Mild exogenous inflammation reduces dynamic small-world topology in resting-state brain networks of healthy males

Systemic inflammation is increasingly recognised as a key modulator of brain function, yet its impact on large-scale brain network topology remains incompletely understood. In particular, it is unclear whether inflammation alters the balance between functional segregation and integration, as captured by small-world organisation, and whether such effects are better detected using dynamic rather than static connectivity analyses. In this study, we conducted a secondary analysis of a previously collected dataset to examine the effects of experimentally induced inflammation on static and dynamic small-world topology using resting-state fMRI and graph-theoretical methods. Eighteen healthy male participants completed a double-blind, placebo-controlled, randomised crossover trial involving typhoid vaccination, a well-established model of low-grade systemic inflammation. Small-worldness was quantified across a fixed density range for both static and dynamic functional connectivity. No significant differences were observed in static small-worldness between conditions. In contrast, dynamic analyses revealed a significant reduction in mean small-worldness following vaccination. This effect was primarily driven by reduced clustering coefficient, with no change in characteristic path length, indicating a selective alteration in local segregation while preserving global integration. Dynamic state analysis identified two recurring connectivity states with distinct topological profiles. Although differences in fractional occupancy and dwell time were not statistically significant, participants showed a consistent tendency to spend less time in the high small-worldness state following inflammation. These preliminary findings indicate that inflammation modulates the temporal organisation of brain networks in ways not detectable using static approaches and are consistent with a metabolically efficient reconfiguration of network topology under inflammatory challenge.