Connectomics: An Overview
Everything you need to know about the field of connectomics and its applications
Did you know that scientists can inject a fake memory into mice to make them think they were injured when they weren’t? Crazy, right?! 🤯But imagine if we could do that to humans! Unfortunately, to do this, we would need to actually understand how our brain works. And this is where connectomics comes in, finding the connections in the brain 2005.
A Brief History of Connectomics
I don’t know about you, but I feel like the best way to understand a topic is to first understand the history behind it. Technically speaking the field of connectomics first appeared in 2005, but we have been doing research on the brain since 1672!!
It all started with a man named Thomas Willis. Through his drawings, he proposed that higher cognitive functions came from the convolutions of the cerebral cortex. A convolution is a fold on the brain.
Then, in 1786, another man named Karl Friedrich Burdach first described the structure of the brain. This kickstarted the beginning of the study of the brain and how it works, and like a trend now quickly spread. People including; Marie Anttoniete’s personal physician and the director of the psychiatric clinic at the University of Vienna, and other well-known people took interest in trying to understand how we think.
Soon enough, in the early 1900s people began to realize that the brain was composed up of a circuit of neurons. Now the focus shifted from trying to understand the brain to try to understand the connections of the brain.
And now finally, we bring it back to the future, with the field of connectomics having many applications including; figuring out mental illnesses, mapping the connectome, and more! With many groups such as the Human Connectome Project working hard, the future is bright for this exciting field.
In order to understand how the brain connects and communicates, we need to understand the brain itself, right?! We know at this point that the brain is made up of circuits that allow it to communicate. But, what are these circuits made of?
The neuron is the star of our show here. It is what allows us to communicate in the brain. Basically, it is a specific type of cell that can be electrically excited to communicate with other cells. It makes up most of our nervous tissue]
There are 3 main parts of the neuron:
- The Cell Body
Let’s start with the cell body. The cell body, just like the human body, is the main core of its function. It carries its genetic information, gives it structure, and most importantly powers it!
Next is the dendrite. Dendrites are fibrous roots that reach out from the cell body. Think of it as a plant. The dendrites receive and process signals from the axons, just like an antenna to the radio. While the axon is the communicator, the dendrite is the recipient.
Finally, we have the axon. As mentioned before, the axon is like the communicator. It is a long, tail-like structure insulated in a fatty substance called Myelin. This substance allows for the axon to conduct an electrical signal and give it to the dendrite.
Together, the neuron makes up an important part of the brain, that allows for the neurons to communicate and connect.
What is Connectomics?
So, what even is connectomics? Connectomics, at least according to the dictionary, is the study of mapping the wiring of the brain. Basically, we’re looking at the way the brain communicates in a way similar to how a circuit in a computer might communicate.
Now in this circuit, we have specific sites where the neurons connect, called synapses. The human brain has over 160 million of them! The neurons send information to the synapse and then, the synapse sends this information to another target neuron. And this is how our brain communicates. Think of it like sending a letter in the mail, the post office receiving the letter and then giving it to the friend you sent it to.
Together, all of these synapses make up the connectome. The connectome is similar to the genome in this way, and the goal of connectomics is to map it.
Methods in Mapping the Connectome
How do we even do this? There are millions of synapses in the brain, and they are all pretty small, so how do we even look at them?
The Brainbow is actually very similar to how it sounds! Creating a rainbow in the synapses of the brain so we can observe them. The Brainbow is a way to genetically label the neurons through fluorescent proteins.
In order to create this “rainbow,” mice are genetically engineered to express fluorescent proteins. These fluorescent proteins then express different amounts of 3 colors; green, blue, yellow, and red, at random ratios using a gene-editing technique called; Cre recombinase-mediated DNA excision and DNA inversion.
The different colors expressed allow us to view hundreds of synapses at once, instead of only a few at a time. Basically, think of it like looking at the different colored wires in your computer to figure out how they connect. Plus, it creates a really awesome picture!
The Automatic Tape Collection Method
There’s a big issue in connectomics. In order to understand the brain, we need to look at its neural circuits, which are found in large volumes of tissue. But, the processes composing the circuits, the axons and dendrites, are extremely thin and interconnected. This makes it very hard to view both the circuit and the pieces that make up the circuit, which is why the automatic tape collection method was made.
The machine works by sectioning the block of brain tissue into really tiny pieces called, ultrathin sections. It collects these tiny sections of a long piece of tape coated in carbon, which we can later use to view the connections under a microscope. The great thing, it’s all completely automated!
High Throughput Electron Microscopy
In connectomics, we need to generate large amounts of data in order to gather the information we need. And even though we can store this data when we get it, getting it is another story. Which is where the high throughput electron microscope comes in.
