Evolutionary Reorganization of the Self-Processing Network Across Primates

Understanding the evolutionary origins of the structural substrates underlying self-processing is central to elucidating the neural basis of human cognition. Although self-related behaviors differ markedly across primates, the extent to which the underlying neural architecture is conserved or reorganized remains unclear. Here, we investigated shared and species-specific characteristics of the self-processing network (SPN) across humans (n = 46, 19 males), chimpanzees (n = 46, 18 males), and macaques (n = 43, 22 males) using a comparative connectomic framework. We mapped a meta-analysis-derived human SPN onto nonhuman primates within a shared homologous connectivity space defined by conserved white-matter tracts. We compared local microstructural properties and gene expression signatures between humans and macaques, and further included chimpanzees as an intermediate evolutionary reference for large-scale structural connectivity. SPN regions exhibited highly similar myelin-sensitive contrast profiles in humans and macaques, accompanied by shared expression patterns of related genes, which were also enriched for human-accelerated brain genes. Large-scale connectivity revealed pronounced species differences, with chimpanzees occupying an intermediate position between humans and macaques. Importantly, evolutionary modifications of the SPN were domain-specific: Interoceptive-processing subnetworks showed greater similarity between macaques and chimpanzees; Exteroceptive-processing subnetworks showed closer correspondence between chimpanzees and humans; and Mental-self-processing subnetworks exhibited greater interspecies differentiation. Moreover, these changes were accompanied by a progressive reorganization of network hubs from insular regions in macaques to cingulate regions in humans. Together, these findings reveal a scale-dependent evolutionary organization of SPN structural substrates and provide a framework for understanding the conservation and reorganization of self-processing architectures across primates.Significance Statement Self is a central construct in cognition, yet its neural evolution remains poorly understood. By comparing local biological features between humans and macaques and using chimpanzees as an intermediate reference for structural connectivity, this study reveals a scale-dependent dissociation in the reorganization of self-processing network (SPN) structural substrates across primates. Local microstructural and transcriptional features of the SPN are highly conserved between humans and macaques, whereas large-scale network architecture is selectively and nonuniformly reorganized. This reorganization follows domain-specific patterns that diverge from whole-brain evolutionary trends and is accompanied by systematic shifts in network hub organization. These findings provide a framework for understanding how neural architectures associated with human self-processing may have emerged from conserved primate brain systems.