Work

Voxel-wise functional-to-gray matter volume ratios reveal distinct brain patterns in cirrhosis stratified by hepatic encephalopathy history and clinical status

Year: 2026

Type: article

Abstract: Background: Hepatic encephalopathy (HE) is associated with distributed structural and functional brain abnormalities, but how local resting-state functional signals vary relative to gray matter volume (GMV) remains uncertain. Methods: We retrospectively analyzed previously acquired magnetic resonance imaging (MRI) and clinical data from 97 participants after motion exclusion: 38 healthy controls (HCs), 29 patients with cirrhosis who had no history of overt HE and were classified as West Haven grade 0 at enrollment (NHE), and 30 patients in an operationally defined HE group. Voxel-wise regional homogeneity-to-GMV (ReHo-to-GMV) and amplitude of low-frequency fluctuation-to-GMV (ALFF-to-GMV) ratios were assessed in separate 3-group models adjusted for age, sex, education, and mean framewise displacement. Gaussian random-field cluster inference was used for the primary analysis, with 10,000-permutation threshold-free cluster enhancement (TFCE) as a non-parametric sensitivity analysis. Results: Corrected abnormalities were concentrated in HE versus HCs, whereas neither metric showed a corrected HE-versus-NHE difference. ReHo-to-GMV and ALFF-to-GMV each yielded 13 corrected clusters across the test-specific omnibus and directional results. Permutation and local-GMV-adjusted sensitivity analyses supported the principal HE-versus-HC effects. Cross-metric overlap was limited to 31 HCs > HE voxels (Dice = 0.0541), and none of the 48 exploratory region-of-interest clinical associations survived false-discovery-rate correction. Conclusion: These ratios identify partly distinct group-level neuroimaging patterns of local functional signals relative to GMV in cirrhosis, but they should be interpreted as operational imaging measures rather than direct physiological coupling or validated biomarkers.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1969935