Reconstructing the human brain's wiring diagram from axons up.

Area of Science:

• Neuroscience
• Connectomics
• Brain Mapping

Background:

• Long-range axonal connections are crucial for human brain communication.
• Current understanding of the human brain's wiring diagram is limited by technological challenges.
• Mesoscale mapping (groups of neurons and axons) is a promising frontier.

Purpose of the Study:

• To review the challenges and importance of generating human brain wiring diagrams.
• To propose an axon-centric, multimodal approach for building a human mesoscale connectome.
• To discuss the potential utility of a human connectome for research and clinical applications.

Main Methods:

• Reviewing existing technological challenges in brain mapping.
• Discussing innovations in microscopy for mesoscale connectomics.
• Proposing a multimodal, multi-species, axon-centric strategy.
• Focusing on axon origins and terminations for connectivity reconstruction.

Main Results:

• Technological hurdles have historically limited human connectome mapping.
• Recent microscopy advances enable mesoscale connectivity mapping.
• An axon-centric approach is vital for reconstructing connectivity across resolutions.

Conclusions:

• Building a human mesoscale connectome is an important, achievable goal.
• A multimodal, multi-species, axon-centric strategy is recommended.
• An exemplar human connectome could significantly benefit clinical and research endeavors.