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Developmental Biology - Brain Plasticity

Brain Malformation Reveals Incredible Brain Plasticity

People born without a corpus callosum manage to bridge between the two cerebral hemispheres of their brain...

One in 4,000 people is born without a corpus callosum. This part of our brain consists of neural fibres which transfer information from one brain hemisphere to another. A quarter of those born without a corpus callosum have no symptoms, while the remainder may either have low intelligence quotients or may suffer severe cognitive disorders.
The corpus callosum develops in utero between the tenth and twentieth week of gestation.

In a study published in the journal Cerebral Cortex, neuroscientists from the University of Geneva (UNIGE) discovered that when neuronal fibres bridging between hemispheres are missing, the brain reorganises itself — creating an impressive number of connections inside each affected hemisphere.

This reorganization creates more intra-hemispheric connections than found in a healthy brain, which indicates brain plasticity mechanisms are involved. It is thought that such mechanisms enable the brain to compensate for its losses by recreating connections to other brain regions using alternative neural pathways.
25% of people with this malformation have no visible signs; 50% have average intelligence quotients and learning difficulties. The remaining 25% suffer with severe cognitive disorders.

Mysterious Fibres

Agenesis, or missing, of the corpus callosum is a congenital brain malformation in which brain structure fails to develop — resulting in one out of 4,000 babies born without a corpus callosum. While missing, nothing can replace this structure measuring about ten centimetres, 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.

"Their [neuronal projections] role in a healthy brain is to ensure the functioning of various cognitive and sensory motor functions," explains Vanessa Siffredi, a researcher in UNIGE's Faculty of Medicine. The scientific literature shows that, in the absence of the corpus callosum, certain fibres known as Probst bundles, were designed to serve as a bridge between brain hemispheres, bypassing that absent brain area and curl up inside each hemisphere. "The back-up zones vary from one individual to another — and we don't yet understand their functions," explains Siffredi.

UNIGE scientists, working in collaboration with colleagues at the University of Melbourne, set out to understand this variability and examine the role of these fibres. Using MRI brain imaging, they studied anatomical and functional links between different brain regions in approximately 20 Australian children aged 8 to 17 suffering with agenesis of the corpus callosum.

A Salutary Role

This approach made it possible to observe physical relationships between the different regions of the brain, i.e. the structural links. In children with corpus callosum agenesis, neural fibres inside each hemisphere are greater in number and of higher quality than in healthy brains! Furthermore, UNIGE scientists succeeded in determining the correlations between activity in different brain regions as well as their functional links.
"If two regions are active together, it means they are communicating with each other."

Vanessa Siffredi PhD,Institute of Bioengineering, Center for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, Geneva, Switzerland; Department of Radiology and Medical Informatics, Faculty of Medicine, University of Geneva, Switzerland; Brain and Mind Research, Clinical Sciences, Murdoch Children’s Research Institute, Melbourne, Victoria, Australia; Division of Development and Growth, Department of Paediatrics, Faculty of Medicine, University of Geneva, Switzerland.

The data shows 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 fibres between hemispheres.

New connections are created and the signals can be re-routed so that communication is preserved between the two hemispheres."

Vanessa Siffredi PhD.

Predicting Cognitive Impairment

The Geneva neuroscientists likewise observed a correlation between the increase in intra-hemispheric connections and cognitive skills. This information is very interesting for clinical work since, as agenesis is currently detected by means of ultrasound during pregnancy, it is often proposed [prior to these findings] that a pregnancy be terminated.
"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."

Vanessa Siffredi PhD.

The corpus callosum is the largest white matter pathway in the brain connecting the two hemispheres. In the context of developmental absence (agenesis) of the corpus callosum (AgCC), a proposed candidate for neuroplastic response is strengthening of intrahemispheric pathways. To test this hypothesis, we assessed structural and functional connectivity in a uniquely large cohort of children with AgCC (n = 20) compared with typically developing controls (TDC, n = 29), and then examined associations with neurobehavioral outcomes using a multivariate data-driven approach (partial least squares correlation, PLSC). For structural connectivity, children with AgCC showed a significant increase in intrahemispheric connectivity in addition to a significant decrease in interhemispheric connectivity compared with TDC, in line with the aforementioned hypothesis. In contrast, for functional connectivity, children with AgCC and TDC showed a similar pattern of intrahemispheric and interhemispheric connectivity. In conclusion, we observed structural strengthening of intrahemispheric pathways in children born without corpus callosum, which seems to allow for functional connectivity comparable to a typically developing brain, and were relevant to explain neurobehavioral outcomes in this population. This neuroplasticity might be relevant to other disorders of axonal guidance, and developmental disorders in which corpus callosum alteration is observed.

Vanessa Siffredi, Maria G Preti, Valeria Kebets, Silvia Obertino, Richard J Leventer, Alissandra McIlroy, Amanda G Wood, Vicki Anderson, Megan M Spencer-Smith and Dimitri Van De Ville.

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Nov 11 2020   Fetal Timeline   Maternal Timeline   News

In healthy brain, two hemispheres are connected by the corpus callosum (RED) fibers.
Fibers are absent in brain with Corpus Callosum Agenesis. CREDIT Unige/Siffredi

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