Connectomics: The Future of Neuroscience
In the past, humanity has been able to engineer itself to the moon, eradicate fatal diseases, and build a massive global communications network, but for a species that has managed all of these worldly feats, we know surprisingly so little about one area in particular; ourselves!
The root of each thought we have and every action we take is in the brain, which also holds intimate records of all of our emotions, personal experiences, and memories. Essentially, it’s the key to understanding what makes us human.
Although currently there is a huge gap in how much we actually know about this magnificent organ, the emergence of connectomics is bringing us closer and closer to answering questions fundamental to the field of neuroscience. But before we dive into that, let’s go back to the basics!
Neural Connectivity
A neuron is a type of nerve cell which communicates information between the brain and the nervous system through both chemical and electrical signals. Argued to be the most complex biological mechanism in the entire universe, your brain is made up of nearly 100 billion neurons. To put it into perspective, that’s roughly the number of stars in the Milky Way.
The neuron is composed of 3 main parts:
1. Cell Body (Soma) — where the DNA and nucleus are located
2. The Dendrites — branch-like structures whose membranes contain receptor molecules
3. Axon — the long, thin “cable” which carries electrical impulses known as action potentials away from the cell body and towards the axon terminal
You can consider the branches (the dendrites) of the neuron to be like strands of spaghetti: each strand touches many other strands on a plate just like how one neuron’s branches contact many other neurons.
When the dendrite of one neuron is able to transmit a message to the axon terminal of another neuron, their point of communication is known as a synapse. These synapses allow for the formation of over 700 trillion neural connections within our brain !!
The neural connections in our brains form extensive interconnected networks. Synaptic connections can also strengthen, weaken, or be eliminated altogether in a phenomenon known as neural plasticity, which allows for the organization of these connections to be rewired.
So clearly the neural circuitry in our brain is insanely complex and ever-changing. How would we even begin to understand the vastness that is our brain if it has an incomprehensible number of wires and cells? Well, let me introduce you to my dear friend…
The Connectome!
Just like how your genome is the complete sequence of your genetic information, your connectome is the complete diagram of the connections between the neurons in your brain. Connectomics is the study of these connectomes and encompasses the most effective ways to map your brain. The name of this field emphasizes how at the core, the most important aspect of our brains are the connections found within them.
Currently, the only organism that neuroscientists have a complete connectome of is a roundworm known as the C. Elegan, with a map that has a total of only 302 neurons. This is a mere speck in comparison to the human brain’s extensive connectivity which is eleven orders of magnitude more complex than the C. Elegan’s.
As mentioned before, the insane complexity of our brains has made being able to deepen our understanding of neuroscience incredibly challenging, and brain imaging techniques used today don’t allow for a micro-scale view of individual neurons or neural wirings. This means that the current brain imaging methods provide us with virtually zero physical indicators for many diseases and they just don’t give us enough information on the brain in order to effectively diagnose conditions such as Alzheimer’s.
You can compare this to if your doctor told you that you had a hairline fracture in one of your bones purely on the basis of how much pain you felt in a particular area, without actually knowing what was exactly happening inside your body. You’d probably call your doctor crazy for having absolutely no logic and demand to have an x-ray!
The good news is that new methods in brain imaging are advancing the field of connectomics. Initiatives that aim to build a complete human connectome such as the Human Connectome Project (HCP) have allowed for the emergence of more advanced imaging methods for both functional and structural connectivity.
What is the Difference Between Structural and Functional Connectivity?
Structural connectivity focuses on the large-scale wiring of the brain and on neural pathways that have been established over longer periods of time.
Examples of this include:
- sMRI
- Diffusion-Weighted Imaging ( DWI )
- Diffusion Tensor Imaging ( DTI )
- Diffusion Spectrum Imaging ( DSI )
Meanwhile, functional connectivity focuses on gathering data on live neural activity and how different regions of the brain work together. To date, this is where the majority of brain imaging work has been done.
Examples of these techniques are:
- fMRI
- EEG
- ECoG
- MEG
- PET Scans
Advancements in Connectomics
Below is a breakdown of a few of the latest developments of brain imaging techniques in connectomics!
Brainbow Technique
The Brainbow is a technique where each individual neuron is inserted with multicolored fluorescent proteins resulting in a randomized gene expression that causes every neuron to glow with up to 100 different hues! This method can also be used with viruses such as rabies that infect the human brain through the process of modifying the virus to leave a trail of the colored fluorescent protein as it travels through the neural connections of the brain.
Although this technique allows for the visibility of neural circuits in certain areas, in regions such as the cerebral cortex, you can’t tell the colors apart because the cerebral cortex is just waaay too densely packed with wires and cells.
