minimal HE. Nearly all COIs with significant differences correlated with digital symbol test scores (P < .05, false discovery rate corrected). No correlation was found among blood ammonia level, Child-Pugh scores, or any COIs in patients with minimal HE (P > .05, false discovery rate corrected). Conclusion: Widespread cortical and subcortical network connectivity changes that correlated with neuropsychologic impairment were found in patients with minimal HE. In particular, impairment in the basal ganglia-thalamocortical circuit could play an important role in mediating neurocognitive dysfunction, especially for psychomotor speed and attention deficits in patients with minimal HE.