Mapping Human Brain Pathways: Challenges and Opportunities in the Integration of Scales

The human brain is composed of a complex web of pathways. Diffusion magnetic resonance (MR) tractography is a neuroimaging technique that relies on the principle of diffusion to reconstruct brain pathways. Its tractography is broadly applicable to a range of problems as it is amenable for study in individuals of any age and from any species. However, it is well known that this technique can generate biologically implausible pathways, especially in regions of the brain where multiple fibers cross. This review highlights potential misconnections in two cortico-cortical association pathways with a focus on the aslant tract and inferior frontal occipital fasciculus. The lack of alternative methods to validate observations from diffusion MR tractography means there is a need to develop new integrative approaches to trace human brain pathways. This review discusses integrative approaches in neuroimaging, anatomical, and transcriptional variation as having much potential to trace the evolution of human brain pathways.