In popular vernacular, the human brain is "gray matter" - the 100 billion or so nerve cell bodies that form the basis and biology of our minds, and give the brain its characteristic pinkish-gray hue.
But white matters, too. "White matter" is myelin, a pale lipid or fat that envelopes the trillions of fibrous axons connecting neuron to neuron, making the brain a singular, functioning whole. While gray matter is typically credited with defining who we are, white matter tends to be described as mere "insulation." A professor of neurology at the University of California Los Angeles begs to differ.
"The single biggest factor that makes us human is not just our brain, but the amount of myelin in it," says Dr. George Bartzokis. "Myelin is one of evolution's latest inventions. Vertebrates have it; invertebrates don't. And humans have more than anything else."
Over a lifetime, Bartzokis says, the brain busily sheathes axons in myelin - a process called myelination that not only insulates axons from external dangers but dramatically speeds the transmission and quality of signals between nerve cells.
"Think of the Internet. Myelination makes axons more efficient. It increases bandwidth. Axons are able to do more so our brains are able to do more."
It is myelination, as much as any developmental process in our brains, he says, that determines the character and nature of a person's mind and personality.
INSULATING THE BRAINâ€™S NERVE FIBERS
In a paper published late last year in Adolescent Psychiatry, Bartzokis hypothesized that the brash, risky behavior of teens and young adults is related, at least in part, to incomplete myelination in critical thinking areas of the brain.
Beyond that, he says, incomplete or disrupted myelination contributes to or worsens autism, attention deficit/hyperactivity disorder (AD/HD) and schizophrenia. It also helps explain why younger people are more vulnerable to drug and alcohol abuse.
Some researchers, of course, remain to be convinced.
"I am wary of arguments for things that 'set us apart' from other animals," says John Allen, a biological anthropologist at the University of Southern California.
"I think by now it's a widely held belief that myelination is very important in many different ways," says Frank Haist, a project scientist in psychiatry at University of California San Diego. "But I don't think it has been proven yet that it's a distinct process, separate from other developmental processes."
But others say Bartzokis' ideas both expand and correct conventional wisdom.
"What excites me the most about George's research is the potential it has not just to challenge long-held dictums about the biological basis of a number of diseases, but to also ensure that myelinated structures, which make up more than half of the brain's volume, are accorded the significance they deserve," says Dr. Mark Walterfang, a neuropsychiatrist at Melbourne Neuropsychiatry Centre in Australia.
Imagine myelin as an ultra-thin sheet of high-cholesterol fat. The cholesterol allows myelin to wrap tightly around axons, layer upon layer like electrical tape around bare wire.
Myelination takes time. A newborn's brain has plenty of neurons but not so many axons. In the first decade or so of life, myelination occurs primarily in regions that govern essential primary functions, such as vision, hearing and motor skills, as well as basic thinking and rudimentary impulse control.
Portions of the brain responsible for more cerebral and abstract functions, such as reasoned thought, are myelinated later in the 20s, 30s and beyond.
Using MRIs and a 1907 study of postmortem brains, Bartzokis has found that maximum myelination doesn't occur, on average, until around age 50 - a finding since replicated in other studies.
"It used to be thought that brain development ended in young adulthood, but now we know (it) continues throughout life," says Paul Thompson, a UCLA neurology professor. "I think George would agree that it doesn't stop in the 50s. It's just overtaken by the negative effects of aging, so that the net effect is mental decline after that age."
The sequential process of myelination, according to Bartzokis, is profoundly significant. A baby's brain brims with neurons, with more produced every day. Around age 7 to 9, the skull becomes rigid and a fundamental transformation begins. The brain starts to selectively prune away underutilized cells and synapses to make room for the myelination process to continue. Freed resources are diverted to developing brain regions responsible for higher thinking skills, from language to abstract thought.
"Impulse control and behavior are things you have to modulate on a second by second basis," said Bartzokis. "Those inhibitory controls aren't fully functional in young people because the portions of their brains that house them - the frontal lobes - aren't myelinated until the 30s or later.
"So you can sit down with a teenager and ask them what is the right thing to do, and they'll usually come up with the right answer. But in real life, they won't (at least some of the time). Their critical cognitive systems probably aren't processing with enough immediacy yet to impact their behavior in real time. Their inhibitory circuits are not all online."
Robert F. McGivern, a San Diego State University psychologist who has studied the processing of emotional information, agrees. "If you take a very young brain, say a 3- or 4-year-old, the brain organizes itself around experience. You can train that child to learn to read very early and the brain will be well-myelinated in those parts of the brain needed for reading.
"But it will be at the expense of myelination in other areas. Feral children (isolated from human contact) are not brain-damaged. Their neural circuitry has organized and myelinated differently.
"The implication for adults is this: The process continues. As we experience things over and over, we form better connections between circuits. Well-myelinated, these circuits are more efficient and rapid. They do most of the thinking before we're consciously aware."
ABUSE AND ADDICTION
With their critical thinking skills still developing, the young are more prone to experiment with drugs and alcohol, and that abuse may impact their ability to eventually think long-term. Bartzokis explains that myelination is extremely vulnerable to damage and disruption. Oligodendrocytes - brain cells that produce cholesterol for myelin - are easily harmed or killed by certain drugs, head trauma, environmental toxins and stress hormones like cortisol.
Incomplete or impaired myelination makes addiction to drugs or alcohol more likely, suggests Bartzokis, citing a 2002 study in Biological Psychiatry that showed cocaine addicts do not seem to myelinate normally.
"If you look at (the data), you will see that the average 40- or 45-year-old cocaine addict has the same amount of white matter as the average 19-year-old."
Does poor myelination cause addiction? Bartzokis doesn't go that far, saying more research is needed. Addiction is a confounding condition with a suspected genetic component. Thompson at UCLA notes that dopamine and serotonin - neurotransmitters involved in the regulation of emotion, thought and pleasure - are altered in addicts. Abnormal myelination may play a role, he says, but it's too early to say with certainty.
Bartzokis asserts that incomplete myelination may also play a role in autism, AD/HD and schizophrenia. In these, gender looms large. Males suffer disproportionately at younger ages. Female brains myelinate earlier and faster, most notably in regions concerned with higher thinking skills.
"Look at language abilities. Girls typically have better communication skills at an earlier age than boys. The brain has to work very, very fast, and that means myelinated axons. It's not that boys aren't using their brains. It's just that the neural processes aren't equal. Using the Internet analogy, it's the difference between using a telephone line connection and a T3 line. Girls are technologically ahead until boys catch up in their 20s."
Substantial research supports this idea. A recent Israeli study found the corpus collosum - a bridge of nerve tissue connecting the brain's right and left hemispheres - was thicker in 26-week-old female fetuses than similarly aged males. Neuroimaging studies have shown that men typically process language using only the left half of their brain while women use both hemispheres.
Proving that myelin is critical to normal, healthy brain development and function is just part of the equation. The other part is figuring out what to do if this proves true. In one sense, we already know, says Bartzokis.
"Good diet, exercise, low blood pressure. These things are all good for the brain, probably more than people realize."
The role of nutrition may be particularly important. In order to build membranes - "and myelin is the ultimate membrane" - the body requires sufficient supplies of essential fatty acids found in fish oils, flaxseed, grains and nuts. But the diets of young people are notoriously poor, he says, and likely to be deficient in key nutrients.
As more becomes known, Bartzokis believes scientists will craft drugs and treatments to boost myelination. "In science, once you can measure something, you can begin to fix it."
The brain is the universe's greatest mystery, a 3-pound black box. But if Bartzokis' ideas about myelin prove right, some of the answers will be white - and matter.