Summary: Myelin is more complex and dynamic than previously believed.
Source: University of Oxford
Alberto Lazari of the Nuffield Department of Clinical Neurosciences explains the importance of insulation in our brains’ wiring.
Our brains contain a striking amount of ‘brain wires’, which allow electrical signals to send important information from one corner of the brain to another.
Although these brain wires are made up of biological material, they also bear surprising resemblances to the electrical wires you can see when you do a DIY job in your home. For instance, one key feature that allows the brain wires to work is that they are tightly insulated.
A little bit like metal wires are coated with plastic, brain wires are also wrapped in an insulation material, called ‘myelin’. Myelin is essentially a fatty layer of insulation, wrapped around many of the wires in your brain.
Myelin is incredibly important. When this insulation layer breaks down, the brain struggles to transmit signals at its usual speed, which is what happens in conditions like multiple sclerosis. However, the insulation of brain wiring has often been overlooked by scientists. It is particularly difficult to measure non-invasively in a live human.
On top of that, this insulation has long been considered a static part of the brain which is not particularly relevant to understanding the brains of healthy adults.
While myelin is clearly important in multiple sclerosis, until recently very few scientists had studied myelin beyond the realm of disease.
However, recent studies have now called some assumptions about myelin into question. In particular, in the past decade many labs around the world, including here at Oxford, have shown that myelin is more complex and dynamic than previously thought.
Ground-breaking new methods have also been developed to effectively measure fat-rich insulation through magnetic resonance imaging (MRI), allowing us to ask new questions about this ever-elusive insulation layer that envelops our brain wiring.
For example, we know that everyone has a different brain, and brain wiring is one way that our brains differ from each other. Do different people have different levels of wiring insulation? And do these differences between individuals influence how our brains work? As simple as these questions may sound, they had not been asked before – until now.
At the Wellcome Centre for Integrative Neuroimaging, we set off to find an answer, using new MRI techniques to study myelin.
First, we scanned a large group of participants and captured detailed MRI brain scans which gave us information about myelin. We then tested the same participants with a type of non-invasive brain stimulation called Transcranial Magnetic Stimulation, or TMS. Using TMS, we can create fast electrical signals and track them across the brain on a millisecond scale.
This technique allowed us to capture fast electrical communications between brain areas – even those on opposite sides of the brain.
This was particularly useful, because this very rapid electrical communication along brain wires is exactly what we expect would be influenced by insulation, very much in the way that the insulation of metal wires in our homes changes their electrical conductance.
Our findings showed for the first time that variation in brain wiring insulation between people is associated with significant differences in how brain areas communicate. For example, participants with more myelin in a given “brain wire” connecting two brain regions also tend to have a stronger electrical connection between those two brain regions.
This is important because it confirms the significance of myelin not just to disease, but also to the everyday functioning of the brain. It also demonstrates the utility of studying myelin to understand the fine details of how different regions of the human brain communicate with each other.
Finally, our results also carry important practical implications. If our individual brain wiring insulation is linked with how we respond to brain stimulation, could information about myelin be used in the future to study clinical responses to brain stimulation?
For example, TMS is already being used as a promising therapy for major depression, but with huge variability in how people respond to this treatment.
Could information about brain wiring insulation tell us more about why some people respond better than others to TMS? And could this eventually help us better tailor treatment? We still do not have answers to these questions.
However, what is certain is that this fat-rich insulation of our brain wiring, once thought to be a totally uninteresting part of the brain, is likely to have some more exciting surprises in store for us.
A macroscopic link between interhemispheric tract myelination and cortico-cortical interactions during action reprogramming
Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts.
Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them.
As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects.
We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics.
These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.