Information-Theoretic Functional Connectivity Characterizes Multiscale Network Reorganization in Postoperative Cognitive Decline

Abstract

Postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) is increasingly conceptualized as a system-level disturbance of large-scale brain coordination rather than focal dysfunction. Here, we propose a multiscale neural engineering framework that combines static and dynamic information-theoretic connectivity with graph-theoretical analysis to characterize postoperative network vulnerability and its association with cognitive outcome. Resting-state fMRI was acquired in 14 male CABG patients at an early postoperative baseline (BL) and at 3-month follow-up (FU). Cognitive outcome at follow-up was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), classifying 7 patients as POCD (RBANS < 80) and 7 as NO POCD. Functional connectivity between 32 brain regions, grouped in 8 resting-state networks (RSN), was estimated using mutual information (MI; static dependence) and mutual information rate (MIR; dynamic information exchange), each computed with parametric Gaussian (linear) and model-free k-nearest neighbor estimators. Pairwise connections were validated via surrogate testing, and group differences in longitudinal connectivity change ({Delta} = FU-BL) were assessed with permutation tests at global, intra- and inter-RSN scales. Graph metrics were computed on statistically thresholded weighted networks and related to RBANS using permutation-based Spearman correlations. POCD was not associated with a uniform reduction in connectivity but with a structured pattern of network reorganization. Static connectivity showed widespread alterations, particularly within higher-order associative systems, including salience, dorsal attention, and default mode networks. Dynamic connectivity did not exhibit global group differences but revealed selective, network-specific alterations in temporal information exchange. Longitudinal analyses showed that better cognitive outcomes were associated with increased global efficiency and density and reduced modularity and small-worldness, indicating a greater brain integration. In contrast, poorer outcomes were associated with increased segregation and higher betweenness centrality, suggesting greater reliance on hub-mediated communication. Linear measures captured more widespread connectivity changes, whereas nonlinear estimators revealed more selective alterations in dynamic information flow. Combining static and dynamic information measures with complementary estimators and surrogate-validated graph analysis reveals dissociable signatures of postoperative network dysfunction. POCD is characterized by impaired restoration of distributed integration and a progressive shift toward hub-dependent communication, suggesting that large-scale integrative vulnerability may constitute a candidate biomarker of cognitive resilience after cardiac surgery.