Cross-species brain circuitry from diffusion MRI tractography and mouse viral tracing

We integrate tracer-derived projection polarity from ∼1,200 mouse injections with species-specific diffusion MRI (dMRI) tractography to construct directed connectomes for mouse, marmoset, rhesus macaque, and human. We model brain circuitry as a directed connectome, in which asymmetric pathways capture the forward flow of neuronal signals. Using a common cross-species atlas as a scaffold, we introduced a multi-objective path efficiency metric that weighs projection strength against axonal length and applied directed shortest-path algorithms to quantify inter-regional influence. This framework revealed both conserved and divergent organization: the entorhinal-hippocampal projection remained the most efficient in all species, while humans exhibited strengthened temporal-insula-frontal circuits and reduced olfactory influence, rhesus macaques showed peak efficiencies in inferior temporal outflows, and marmosets maintained high olfactory influence. Together, these results establish a scalable approach for constructing directed connectomes across species and demonstrate how conserved and lineage-specific circuits jointly shaped association and sensory systems.