The Chimpanzee Brainnetome Atlas reveals distinct connectivity and gene expression profiles relative to humans.

Abstract

Chimpanzees (Pan troglodytes) are one of humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occurred along the human lineage. However, such comparisons are hindered by the absence of cross-species brain atlases established within the same framework. To address this gap, we developed the Chimpanzee Brainnetome Atlas (ChimpBNA) using a connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns between the two species across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex. These differences deviate sharply from the pattern of cortical expansion observed when comparing humans to chimpanzees, highlighting more complex and nuanced connectivity changes in brain evolution than previously recognized. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes highly expressed in regions of divergent connectivities were enriched in cell types crucial for cortical projection circuits and synapse formation, whose pronounced differences in expression patterns hint at genetic influences on neural circuit development, function, and evolution. Our study provides a fine-scale chimpanzee brain atlas and highlights the chimpanzee-human connectivity divergence in a rigorous and comparative manner. In addition, these results suggest potential gene expression correlates for species-specific differences by linking neuroimaging and genetic data, offering insights into the evolution of human-unique cognitive capabilities.