The electron microscope is a microscope with a big camera on it that allows us to both view large areas and view connections in close details. This means that we can collect the large amount of data we need in an efficient amount of time. Think of it like using a camera to zoom in on an animal far away from you. The microscope allows us to do that!
Digesting the Information
So now that we have all of this data, how do we process it? How can we actually figure something out from the mess of colors and numbers?
AI and Connectomics
Part of the issue in digesting our data is that it can be hard for us to see if a spot is a synapse or just a blob. And this is where AI comes in. AI or Artificial Intelligence is excellent in data classification. Think of it like using a special magnifying glass that tells you the answer.
One of these algorithms was originally created in 2015. See the algorithm works by seeding itself into the pixels of the image we have generated and then uses a convolutional neural network to predict which neurons are part of the synapse and fills it in.
We can then use the data we have created to reconstruct a synapse, so we can view it.
Connection Matrices are how we can actually create a map of the connectome, just like a map of a road! This map is made up of smaller graphs, called brain networks.
Brain networks are made up of two parts; the nodes (neuronal elements) and edges (the interconnections). These networks help us measure the structure and function of the connections.
We can then use special statistical tools to read these graphs! This is separated into 2 main parts; segregation and integration.
Segregation is finding the extent to which the nodes accumulate in a certain area. Think of it like finding where the most middle-schoolers clump in the hallways. This allows us to measure the network’s clustering coefficient, which means its tendency to form different modules.
Integration measures the ability for communication along network paths. Think of it like tracing dropped calls in a certain area to find out which part needs higher coverage. This allows us to determine how nodes exchange information and how it relates to communication efficiency.
These tools allow us to understand how the brain works, especially when looking at mental illnesses.
Talking about understanding the networks in our brain brings us to the next point, the amazing totally cool applications of connectomics.
When you hear mental illness, you probably think of therapy and drugs, which is actually the problem. We have been failing to address the issue, which is the brain. And this is where connectomics can help. By using functional connectomics, looking at how to brain is functionally connected, we can start to understand how mental illness actually works.
One example of this is in Mikey Taylor’s awesome article where he describes how he used connectomics and AI to diagnosis Schizophrenia. He uses fMRI, functional MRI, data to break down the brain, and with machine learning finds the biomarkers for Schizophrenia. You can read the full article here.
Another example is Saeed Lab’s work with using connectomics to understand Autism. They use connectomics and machine learning to break down fMRI data in autism patients, in order to understand the connections that cause Autism. You can also find this article here.
Addiction is a very real problem in our society today, but fortunately, we have a tool that can help us understand and prevent it. With connectomics, we can identify biomarkers in the brain that are found in individuals with addiction or risk of addiction.
In the AJP, we hear about research using connectomics to detect cocaine addiction. They are using a machine learning algorithm to break down the brain and understand the connections that cause some people to become addicted, in order to predict addiction in individuals. You can find the article here.
Did you know that just like our fingers, our brains have their own, unique fingerprints?! Crazy, right? This called our brain fingerprint, and everyone has a completely unique one. Every experience we have changed our brain. And this fingerprint, made up of the connections in our brain, can actually be really helpful.
One way we can use this brain print is in the conviction of a criminal. It is pretty much impossible to change your brain, which means that it is a pretty reliable source of identification. Is it more invasive? Of course! But, there are minimally invasive ways to track this, such as EEG’s. You can learn more about this here.
There are so many other applications of connectomics! Some of these include understanding Parkinson's, doing speech-language assessments, and curing mood disorders! If you want to read more about these, I recommend this book.
Connectomics is an amazing field with limitless potential. Today, we looked at just the very tip of the iceberg of this field.
- Connectomics, a relatively new field, has actually been around for thousands of years
- The neuron has 3 parts; the cell body, the dendrite, and the axon that help communicate important information in our brain
- Connectomics is the field of studying the wiring and connections in the brain
- The BrainBow is a method to map the brain by genetically editing mice to express fluorescent proteins
- Automated Tape Method System allows for users to view the big view of the brain while also looking at the small intricate connections
- The High Throughput Electron Microscopy allows us to look at really tiny connections in the brain, while also looking at the big picture
- One way we can digest information in connectomics is using AI. It allows us to reconstruct synapses in the brain and better identify other synapses.
- Another way is by creating connection matrices, which let us look at the map of the connections in the brain
- Connectomics has many applications including; understanding, diagnosing, and treating Parkinson’s disease, mental illnesses, strokes, and even convicting criminals
If you’ve made it this far, thank you! I am a 15-year-old who is interested in regenerative medicine, biocomputing, and public health. If you want to see me continue to grow and 10X myself, sign up for my newsletter here!