The brain adapts, through reorganization, in people born without a corpus callosum who lack a bridge between the two cerebral hemispheres. It is thought that these mechanisms enable the brain to compensate for the losses by recreating connections to other brain regions using alternative neural pathways.

When the neuronal fibers that act as a bridge between the hemispheres are missing, the brain’s reorganization creates an impressive number of connections inside each hemisphere. A new study shows that this reorganization creates more intra-hemispheric connections than in a healthy brain, indicating that plasticity mechanisms are involved. It is thought that these mechanisms enable the brain to compensate for the losses by recreating connections to other brain regions using alternative neural pathways.

This work is published in Cerebral Cortex in the paper, “Structural Neuroplastic Responses Preserve Functional Connectivity and Neurobehavioral Outcomes in Children Born Without Corpus Callosum.”

One in 4,000 people is born without a corpus callosum—a brain structure that transfers information from one hemisphere to the other. The corpus callosum, which develops in utero between the tenth and twentieth week of gestation, is the largest white matter pathway in the brain connecting the two hemispheres.

When the corpus callosum is missing, nothing replaces the structure with the exception of cerebrospinal fluid. This means that the information transmitted from one hemisphere to the other can no longer be conveyed by the neuronal projections from the corpus callosum.

Surprisingly, 25% of people with this malformation have no visible signs, 50% have average intelligence quotients and learning difficulties, and the remaining 25% suffer from severe cognitive disorders.

“Their role in a healthy brain,” said Vanessa Siffredi, PhD, a researcher in UNIGE’s Faculty of Medicine, “is to ensure the functioning of various cognitive and sensorimotor functions.”

In the absence of the corpus callosum, certain fibers designed to serve as a bridge between the hemispheres, known as Probst bundles, bypass the absent brain area and curl up inside each hemisphere. “The back-up zones vary from one individual to another. And we don’t understand their functions,” explained Siffredi.

The UNIGE scientists—working in collaboration with their colleagues at the University of Melbourne—set out to understand this variability and to examine the role of the fibers. Their hypothesis was that developmental absence (agenesis) of the corpus callosum may lead to the neuroplastic response of strengthening of intrahemispheric pathways.

Using MRI brain imaging, they studied the anatomical and functional links between different brain regions of approximately 20 Australian children aged 8 to 17 suffering from agenesis of the corpus callosum compared with typically developing controls (n=29).

This approach made it possible to observe the physical relationships between the different regions of the brain, i.e., their structural links. In children with corpus callosum agenesis, the neural fibers inside each hemisphere are greater in number and of higher quality than in healthy brains. Furthermore, the UNIGE scientists succeeded in determining the correlations between the activity of different brain regions and their functional links.

“If two regions are active together, it means they are communicating with each other,” explained Siffredi. The data show that intra- and inter-hemispheric functional connectivity of brains without the corpus callosum are comparable to those of healthy brains. “Remarkably, communication between the two hemispheres is maintained. We think that plasticity mechanisms, such as the strengthening of structural bonds within each hemisphere, compensated for the lack of neuronal fibers between hemispheres. New connections are created and the signals can be re-routed so that communication is preserved between the two hemispheres.”

The team not only observed structural strengthening of intrahemispheric pathways in children born without a corpus callosum, but also observed a correlation between the increase in intra-hemispheric connections and cognitive skills.

This information is relevant for clinical work since, as agenesis is currently detected by means of ultrasound during pregnancy, it can be met with the proposal to terminate the pregnancy.  “In the not-too-distant future, we could imagine using MRI imaging to predict whether the malformation observed by ultrasound runs the risk of being associated with cognitive impairment or not, and so better inform future parents,” concluded Siffredi.

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