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The Brain's White Matter Hubs Take Center Stage

White matter damage may affect cognitive outcomes more than gray matter damage.

Key points

  • White matter supports communication between gray matter areas across the brain.
  • Recent research has found associations between measures of white matter and mental illness.
  • A new study suggests that damage to highly connected white matter areas may affect cognition more than comparable gray matter damage.
 Gerd Altmann/Pixabay
Much like analog-era communication lines made it possible for brick-and-mortar hubs in different cities to send cable messages around the world, white matter tracts send messages between gray matter brain regions within the cranial globe.
Source: Gerd Altmann/Pixabay

White matter consists of bundled axons covered in a fatty sheath of whitish-looking myelin. It facilitates communication between various gray matter regions in the central nervous system. Although gray matter is often treated like a rock star and white matter almost always seems to be playing second fiddle, accumulating evidence suggests that both deserve equal billing.

When my late neuroscientist father, Richard Bergland (1932-2007), was teaching me about the architecture of the brain as a kid in the 1970s, he made the analogy that white matter was like the fiber-optic communication networks (first introduced in 1977) that allowed multinational corporations to send messages between different "gray matter" hubs in cities around the world.

White Matter Carries Messages Within and Between the Brain's Hemispheres

Along this line, the brick-and-mortar buildings that housed a company's branch locations in the northern and southern hemispheres were akin to the gray matter structures housed within all four brain hemispheres in the cerebrum and cerebellum. For example, white matter functional connectivity between different brain regions within the cerebrum and cerebellum made cerebro-cerebellar inter-hemispheric communication possible, much like fiber-optic networks made international telecommunications possible from Sydney to New York or London to Buenos Aires.

Continuing with this metaphor, Dad posited that even when the home office of a company like American Express with global headquarters in a state-of-the-art Manhattan skyscraper was communicating with local branches in places like Athens or Cairo (which might be housed in ancient or damaged structures), if the communication lines stayed strong, messages could be received loud and clear regardless of the branch office's architectural structure. In the brain, this Amex scenario would be analogous to robust white matter tracts maintaining cognitive functions despite damaged or atrophied gray matter structures.

In his book, The Fabric of Mind (1986), my father presents white matter and gray matter as a dynamic duo that works in tandem to optimize human cognition. Because he was also a neurosurgeon, Dad had observed a young patient with damage to a particular gray matter region whose brain seemed to rewire its connectivity in a way that shifted a particular brain function from one region to another. Remarkably, this patient—and others who seemed to rewire their white matter communication networks via neuroplasticity—didn't show marked signs of cognitive impairment.

Although it was just an educated guess, my father speculated that white matter networks might be able to compensate for gray matter damage by rerouting their communication lines. Therefore, although gray matter almost always got top billing, my father viewed white matter as an underappreciated "star player" and passed this view on to me.

In recent years, a variety of studies have put white matter in the spotlight. There appears to be a growing consensus that white matter and gray matter are both important when it comes to offsetting cognitive decline or optimizing the structure and functional connectivity of the whole brain. Additionally, structural alterations and white matter microstructural differences have recently been associated with various mental disorders.

The Cognitive Impact of Damage to Critical White Matter Regions

This week, a new study of two cohorts ( N = 504) of patients with focal brain lesions reports that "lesions involving densely connected white matter regions were associated with impaired cognitive performance to a greater extent than lesions of highly connected gray matter regions." These findings ( Reber et al., 2021) were published on May 3 in Proceedings of the National Academy of Sciences .

According to Justin Reber and co-authors, "these findings highlight the critical role of densely connected white matter regions in supporting cognition, which helps to explain interindividual differences in cognitive outcomes following brain damage."

In discussing potential future research directions, the authors state: "Our findings indicate that [white matter] edge density can be used to predict the likelihood of cognitive impairments, above and beyond the predictive utility of well-established predictors like [gray matter] lesion volume. As such, this information could be incorporated into prognostic tools to more accurately predict cognitive outcomes after an acquired brain lesion, helping to inform treatment and rehabilitation plans for patients with focal brain damage."


Justin Reber, Kai Hwang, Mark Bowren, Joel Brussb, Pratik Mukherjeed, Daniel Tranel, and Aaron D. Boes. "Cognitive Impairment After Focal Brain Lesions Is Better Predicted by Damage to Structural Than Functional Network Hubs." PNAS (First published: May 03, 2021) DOI: 10.1073/pnas.2018784118