Mapping Structural and Molecular Spatiotemporal Dynamics of Macaque Brain during Development and Aging

Abstract Mapping the developmental and aging trajectories of brain structures and their underlying cellular and molecular mechanisms is fundamental to understanding the organizational principles of the primate brain. Here, we systematically characterized brain structural, cellular and molecular spatiotemporal dynamics from birth to 18 years of macaques integrating multimodal magnetic resonance imaging and single-cell transcriptomics. Structurally, we found that gray matter volume, cortical surface area, and thickness of macaque brain progressively declined, which is contrary to human brain developmental patterns, but the white matter volume, microstructure, white matter and gray matter complexity steadily increased, reflecting enhanced fiber organization and network integration. Molecularly, the brain undergoes neural optimization and homeostatic maintenance during development and aging, respectively. Importantly, we linked the macroscopic structural trajectories to the molecular developmental and aging patterns to identify the cellular and molecular drivers of brain structure for the first time. In summary, these findings establish a crucial multiscale framework for understanding primate brain development and aging and shed new light on the divergent evolution between macaques and humans. Our work provides a comprehensive and integrated resource that bridges molecular, structural and network-level scales in primate neuroscience.