# Cortical white matter: no longer a silent partner

## TL;DR

This paper argues that cortical white matter should not be overlooked in brain studies, as it has its own complex organization and plays an active role in brain function.

## Contribution

The paper presents a new perspective on cortical white matter by emphasizing its multi-scale organization and active role in brain processes.

## Key findings

- Cortical white matter has a complex organization similar to gray matter.
- Axons in white matter are active participants in brain processes.
- Recent research suggests a shift toward a more holistic study of white matter.

## Abstract

This takes the position that the cell-sparse cortical white matter (WM) of gyrencephalic brains has too long held a secondary place in neuroanatomical investigations of cell-dense gray matter (GM) regions. This is unjustified and even problematic because WM, like GM, has its own subcellular, cellular, and supracellular multi-scale organization. Axons are not passive cables or wires, but engage in multiple processes, some in cooperation with neurons in the GM and, as increasingly recognized, also inter- and intra-axonal. In five sections of this review, we revisit traditional assumptions about WM organization and touch on recent results regarding: the axonal cytoskeleton and myelination, neuroanatomical approaches to global WM organization, open issues about “endpoints” (i.e., origin and termination of axon bundles), and orderly vs. “scrambled” topographies. There has been significant research progress at all spatial scales, and there is good reason to anticipate a more holistic approach in the next stages that will bring WM investigations more in line with the integrative approaches already customary in GM investigations.