Mapping Connections in Humans and Non-Human Primates. Aspirations and Challenges for Diffusion Imaging.

Systematic mapping of long-distance pathways in the human brain (the "macro-connectome") represents a grand challenge for the coming century. Diffusion imaging and resting-state functional MRI represent the two main modalities for examining the macro-connectome in vivo. However, the fidelity with which these two complementary techniques reflect true connectional anatomy is yet to be thoroughly assessed. We review a set of neuroanatomical observations in the macaque monkey that frame our understanding of brain connectivity for primates, including humans. We then describe approaches used by the Human Connectome Project (HCP) to improve data acquisition, analysis, and visualization for diffusion and functional imaging. We also analyze methodological biases and limitations in diffusion imaging and tractography, and discuss options for reducing their impact. © 2014 Elsevier Inc. All rights reserved.