Sarah Mellnik was four years old when her doctors discovered the striking anomaly in her brain. She was missing the massive connective bridge that ordinarily unites the brain's two hemispheres. This malformation can delay the development of verbal and motor skills, among other abilities. Today, however, Mellnik is a gregarious and active 29-year-old. She not only walks, she volunteers as an assistant dance teacher.

These milestones did not come easily. In high school she endured other students' taunts, disbelieving teachers and difficulties with class work. In spite of her struggles, Mellnik earned her high school diploma in 2000. Her mantra, which she repeats to herself and others like her, is “Never give up.”

When brain development goes awry, as in Mellnik's case, a structure called the corpus callosum can grow in only partially or not at all. In a typical brain the 200 million nerve fibers of the corpus callosum serve as a high-speed data line that shuttles neural messages between hemispheres. Individuals with this disorder, called agenesis of the corpus callosum, often have cognitive deficits, ranging from autismlike symptoms to mild learning difficulties.

The fact that the brain can cope at all without its largest connective pathway reveals its remarkable dynamism. The brain's self-tuning in the absence of the corpus callosum exposes some of the rules that govern neural plasticity and repair. These findings could also help us better understand diverse conditions, including autism and schizophrenia, that may arise in part from a malformed corpus callosum.

Gaps in the Brain's Bridge

This set of nerve fibers is perhaps best known for its role in one of the most famous experiments in neuroscience. In the 1960s Michael S. Gazzaniga and Richard Sperry of the California Institute of Technology studied a group of people with epilepsy whose corpus callosum had been severed to stop the spread of seizures through the brain. The surgery quelled the seizures, but it also brought on cognitive problems.

Sperry and Gazzaniga discovered these disabilities by asking subjects to train their eyes on a dot in the middle of a screen while images appeared to the right or left of the dot. These so-called split-brain patients could identify the pictures without hesitation when they appeared on the right side but not when they showed up on the left.

As scientists now know, information entering each eye travels to the opposite brain hemisphere for processing. In most people, only the left hemisphere is dominant for verbal tasks. When visual input traveled to a patient's right hemisphere, that signal could not then cross the brain to produce the words needed to identify the images. This discovery, which confirmed how the hemispheres specialize in processes, garnered Sperry the 1981 Nobel Prize in medicine. The work also illustrates the vital role of the corpus callosum in a normally functioning brain. [For more on split-brain patients, see “Spheres of Influence,” by Michael S. Gazzaniga; Scientific American Mind, June/July 2008.]

Typically this 10-centimeter-long bundle of neural fibers begins to grow during the 11th week of pregnancy and continues to develop through adolescence. Every fiber is a neuron's axon, the long, spindly protrusion that connects brain cells. Chemical messengers guide the first nerve fibers, called pioneer axons, from one hemisphere to a terminus in the opposite hemisphere. Other axons follow the pioneers until many millions of threads of nervous tissue weave the two hemispheres together. These links play a role in multiple essential functions, including attention and memory.

Life experiences can alter the corpus callosum. For example, in 2008 Harvard Medical School neuroscientist Gottfried Schlaug found that musicians who began studying an instrument before age seven have a larger corpus callosum than nonmusicians, as well as bulked-up portions of the auditory and motor areas of the brain. A difficult childhood can have the opposite effect: a 2004 study led by Martin Teicher, also at Harvard, showed that children who were neglected or abused had a corpus callosum that was 17 percent smaller than that of healthy children.

In roughly one in 4,000 infants, however, the corpus callosum fails to form, leading to speech and motor delays in as many as 80 percent of cases. One prominent example is the savant Kim Peek, whose astonishing feats of memory inspired the 1988 movie Rain Man. Often genetics are to blame, but environmental factors can also take a toll: almost 7 percent of babies with fetal alcohol syndrome develop an abnormal corpus callosum.

Individuals lacking this structure also tend to be born with other brain malformations. As a result, some people exhibit severe handicaps, such as seizures and mental retardation, whereas others possess ordinary IQs. Roughly a third of individuals without a corpus callosum meet the criteria for an autism spectrum disorder.

Because the outcomes vary so widely, those with a malformed corpus callosum may go undiagnosed for years. For instance, Joseph Galbraith learned only at age 45 that he had the disorder. “All of my life I knew that I was not connecting the dots like other people,” he says. “It seemed like 40 years of shame and guilt started melting away.”

The Plastic Brain

The cognitive deficits that accompany agenesis of the corpus callosum differ from those seen in Sperry and Gazzaniga's experiments in telling ways. In 1991 neuropsychologist Maryse Lassonde and her colleagues at the University of Montreal recruited three groups of people: those who had their corpus callosum fully severed as an adult, individuals who underwent the procedure in childhood and subjects who never developed one at all. Lassonde asked her blindfolded participants to identify objects in either their left or right hand by touch. As with visual input from the eyes traveling across hemispheres, information from the right hand is processed in the left hemisphere, and vice versa.

What they discovered was startling. Only split-brain patients who had had these central fibers severed as adults could not name the objects in their left hand. Subjects who had lived most of their life without a complete structure had no trouble with the task. Somehow the young brain could compensate.

Scientists are only now learning how extensive that compensation is. In 2011 neuroimaging specialist J. Mike Tyszka and his colleagues at Caltech observed the neural activity patterns of eight people who had never grown a corpus callosum. These individuals had normal IQs and no other brain abnormalities. When the subjects lay idle in a brain scanner, Tyszka expected to see the two hemispheres operating independently of each other. To his surprise, the two halves' activation patterns were both synchronized and symmetric. In all, the patterns looked very much like those of normal brains.

In my own research my colleagues and I have learned that people with a malformed corpus callosum but no other brain defects can relay complex information between hemispheres, further evidence that the brain must depend on alternative pathways. This work dovetails with the idea that during critical growth periods the young brain can respond to congenital defects, injuries and surgical procedures by forming new connections. The ability of a brain during childhood to find different wiring patterns reveals its extraordinary malleability and plasticity. The question now is how exactly messages can traverse the brain when the backbone of its communication network is shut down.

Rebuilding Connections

One hypothesis is that the brain builds up much smaller bridges between hemispheres. In my study, for example, four of our five subjects had an unusually large anterior commissure, a bundle of fibers that is normally about a tenth the size of the corpus callosum. Another possibility is that neurons rely on stunted structures known as Probst bundles, which develop out of axons that fail to cross to the other hemisphere. A team under neuroscientist Jerry Silver of Case Western Reserve University found evidence that these bundles might have conduction properties similar to those of intact nerve cells.

A more recent hypothesis comes from Tyszka and his colleagues. They derived insight from songbirds, whose acallosal brains also have synchronized hemispheres. A neural pathway based in the thalamus, near the center of the brain, relays information throughout the songbirds' cortex. The researchers hypothesize that the two halves of the human brain may also synchronize through the thalamus or through another midbrain structure.

Discovering how brains reorganize and resynchronize may lead to therapies for many different kinds of brain repair. Scientists have observed, for example, that individuals with autism and schizophrenia may have a smaller corpus callosum. This finding is in line with theories that these disorders involve low or aberrant connectivity in the brain.

Easing the challenges of people with a malformed corpus callosum is the immediate goal, however. Mellnik has come to accept the time it takes her to learn. When she graduated from high school, she swore she was done taking classes, but now she is a part-time college student. Mellnik sounds confident of her success. “I'm doing it at Sarah's pace,” she says and is not shy about adding: “I just made the dean's list.”