BRAIN SCIENCE White Matter Matters Although scientists have long regarded the brain’s white matter as passive infrastructure, new work shows that it actively affects learning and mental illness • • • By R. Douglas Fields magine if we could peek through the skull entists are now realizing that we have under- KEY CONCEPTS to see what makes one brain smarter than estimated the importance of white matter in ■ White matter, long thought I another. Or to discover whether hidden the proper transfer of information among brain to be passive tissue, active- traits might be driving a person’s schizophrenia regions. New studies show that the extent of ly affects how the brain or dyslexia. A new kind of imaging technique white matter varies in people who have differ- learns and dysfunctions. is helping scientists observe such evidence, and ent mental experiences or who have certain ■ Although gray matter it is revealing a surprise: intelligence, and a dysfunctions. It also changes within one per- (composed of neurons) variety of mental syndromes, may be influenced son’s brain as he or she learns or practices a does the brain’s thinking by tracts within the brain made exclusively of skill such as playing the piano. Even though the and calculating, white white matter. neurons in gray matter execute mental and matter (composed of my- Gray matter, the stuff between your ears physical activities, the functioning of white elin-coated axons) con- your teachers chided you about, is where men- matter may be just as critical to how people trols the signals that neu- tal computation takes place and memories are master mental and social skills, as well as to rons share, coordinating stored. This cortex is the “topsoil” of the brain; why it is hard for old dogs to learn new tricks. how well brain regions it is composed of densely packed neuronal cell work together. bodies—the decision-making parts of nerve More with Mastery ■ A new type of magnetic cells, or neurons. Underneath it, however, is a The myelin that gives white matter its color has resonance technology, bedrock of “white matter” that fills nearly half always posed mysteries. For more than a centu- called diffusion tensor im- of the human brain—a far larger percentage ry scientists looked at neurons through their aging (DTI), has for the than found in the brains of other animals. microscopes and saw long fibers, the axons, first time shown white matter in action, revealing White matter is composed of millions of com- extending from a neuronal cell body to a neigh- its underappreciated role. munications cables, each one containing a long, boring one, like an outstretched, elongated fin- individual wire, or axon, coated with a white, ger. Each axon was found to be coated with a ■ Myelin is only partially fatty substance called myelin. Like the trunk thick crystalline gel. Anatomists surmised that formed at birth and gradu- lines that connect telephones in different parts the fatty covering must insulate axons like rub- ally develops in different regions throughout our of a country, this white cabling connects neu- ber sheathing along a copper wire. Strangely, 20s. The timing of growth rons in one region of the brain with those in however, many axons, especially the smaller fil- and degree of completion other regions. aments, were not coated at all. And even along can affect learning, self- For decades neuroscientists exhibited little insulated fibers, gaps in the insulation appeared control (and why teenag- interest in white matter. They considered the every millimeter or so. The bare spots came to ers may lack it), and men- myelin to be mere insulation and the cables in- be known as nodes of Ranvier, after French tal illnesses such as side it little more than passive passageways. anatomist Louis-Antoine Ranvier, who first schizophrenia, autism and Theories about learning, memory and psychi- described them. even pathological lying. atric disorders centered on molecular action in- Modern investigation has revealed that nerve —The Editors side the neurons and at the famous synapses— impulses race down axons on the order of 100 the tiny contact points between them. But sci- times faster when they are coated with myelin— 54 SCIENTIFIC AMERICAN Marc h 20 0 8 © 2008 SCIENTIFIC AMERICAN, INC. White Matter Matters SCULPTURE depicts overhead view of brain’s cortex (copper) SCULPTUREBYMARGIE MCDONALD, PHOTOGRAPHED BYFRANK ROSS and white matter core. www.SciAm.com SCIENTIFIC AMERICAN 55 © 2008 SCIENTIFIC AMERICAN, INC. and that myelin is laid on axons somewhat like “know” whether 10 or 100 layers of insulation electrical tape, wrapped up to 150 times be- Myelin is laid are required to create the proper thickness on tween every node. The substance is manufac- axons of different diameters. But recently biol- tured in sheets by two types of glial cells. These down until age ogist Klaus-Armin Nave of the Max Planck In- cells are not neurons, but they are prevalent in 