AbstractThe human brain structural network is thought to be shaped by the optimal trade-off between cost and efficiency. However, most studies on this problem have focused on only the trade-off between cost and global efficiency (i.e., integration) and have overlooked the efficiency of segregated processing (i.e., segregation), which is essential for specialized information processing. Direct evidence on how trade-offs among cost, integration, and segregation shape the human brain network remains lacking. Here, adopting local efficiency and modularity as segregation factors, we used a multiobjective evolutionary algorithm to investigate this problem. We defined three trade-off models, which represented trade-offs between cost and integration (Dual-factor model), and trade-offs among cost, integration, and segregation (local efficiency or modularity; Tri-factor model), respectively. Among these, synthetic networks with optimal trade-off among cost, integration, and modularity (Tri-factor model [Q]) showed the best performance. They had a high recovery rate of structural connections and optimal performance in most network features, especially in segregated processing capacity and network robustness. Morphospace of this trade-off model could further capture the variation of individual behavioral/demographic characteristics in a domain-specific manner. Overall, our results highlight the importance of modularity in the formation of the human brain structural network and provide new insights into the original cost-efficiency trade-off hypothesis.