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

We integrated 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. Brain circuitry was modeled as a directed connectome, where asymmetric pathways capture forward neuronal signal flow. Using a common cross-species atlas as a scaffold, we introduced a path efficiency metric balancing projection strength against axonal length and applied shortest-path algorithms to quantify inter-regional influence. This framework revealed conserved and divergent organization. The entorhinal-hippocampal projection remained the most efficient in all species, underscoring memory-circuit preservation. In humans, anterior insula-superior temporal paths gained efficiency, strengthening a temporal-insula-frontal circuit while olfactory pathways ranked lower. Macaques showed peak efficiencies in inferior temporal outflows, whereas marmosets maintained high olfactory influence. Together, these results establish a scalable framework for directed connectomics and show how conserved and lineage-specific circuits shaped association and sensory systems.