One Big Reason Most Brain Research Only Tells Half the Story

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"We don't know exactly what the cerebellum is doing, but whatever it's doing, it's doing a lot of it. [...] White matter tracts are like fiber-optic cables that send communication signals between gray matter hubs in different brain regions." —Richard Bergland, 20th-century neuroscientist, neurosurgeon, and author of The Fabric of Mind.

Since the aughts, I've been on the lookout for neuroscience-based research that puts white matter and our oft-overlooked cerebellum in the spotlight. In this post, I'll report on some recently published white matter research and explain why an accompanying Perspective piece (Filley, 2021) that describes "corticocentric myopia" shed light on an "up brain-down brain" functional connectivity map of both cerebral and cerebellar hemispheres that I drew in 2009.

Genetic Variants Influence How White Matter Tracts Connect Gray Matter in Different Brain Regions

This morning, I was excited to learn about a pioneering new genome-wide association study (GWAS) that identifies how common genetic variations influence white matter microstructure in ways that appear to affect human behavior and complex traits ranging from cognitive functions to psychiatric disease. These findings (Zhao et al., 2021) were published on June 18 in the peer-reviewed journal Science.

"Brain regions communicate with each other through tracts of myelinated axons, commonly referred to as white matter. We identified common genetic variants influencing white matter microstructure using diffusion magnetic resonance imaging of 43,802 individuals," Zhao et al. explain in their paper's abstract. "We identified 151 genomic regions associated with white matter microstructure."

"Moreover, we uncovered genetic relationships between white matter and various clinical endpoints, such as stroke, major depressive disorder, schizophrenia, and attention deficit hyperactivity disorder," the authors note. "The targets of many drugs commonly used for disabling cognitive disorders have genetic associations with white matter, which suggests that the neuropharmacology of many disorders can potentially be improved by studying how these medications work in the brain white matter."

In his accompanying Perspective piece, published in the same issue of Science, Christopher Filley of CU Medicine's department of neurology writes, "On page 1304 of this issue, Zhao et al. present compelling evidence for the importance of white matter by demonstrating genetic influences on structural connectivity that invoke a host of provocative clinical implications."

What struck me most about Filley's "White Matter and Human Behavior" commentary was his observation that "one of the most enduring themes in human neuroscience is the association of higher brain functions with gray matter. In particular, the cerebral cortex—the gray matter of the brain's surface—has been the primary focus of decades of work aiming to understand the neurobiological basis of cognition and emotion."

"Yet, the cerebral cortex is only a few millimeters thick, so the relative neglect of the rest of the brain below the cortex has prompted the term 'corticocentric myopia,'" Filley adds. "Other regions relevant to behavior include the deep gray matter of the basal ganglia and thalamus, the brainstem and cerebellum, and the white matter that interconnects all of these structures."

In a 2009 paper, "Corticocentric Myopia: Old Bias in New Cognitive Sciences," Josef Parvizi of Stanford University writes, "Traditionally, the cerebral cortex is seen to have the most important role in 'higher' functions of the brain, such as cognition and behavioral regulation, whereas subcortical structures are considered to have subservient or no roles in these functions."

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In his paper's abstract, Parvizi sums up: "The aim of this article is to suggest that the 'corticocentric' view of the human brain is also a myopic view because it does not let us see that the 'higher' functions of the brain might, in fact, depend on the integrity of its 'lower' structures."

This hand-drawn brain map illustrates how white matter tracts facilitate inter-hemispheric communication between cortical and subcortical gray matter hubs in the cerebrum and cerebellum.

Source: Photo and illustration by Christopher Bergland (circa 2009)

Reexamining My "Super 8" Brain Map Through the Lens of Corticocentric Myopia

My late neuroscientist father, Richard Bergland (1932-2007), dedicated the later years of his life trying to disrupt the status quo and convince his research colleagues to look beyond the cerebral cortices' gray matter. Although he never used the term "corticocentric myopia," this sums up exactly what my dad was fighting against when he urged me to put the cerebellum, white matter, and functional connectivity in the spotlight while writing The Athlete's Way (2007).

When my father and I created our split-brain model, "up brain-down brain," the primary goal was to bring the cerebellum out of the shadows and show how the cerebrum and our so-called "little brain" work in tandem to optimize whole-brain functions. Colloquially, Dad and I would refer to the cerebral cortex as "Godzilla" and the cerebellum as an underappreciated "mighty mouse."

Earlier this year, I wrote a blog post, "My Decades-Long Quest to Decode a Quirky 'Super 8' Brain Map," which details my ongoing efforts to understand how optimizing the white matter connectivity between all four brain hemispheres facilitates peak performance in life and sport.

With Father's Day this weekend, it's gratifying to see a Perspective piece in the latest issue of Science discussing issues related to "corticocentric myopia" and unearthing white matter discoveries that my dad would've loved to see brought to light during his lifetime. Better late than never!