Evolution of Brain Connections: Integrating Diffusion MR Tractography With Gene Expression Highlights Increased Corticocortical Projections in Primates

<jats:title>Abstract</jats:title> <jats:p>Diffusion MR tractography permits investigating the 3D structure of cortical pathways as interwoven paths across the entire brain. We use high-resolution scans from diffusion spectrum imaging and high angular resolution diffusion imaging to investigate the evolution of cortical pathways within the euarchontoglire (i.e., primates, rodents) lineage. More specifically, we compare cortical fiber pathways between macaques (Macaca mulatta), marmosets (Callithrix jachus), and rodents (mice, Mus musculus). We integrate these observations with comparative analyses of Neurofilament heavy polypeptide (NEFH) expression across the cortex of mice and primates. We chose these species because their phylogenetic position serves to trace the early evolutionary history of the human brain. Our comparative analysis from diffusion MR tractography, cortical white matter scaling, and NEFH expression demonstrates that the examined primates deviate from mice in possessing increased long-range cross-cortical projections, many of which course across the anterior to posterior axis of the cortex. Our study shows that integrating gene expression data with diffusion MR data is an effective approach in identifying variation in connectivity patterns between species. The expansion of corticocortical pathways and increased anterior to posterior cortical integration can be traced back to an extension of neurogenetic schedules during development in primates.</jats:p>