Understanding the brain using topology: the Blue Brain project

ALERT ALERT! Applied topology has taken the world has by storm once more. This time techniques from algebraic topology are being applied to model networks of neurons in the brain, in particular with respect to the brain processing information when exposed to a stimulus. Ran Levi, one of the ‘co-senior authors’ of the recent paper published in Frontiers in Computational Neuroscience is based in Aberdeen and he was kind enough to let me show off their pictures in this post. The paper can be found here.

So what are they studying?

When a brain is exposed to a stimulus, neurons fire seemingly at random. We can detect this firing and create a ‘movie’ to study. The firing rate increases towards peak activity, after which it rapidly decreases. In the case of chemical synapses, synaptic communication flows from one neuron to another and you can view this information by drawing a picture with neurons as dots and possible flows between neurons as lines, as shown below. In this image more recent flows show up as brighter.

Image credit: Blue Brain project. This image shows a depiction of neurons and synaptic connections between them. The more recently a synaptic communication has been fired, the brighter it is depicted in the image.

Numerous studies have been conducted to better understand the pattern of this build up and rapid decrease in neuron spikes and this study contains significant new findings as to how neural networks are built up and decay throughout the process, both at a local and global scale. This new approach could provide substantial insights into how the brain processes and transfers information. The brain is one of the main mysteries of medical science so this is huge! For me the most exciting part of this is that the researchers build their theory through the lens of Algebraic Topology and I will try to explain the main players in their game here.

Topological players: cliques and cavities

The study used a digitally constructed model of a rats brain, which reproduced neuron activity from experiments in which the rats were exposed to stimuli. From this model ‘movies’ of neural activity could be extracted and analysed. The study then compared their findings to real data and found that the same phenomenon occurred.

Neural networks have been previously studied using graphs, in which the neurons are represented by vertices and possible synaptic connections between neurons by edges. This throws away quite a lot of information since during chemical synapses the synaptic communication flows, over a miniscule time period, from one neuron to another. The study takes this into account and uses directed graphs, in which an edge has a direction emulating the synaptic flow. This is the structural graph of the network that they study. They also study functional graphs, which are subgraphs of the structural graph. These contain only the connections that fire within a certain ‘time bin’. You can think of these as synaptic connections that occur in a ‘scene’ of the whole ‘movie’. There is one graph for each scene and this research studies how these graphs change throughout the movie.

The main structural objects discovered and consequentially studied in these movies are subgraphs called directed cliques. These are graphs for which every vertex is connected to every other vertex. There is a source neuron from which all edges are directed away, and a sink neuron for which all edges are directed towards. In this sense the flow of information has a natural direction. Directed cliques consisting of n neurons are called simplices of dimension (n-1). Certain sub-simplices of a directed clique for their own directed cliques, when the vertices in the sub-simplices contain their own source and sink neuron, called sub-cliques. Below are some examples of the directed clique simplices.

Image credit: EPFL. This image shows examples of directed cliques.

And the images below show these simplices occurring naturally in the neural network.

Image credit: Frontiers in Computational Neuroscience, ‘Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function’, Figure 1A. This image shows a reconstructed microcircuit produced using the model of neural activity. A 5-neuron clique is shown in red.
Image credit: Frontiers in Computational Neuroscience, ‘Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function’, Figure 1B3. This image shows a zoomed in depiction of the 5 neuron clique in the image above, with its corresponding simplex on the right.
 

Image credit: Frontiers in Computational Neuroscience, ‘Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function’, Adaptation of Figure 2C. This image shows a 6-simplex (a directed clique with 7 vertices) on the left and a 7-simplex on the right, with representations of how these cliques appear in the neural network shown in the centre.

The researchers found that over time, simplices of higher and higher dimension were born in abundance, as synaptic communication increased and information flowed between neurons. Then suddenly all cliques vanished, the brain had finished processing the new information. This relates the neural activity to an underlying structure which we can now study in more detail. It is a very local structure, simplices of up to 7 dimensions were detected, a clique of 8 neurons in a microcircuit containing tens of thousands. It was the pure abundance of this local structure that made it significant, where in this setting local means concerning a small number of vertices in the structural graph.

As well as considering this local structure, the researchers also identified a global structure in the form of cavities. Cavities are formed when cliques share neurons, but not enough neurons to form a larger clique. An example of this sharing is shown below, though please note that this is not yet an example of a cavity. When many cliques together bound a hollow space, this forms a cavity. Cavities represent homology classes, and you can read my post on introducing homology here. An example of a 2 dimensional cavity is also shown below.

An example of simplices sharing neurons.
Image credit: Frontiers in Computational Neuroscience, ‘Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function’, Figure 5A. This image shows an example of a two dimensional cavity. It is bounded by 2 simplicies (triangles) which are directed cliques with 3 neurons.
 

The graph below shows the formation of cavities over time. The x-axis corresponds to the first Betti number, which gives an indication of the number of 1 dimensional cavities, and the y-axis similarly gives an indication of the number of 3 dimensional cavities, via the third Betti number. The spiral is drawn out over time as indicated by the text specifying milliseconds on the curve. We see that at the beginning there is an increase in the first Betti number, before an increase in the third alongside a decrease in the first, and finally a sharp decrease to no cavities at all. Considering the neural movie, we view this as an initial appearance of many 1 dimensional simplices, creating 1 dimensional cavities. Over time, the number of 2 and 3 dimensional simplices increases, by filling in extra connections between 1 dimensional simplices, so the lower dimensional cavities are replaced with higher dimensional ones. When the number of higher dimensional cavities is maximal, the whole thing collapses. The brain has finished processing the information!

Image credit: Frontiers in Computational Neuroscience, ‘Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function’, Figure 6B

The time dependent formation of the cliques and cavities in this model was interpreted to try and measure both local information flow, influenced by the cliques, and global flow across the whole network, influenced by cavities.

So why is topology important?

These topological players provide a strong mathematical framework for measuring the activity of a neural network, and the process a brain undergoes when exposed to stimuli. The framework works without parameters (for example there is no measurement of distance between neurons in the model) and one can study the local structure by considering cliques, or how they bind together to form a global structure with cavities. By continuing to study the topological properties of these emerging and disappearing structures alongside neuroscientists we could come closer to understanding our own brains! I will leave you with a beautiful artistic impression of what is happening.

Image credit: Blue Brain project. This image shows an artists depiction of their interpretation of the results, projected into 3 dimensions. The simplices are represented by the clique-like small structures and the centre is the artists depiction of a cavity.

There is a great video of Kathryn Hess (EPFL) speaking about the project, watch it here.

For those of you who want to read more, check out the following blog and news articles (I’m sure there will be more to come and I will try to update the list)

Frontiers blog

Wired article

Newsweek article