Uncovering new ways to understand the inner workings of the brain: the weather and the markovian brain. **First Post**

Hello! My name is Dan Akarca - I'm completely new to this platform and hope you'll enjoy reading my posts... This will be an area for me to write about advances in brain sciences, philosophy and generally interesting things (at least to myself). I'm a graduate in Neuroscience from Cambridge University and I'm currently a Medical Student - I hope you'll enjoy!

This first post is about some work I carried out as Master's student developing methods to capture how the brain functions.

The brain is an incredibly complex dynamic system. It can be very difficult to understand how specific differences within that system can be associated with the cognitive and behavioural difficulties that some people experience. This is because even if we group people together on the basis that they all have a particular l disorder, that group will likely have a heterogeneous aetiology. That is, even though they all fall into the same category, there may be a wide variety of different underlying brain causes. This makes these disorders notoriously difficult to study.

Developmental disorders that have a known genetic cause can be very useful for understanding these brain-cognition relationships, because by definition they all have the same causal mechanism (i.e. the same gene is responsible for the difficulties that each child experiences). I've been studying a language disorder (at Cambridge University) caused by a mutation to a gene called ZDHHC9. These children have broader cognitive difficulties, and more specific difficulties with speech production, alongside a form of childhood epilepsy called rolandic epilepsy.

In our lab, we have explored how brain structure is organised differently in individuals with this mutation, relative to typically developing controls. Since then our attention has turned to applying new analysis methods to explore differences in dynamic brain function. We have done this by directly recording magnetic fields generated by the activity of neurons, through a device known as a magnetoencephalography (MEG) scanner. The scanner uses magnetic fields generated by the brain to infer electrical activity.

The typical way that MEG data is interpreted, is by comparing how electrical activity within the brain changes in response to a stimulus. These changes can take many forms, including how well synchronised different brain areas are, or the how size of the magnetic response differs across individuals. However, in our current work, we are trying to explore how the brain configures itself within different networks, in a dynamic fashion. This is especially interesting to us, because we think that the ZDHHC9 gene has an impact on the excitability of neurons in particular parts of the brain, specifically in those areas that are associated with language. These changes in network dynamics might be linked to the kinds of cognitive difficulties that these individuals have.

We used an analysis method called “Group Level Exploratory Analysis of Networks” – or GLEAN for short – and has recently been developed at the Oxford centre for Human Brain Activity. The concept behind GLEAN is that the brain changes between different patterns of activation in a fashion that is probabilistic. This is much like the concept of the weather – just as the weather can change from day to day in some probabilistic way, so too may the brain change in its activation.

This analysis method not only allows us to observe what regions of the brain are active when the participants are in the MEG scanner. It also allows us to see the probabilistic way in which they can change between each other. For example, just as it is more likely to transition from rain one day to cloudiness the next day, relative to say rain to blistering sun, we find that brain activation patterns can be described in a very similar way over sub-second timescales. We can characterise those dynamic transitions in lots of different ways, such as how long you stay in a specific brain state or how long does it take to return to a state once you’ve transitioned away. We have found that a number networks differ between individuals with the mutation and our control subjects.

(This is one of the brain states showing the most difference in brain activation pattern).

Interestingly, these networks strongly overlap with areas of the brain that are known to express the gene (we found this out by using data from the Allen Atlas). This is the first time that we know of that researchers have been able to link a particular gene, to differences dynamic electrical brain networks, to a particular pattern of cognitive difficulties.

Thanks for reading my first post!

DA