Evolutionary Divergence of Structure-Function Coupling between Human and Macaque: Spatial Patterns and Transcriptomic Basis

Structural-functional coupling (SFC) provides critical insights into how the brains structural architecture constrains functional organization for supporting higher-order cognition. Investigating evolutionary differences in SFC between humans and macaques may provide new insights into the neural basis of unique human cognitive abilities. In this study, we analyzed multimodal magnetic resonance imaging data from anesthetized and awake adult rhesus macaques and adult humans to examine cross-species divergences in SFC. Moreover, we integrated transcriptomic data to elucidate the molecular mechanisms underlying evolutionary differences in SFC patterns. We find that humans and macaques exhibit distinct SFC patterns: the human brain shows high SFC in the lateral and medial prefrontal cortex, whereas macaques show high SFC in the sensorimotor cortex. Notably, language-related regions in the human lateral temporal cortex exhibit relatively low SFC. Furthermore, the human whole-brain SFC pattern and the evolutionary differences in SFC between humans and macaques are negatively correlated with cortical evolutionary expansion. By integrating human and macaque transcriptomes, we reveal that the macaque SFC specifically associated genes are primarily involved in basic physiological functions, whereas the human SFC specifically associated genes exhibit evolutionary adaptations in synaptic function, neurotransmitter secretion, and other molecular processes. Moreover, the human-specific genes showing significant overlap with Human Accelerated Regions genes were mainly enriched in cell types of astrocyte and oligodendrocyte and in diseases of schizophrenia and Alzheimers diseases. Overall, these findings advance our understanding of the intricate relationships of SFC in human and macaque brains and provide novel insights in understanding evolutionary conservation and species specificity in cognitive function and gene regulation.