25 or so, one stitute for Experimental Medicine in Göttingen, the brain and nervous system [see “The Other Germany, discovered that Schwann cells detect Half of the Brain,” by R. Douglas Fields; Sci- reason teenagers a protein called neuregulin that coats axons, entific American, April 2004]. An octopus- do not have and if the amount of this protein is augmented shaped glial cell called an oligodendrocyte does or inhibited, the Schwann cell will wrap more the wrapping. Electrical signals, unable to leak adult decision- or fewer sheets of myelin around the axon. In- out through the sheath, jump swiftly down the making abilities. terestingly, many people who suffer bipolar dis- axon from node to node. In nerves outside the order or schizophrenia have a defect in the gene brain and spinal cord, a sausage-shaped glial that regulates production of this protein. cell called a Schwann cell forms myelin. The wrapping occurs at different ages. My- Without myelin, the signal leaks and dissi- elin is prevalent only in a few brain regions at pates. For maximum conduction velocity, the birth, expands in spurts and is not fully laid un- insulation thickness must be strictly propor- til age 25 or 30 in certain places. Myelination tional to the diameter of the fiber inside. The generally proceeds in a wave from the back of optimal ratio of bare axon diameter divided by the cerebral cortex (shirt collar) to its front the total fiber diameter (including the myelin) is (forehead) as we grow into adulthood. The 0.6. We have no idea how oligodendrocytes frontal lobes are the last places where myelina- [BASICS] WHAT IS WHITE MATTER? White matter fills nearly half the brain. It consists of millions of cables (white) that connect individual neurons (gray matter) in different brain regions, like trunk lines connecting telephones across a country. White matter Gray matter Cortex Cingulum Corpus callosum Cingulum Corpus callosum ) Axon tractography Myelin cingulum ( Neuron CardiffUniversity Corpus callosum, a mass of white matter );DEREK JONES cables, connects the brain’s left and right hemispheres. On either side, the illustration cables extend up and outward toward the cortex, creating a structure called the cin- Each cable leads from a neuron in gulum. A new form of imaging, DTI tractog- one region to a neuron elsewhere. A cable is raphy, can chart the actual cable pathways. an axon insulated with milky-white myelin. JENCHRISTIANSEN ( 56 SCIENTIFIC AMERICAN Marc h 20 0 8 © 2008 SCIENTIFIC AMERICAN, INC. CONVENTIONAL MRI machine (top) can roughly depict white matter (bottom left, white areas). But a new MRI process called DTI shows structure in greater detail (bottom right); red and yellow indicate more highly organized white matter. tion occurs. These regions are responsible for higher-level reasoning, planning and judg- ment—skills that only come with experience. Researchers have speculated that skimpy fore- brain myelin is one reason that teenagers do not have adult decision-making abilities. Such ob- servations suggest that myelin is important to intelligence. Presumably the brain does not finish wrap- ping human axons until early adulthood be- Forehead cause, throughout that time, axons continue to grow, gain new branches and trim others in re- sponse to experience. Once axons are myelin- ) ated, the changes they can undergo become more limited. Still, for a long time a question re- mained: Is myelin formation totally pro- black-and-whitescan grammed, or do our life experiences alter the ( degree of wrapping and thus how well we learn? Does myelin actually build cognitive ability, or is cognition simply limited in regions where it has not yet formed? Piano virtuoso Fredrik Ullén decided to find out. Ullén also happens to be an associate pro- fessor at the Stockholm Brain Institute in Swe- UlsterMedical and Surgical Specialists den. In 2005 he and his colleagues used a new Back brain-scanning technology called diffusion ten- sor imaging (DTI) to investigate the brains of He also found that the more hours a day a );JOE GALLIVAN professional pianists. DTI is done with the same musician had practiced over time, the stronger colorscan kind of magnetic resonance imaging machines the DTI signals were in these white matter found in hospitals but involves a different type tracts; the axons were more heavily myelinated of magnetic field and different algorithms to or tightly packed. Of course, the axons could create the many brain-image slices that are as- simply have expanded, requiring more myelin sembled into a three-dimensional picture. The to maintain the optimal 0.6 ratio. Without per- [THE AUTHOR] slices display the vectors (mathematically de- forming an autopsy, the question remains open. fined as tensors) of water that diffuses in tissue. The discovery is important, however, because it In gray matter the DTI signals are low because shows that when learning a complex skill, no- );ZEPHYR/ PHOTO RESEARCHERS, INC.