Local Interaction Rules Drive Global Organization of the Human Connectome.
INTRODUCTION The human connectome exhibits nontrivial large-scale organization despite emerging from decentralized local biological interactions. Most existing generative models reproduce connectomic features through global optimization principles, predefined wiring targets, or developmental templates, leaving unresolved which properties arise from locality alone and which require additional nonlocal mechanisms. METHODS We implemented a simulation framework showing that global coherence can emerge from local compatibility constraints. Networks were generated exclusively through bounded spatial interactions, probabilistic local edge formation, and suppression of incompatible configurations, without global objectives, target topologies, or long-range coordination. Simulated ensembles were analyzed using graph-theoretical metrics, scaling relationships, and rule-based structural classification relative to published reference values of human connectome descriptors. RESULTS Simulations consistently generated mesoscopic organization characterized by high clustering, modular structure, motif enrichment, and strong short-range connectivity bias. Degree distributions were broad and right-skewed, while edge-length distributions showed pronounced spatial localization. In contrast, several higher-order integrative properties were not reproduced, including empirical connectivity scale, rich-club organization, and long-range hub-to-hub connectivity. Although global metrics displayed substantial quantitative divergence from reported empirical values, several structural regimes and scaling relationships were preserved across parameter ranges. DISCUSSION Our results distinguish connectome properties structurally compatible with local compatibility constraints from those underdetermined under locality alone. We provide a diagnostic framework designed to isolate the explanatory contribution of local interaction rules to connectome organization through simulations that identify which structural properties emerge directly from locality and which require additional mechanisms beyond local constraints.