A Mysterious Connectivity Between Disconnected Brain Halves

Like a bridge that spans a river to connect two major metropolises, the corpus callosum is the main conduit for information flowing between the left and right hemispheres of our brains. Now, neuroscientists at the California Institute of Technology (Caltech) have found that people who are born without that link—a condition called agenesis of the corpus callosum, or AgCC—still show remarkably normal communication across the gap between the two halves of their brains. _MedXpress

Mysterious Connectivity Unexplained
The functional MRI images above reveal something entirely unexpected by brain scientists. Two different brains -- one with a normal corpus callosum connecting the two halves of the brain, and one without a corpus callosum -- appear to be functioning in the same, symmetrical, synchronous manner. How does this happen, without the normal super-highway of nerve connections between left and right cortex?

many areas of the brain display slowly varying patterns of activity that are similar to one another. The fact that these areas are synchronized has led many scientists to presume that they are all part of an interconnected network called a resting-state network. Much to their surprise, Tyszka and his team found that these resting-state networks look essentially normal in people with AgCC, despite the lack of connectivity.

“This was a real surprise," says Tyszka. "We expected to see a lot less coupling between the left and right brain in this group—after all, they are missing about 200 million connections that would normally be there. How do they manage to have normal communication between the left and right sides of the brain without the corpus callosum?”

The work used functional magnetic resonance imaging (fMRI) to demonstrate that synchronized activity between the left and right brain survives even this sort of radical rewiring of the nerve connections between the two hemispheres. The presence of symmetric patterns of activity in individuals born without a corpus callosum highlights the brain’s remarkable plasticity and ability to compensate, says coauthor Lynn Paul, research staff member and lecturer in psychology at Caltech. “It develops these fundamental networks even when the left and right hemispheres are structurally disconnected.”

The study that found the robust networks is part of an ongoing research program led by Paul, who has been studying AgCC for several decades. AgCC occurs in approximately one of every 4000 live births. The typical corpus callosum comprises almost 200 million axons—the connections between brain cells—and is the largest fiber bundle in the human brain. In AgCC, those fibers fail to cross the gap between the hemispheres during fetal development, forcing the two halves of the brain to communicate using more indirect and currently unknown means. _PO.MedXpress

The fine blog, GNXP, recently looked at agenesis of the corpus callosum in relation to autism and schizophrenia. The specific developmental events that occur in persons who are genetically susceptible to this malformation can be enormously instructive for the entire "nature vs. nurture" debate.

...formation of the corpus callosum is a dramatic example of a process that is susceptible to developmental variation. What I mean is this: when patients inherit a mutation that results in callosal agenesis, this phenotype occurs in some patients but not all. This is true even in genetically identical people, like monozygotic twins or triplets (or in lines of genetically identical mice). Though the corpus callosum contains millions of nerve fibres, the initial events that establish it involve very small numbers of cells. These cells, which are located at the medial edge of each cerebral hemisphere, must contact each other to enable the fusion of the two hemispheres, forming a tiny bridge through which the first callosal fibres can cross. Once these are across, the rest seem able to follow easily. Because this event involves very few cells at a specific time in development, it is susceptible to random “noise” – fluctuations in the precise amounts of various proteins in the cells, for example. These are not caused by external forces – the noise is inherent in the system. The result is that, in some people carrying such a mutation the corpus callosum will not form at all, while in others it forms apparently completely normally (see figure of triplets, one on left with normal corpus callosum, the other two with it absent). So, an all-or-none effect can arise, without any external factors involved.

This same kind of intrinsic developmental variation may also explain or at least contribute to the variability in phenotypic outcome at the level of psychiatric symptoms when these kinds of neurodevelopmental mutations are inherited. Even monozygotic twins are often discordant for psychiatric diagnoses (concordance for schizophrenia is about 50%, for example). This is often assumed to be due to non-genetic and therefore “environmental” or experiential factors. If these disorders really arise from differences in brain wiring, which we know are susceptible to developmental variation, then differences in the eventual phenotype could actually be completely intrinsic and innate. _GNXP

Fascinating indeed.

Now, back to the original mystery of how the two halves of the brain can coordinate and synchronise their activity without the main route of high speed connections between the hemispheres. Obviously in corpus callosum agenesis (AgCC), some nerve fibres do cross the midline. But for high fidelity synchrony to occur, one would probably expect the presence of high bandwidth connectivity, which is clearly not present in AgCC. To solve this mystery, we will need to functionally image such brains under a wide range of inputs. Stay tuned for the results of such studies.

The association of autism and schizophrenia with AgCC suggests that the ability of the brain to compensate for the loss of connections may not always be perfect. Again, much more information is needed.

Al Fin cognitivists understand that besides the anterior commissure and posterior commussure, there are other pathways between the hemispheres which could serve to accomodate a limited form of synchrony. But at what point does the synchrony begin to break down? It will be interesting to find out.