Luckily, the same neuroscientists that drove this innovative genetic engineering technique, managed yet another impressive feat… just more on the mechanical side of things this time.
Automatic Tape-Collecting Lathe Ultramicrotome (ATLUM)
The team at Lichtman Labs at Harvard University that made a breakthrough with Brainbows, developed a device that automates the extremely thin sectioning and scanning of cubic millimeters of brain tissue called the Automatic Tape Collecting Lathe Ultramicrotome or ATLUM for short.
Yikes… try saying that 10 times fast… yeah I think the acronym should suffice.
Unlike Brainbows which used light microscopes and depended on wavelengths to see neurons, ATLUM depends on electron microscopy to be able to view neurons at a much higher resolution.
Here’s the breakdown of how this awesome machine works :
Electron microscopes don’t penetrate very deep into the tissue, so sections of brain tissue have to be cut into extremely thin slices at a thickness of only 300 atoms in order to produce highly detailed maps of neurons. These slices are filled with a metal called osmium and are encased in plastic before being cut against a fine diamond point.
Since the slices are so flimsy, they are floated on water and then picked up by a conveyer belt in an assembly line fashion.
These sections create a “film strip-like tape” of the brain tissue which is then cut and pasted onto silicon wafers.
The tape is then scanned under the electron microscope to create digital images of each and every section of brain. When 33,333 of these images are stacked, they form one cubic millimeter of a digital, 3D cube of the brain. In order to be able to identify each neuron, each cell is filled with various colors in a process called segmentation.
Segmentation helps in digitally reconstructing neural circuitry, but even this reconstruction is an insanely small section of the brain !! It can take thousands upon thousands of scans to see neural connections from end to end.
The image above is of reconstructed cells in the cortex, but that image is actually quite sparse in comparison to the extremely minute area of the brain found within the reconstructed cells, (shown in the image below) which projects what a 100% fully mapped section of the brain looks like.
Sadly, this amorphous area of brain contains only about 700 synapses, 600 axons, and 90 dendrites. BUT you gotta start somewhere right?
How Artificial Intelligence is Impacting Connectomics
These processes can seem rudimentary and excessively tedious, but thankfully advances in Artificial Intelligence are enabling for faster developments in the field of connectomics. For example, AI systems developed by neuroscientist Sebastian Seung are currently being used to analyze images of brain slices produced by Lichtman’s Lab.
Initially, neuroscientists had to manually color in each cell of a digital brain slice, but now Convolutional Neural Networks (CNNs) and computer vision are also able to autonomously color in the neural pathways in the brain scans. Considering that a model of a full human connectome will be more data than all of the digital content that currently exists in the entire world, AI will be crucial for a more rapid progression in the sector of connectomics.
BONUS: If you want to see some connectomics and AI in action, check out this cool game that allows the user to help reconstruct 3D neurons and aid in mapping the brain! No scientific background necessary, just some curiosity!
Future of Connectomics
Although the future for connectomics can seem excruciatingly slow-paced if you take into account that building a mouse connectome by the year 2030 is considered on the ambitious side, the immensely beneficial progressions in neuroscience that connectomics would lead to are undeniable. Further developments in connectomics would enable:
- Proper investigation into the link between brain mechanisms and psychological behaviors
- The collection of hyper-specific information on how diseases in the brain look as well as physical biomarkers of neurological conditions
- More personalized treatments in neurology
- The potential to obtain a greater understanding of how memories are encoded in our neural wiring and the possibility of one day being able to retrieve memories engrained in our brain’s circuitry (totally a topic that deserves its own dedicated discussion)
Connectomics opens up an exciting new frontier for the world of neuroscience and I’m 100% here for it. Maybe there’ll even be a downloaded version of my connectome in the rapidly evolving future, but that is an extremely fascinating idea for another article!
TL;DR
- Our brains are extremely complex and our current brain imaging methods are still behind in gathering a lot of the information that we need to further our understanding of the brain
- Connectomics is the field that aims to create a map of all the neuronal connections in your brain
- The Brainbow Technique uses fluorescent proteins to trace individual neurons
- Electron Microscopy allows for a much higher resolution of neurons over Light Microscopes
- The ATLUM created a more efficient way to image and analyze brain slices
- Coloring and identifying each neuron in the process of segmentation made creating digital reconstructions of neurons possible
- AI is helping advance connectomics through the use of computer vision that can independently color in neural pathways in the brain
- A full connectome means the possibility of one-day resurfacing memories and developing more personalized treatments in neurology.
End Note to the Reader: Hey I’m Sualeha, I’d love to hear your thoughts on this article, so definitely feel free to connect with me to start a conversation! Any feedback, that you the reader might have for improvements is 100% welcome! Thank you so much for taking the time to read my content!
- Email: sualeha.irshad@gmail.com
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