Published online Oct 19, 2025. doi: 10.5498/wjp.v15.i10.108861
Revised: June 4, 2025
Accepted: August 8, 2025
Published online: October 19, 2025
Processing time: 148 Days and 24 Hours
Sepsis is a life-threatening condition defined by organ dysfunction, triggered by a dysregulated host response to infection. there is limited published literature combining cognitive impairment with topological property alterations in brain networks in sepsis survivors. Therefore, we employed graph theory and Granger causality analysis (GCA) methods to analyze resting-state functional magnetic resonance imaging (rs-fMRI) data, aiming to explore the topological alterations in the brain networks of intensive care unit (ICU) sepsis survivors. Using correlation analysis, the interplay between topological property alterations and cognitive impairment was also investigated.
To explore the topological alterations of the brain networks of sepsis survivors and their correlation with cognitive impairment.
Sixteen sepsis survivors and nineteen healthy controls from the community were recruited. Within one month after discharge, neurocognitive tests were administered to assess cognitive performance. Rs-fMRI was acquired and the topological properties of brain networks were measured based on graph theory approaches. GCA was conducted to quantify effective connectivity (EC) between brain regions showing positive topological alterations and other regions in the brain. The correlations between topological properties and cognitive were analyzed.
Sepsis survivors exhibited significant cognitive impairment. At the global level, sepsis survivors showed lower normalized clustering coefficient (γ) and small-worldness (σ) than healthy controls. At the local level, degree centrality (DC) and nodal efficiency (NE) decreased in the right orbital part of inferior frontal gyrus (ORBinf.R), NE decreased in the left temporal pole of superior temporal gyrus (TPOsup.L) whereas DC and NE increased in the right cerebellum Crus 2 (CRBLCrus2.R). Regarding directional connection alterations, EC from left cerebellum 6 (CRBL6.L) to ORBinf.R and EC from TPOsup.L to right cerebellum 1 (CRBLCrus1.R) decreased, whereas EC from right lingual gyrus (LING.R) to TPOsup.L increased. The implementation of correlation analysis revealed a negative correlation between DC in CRBLCrus2.R and both Mini-mental state examination (r = -0.572, P = 0.041) and Montreal cognitive assessment (MoCA) scores (r = -0.629, P = 0.021) at the local level. In the CRBLCrus2.R cohort, a negative correlation was identified between NE and MoCA scores, with a statistically significant result of r = -0.633 and P = 0.020.
Frontal, temporal and cerebellar topological property alterations are possibly associated with cognitive impairment of ICU sepsis survivors and may serve as biomarkers for early diagnosis.
Core Tip: This study innovatively integrates graph theory and Granger causality analysis to uncover distinct topological alterations in frontal, temporal, and cerebellar networks of intensive care unit sepsis survivors. Key findings reveal compensatory hyperconnectivity in the right cerebellum Crus 2, inversely linked to cognitive scores, alongside reduced efficiency in frontal and temporal hubs. Disrupted cerebro-cerebellar directional connectivity further highlights network reorganization post-sepsis. These region-specific network deviations, particularly cerebellar dynamics, offer novel neuroimaging biomarkers for early detection of sepsis-associated cognitive impairment, bridging neuropathological mechanisms with clinical outcomes.