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Bridge between hemispheres

Alternative pathways connect distant areas on opposite sides of the brain

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A mystery of neuroscience that had remained unexplained for nearly half a century may have recently been solved by a group of researchers from Brazil and England. In principle, people born without an important brain structure called the corpus callosum should have difficulty associating learning and memory, which are stored in opposite hemispheres of the brain. The corpus callosum is a bundle of nerve fibers that connect the two sides. But surprisingly, in a paradox widely known to neuroscientists but never properly explained, some of these people’s brains appear to retain that ability. In an article published in the Proceedings of the National Academy of Sciences (PNAS) in May 2014, researchers provide a possible explanation for this decades-old conundrum. They found that the brains of people born without the corpus callosum seem to be able to create alternative routes and thus ensure communication between the brain’s two hemispheres. In the study, coordinated by physicians Fernanda Tovar-Moll and Roberto Lent, both from the D’Or Institute for Research and Education (IDOr) and the Biomedical Sciences Institute at the Federal University of Rio de Janeiro (UFRJ), the research group identified and morphologically described these new pathways, which appear to compensate for the absence of this important brain structure.

Situated in the center of the brain, the corpus callosum serves as a bridge that connects the right and left hemispheres with 200 million nerve fibers. Back in the 1960s, researchers observed that surgically removing the corpus callosum — a process known as callosotomy — diminished people’s ability to perceive and interpret the world. They saw that communication between the two hemispheres was severely compromised in people in which this structure had been surgically excised as a treatment for neurological disorders such as epilepsy. Because it is considered a palliative procedure and not a curative one, not to mention its extreme aggressiveness and invasiveness, callosotomy was and still is used only in very specific cases. “It was believed that in patients with epilepsy, callosotomy would prevent the malfunctioning neural connections that trigger the convulsions from spreading to neurons in the other hemisphere,” Tovar-Moll explains.

During surgery, the bundle of nerve fibers may be completely removed. The procedure interrupts the exchange of information between the brain’s two hemispheres, triggering what is known as interhemispheric disconnection syndrome. A blindfolded man whose corpus callosum has been completely excised may find himself unable to say the name of an object held in his left hand. This happens because left-hand tactile recognition is processed by the right hemisphere of the brain, whereas speech is controlled by the left hemisphere. For the man to both perceive the object and say its name, the two hemispheres must exchange information. Tovar-Moll explains that this inability is due to the absence of the bridge that allows signals to be transmitted from the right side of the brain to the left.

But scientists have also known for some time that people born without the corpus callosum do not have the same problem. In 1968, neuroscientist Roger Sperry, who won the Nobel Prize in Physiology or Medicine in 1981, saw that people born without the corpus callosum are able to recognize and speak the name of any object, regardless of the hand in which they hold it. Neuroscientists were intrigued by those findings — also known as Sperry’s paradox— since nobody knew for sure how one hemisphere was communicating with the other in the absence of the nerve bundle.

In their study published in PNAS, Tovar-Moll and her collaborators examined six people of both sexes, ages six to 33, and with varying degrees of malformation of the corpus callosum, ranging from its complete absence (agenesis) to underdevelopment. Among the volunteers who participated in the study, two had no corpus callosum; two had one smaller than normal (hypoplasia); and two had developed only parts of the structure (partial dysgenesis). By testing their tactile and visual recognition abilities, the researchers found that interhemispheric communication in people born without the corpus callosum or with only part of it was practically identical to that of a control group of people who had healthy brains.

In an attempt to better understand how the brains were working similarly in both groups, the researchers mapped out the subjects’ brains using structural magnetic resonance imaging (sMRI), which enabled them to visualize their neural connections, and functional magnetic resonance imaging (fMRI), which measures brain activity according to blood flow variations in different regions of the brain. The group observed that, differently from the brains of healthy people and of patients who had had the structure surgically removed, the brains of people with an absent or malformed corpus callosum presented alternative neural pathways connecting the two hemispheres, possibly present at birth. “In people born without the corpus callosum or who have a partially formed one, we identified a group of nerve fibers that form compact bundles, which connect the regions responsible for transferring tactile information between the two hemispheres,” says Tovar-Moll. There appear to be two alternative communication pathways between the brain’s hemispheres. According to her, these pathways create bilateral connections in the posterior parietal cortex region of the brain, the area associated with tactile recognition.

The group believes that in the case of people born without the corpus callosum, these alternative brain circuits are generated during embryonic development — between the 12th and 20th week of gestation —, when the anatomical plasticity of the brain is high and can reroute the growth of axons, the part of the neuron responsible for conducting electrical impulses from one cell to the other. Neuroscientists refer to this ability of the brain to reconnect distant areas as long-distance plasticity. The researchers don’t yet know whether everyone who is born without the corpus callosum develops these alternative neural routes. But the fact that this is being observed in some cases is certainly an indicator that this is possible. For now, the results obtained by Tovar-Moll and Lent’s group not only shed light on this longstanding paradox, but also suggest that even the long connections formed in the brain during its development can be modified, probably in response to environmental or genetic factors, opening the way for a better understanding of a series of human diseases that result from anomalous neural connections formed during in utero development.

Scientific article
TOVAR-MOLL, F. et al. Structural and functional brain rewiring clarifies preserved inter-hemispheric transfer in humans born without the corpus callosum. PNAS. May 2014.