The Connectome

By Raayan Dhar

A current problem faced by neuroscientists is mapping every neuron in an organism's brain. Previous technology used to map neurons—such as MRI, fMRI, CT, and PET scans—were deemed unsuccessful for multiple reasons. MRI (magnetic resonance imaging) uses magnetic and radio waves to produce images of the brain and brainstem. MRI scans give detailed pictures of soft tissue, ignoring hard bone and air. fMRI (functional magnetic resonance imaging) scans and detects changes in blood oxygen flow in response to neural activity. When an area of the brain is in use, blood flow to that region increases. CT (computed tomography scan) or “cat” scan is another method of neurological scanning that mainly neurologists (doctors who treat disorders that affect the brain, spinal cord and nerves) use. Finally, PET (positron emission tomography) scans are able to both produce images of the brain and monitor how your brain is functioning. PET scans are a type of nuclear medicine, using radioactive substances (usually Oxygen-15) as tracers that detect and measure changes in blood flow in the brain. A combination of problems—including the fact that neither MRI, fMRI, CT, or PET scans are capable of detecting which neurons are firing or able to map all the neurons in a brain—make neuron detection and mapping impossible.

This is where the connectome comes in. The connectome (first coined by two researchers around the same time, independent of each other) is a comprehensive map of neural connections in the brain. You can think of it like a “wiring diagram” for your brain. Unfortunately, there are no full human connectome maps available. The first and only full connectome is of Caenorhabditis elegans, a roundworm. This roundworm is often used in neuroscience research as a benchmark because it has only 302 neurons (compared to the 86 billion in the average human). Another interesting detail is that Caenorhabditis elegans neurons do not fire action potentials* and do not have any voltage-gated sodium channels**.

Unfortunately, at this time, the only way to construct a connectome on the cellular level is microscopic analysis of limited portions of the brain only after death. Other methods are capable of creating an estimated portion of the brain, but are not as accurate and only serve as a comparison. These non-invasive imaging techniques are a combination of DW-MRI (diffusion weighted magnetic resonance imaging) and fMRI. When combined, the two imaging technologies allow realistic reconstruction of the major fiber bundles in the brain and capture the brain’s network activity. Through DW-MRI and fMRI techniques, scientists are able to build structural and functional maps of any organism’s brain.

* when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. In simple terms: an action potential is when an “electric message” fires at around 120 m/s, bringing (in the brain) the charge from -70mc to +40mv. A neuron fires completely or does not fire. This is called the all or none principle.

** membrane proteins that form ion channels, conducting sodium ions through a cell’s plasma membrane. In simple terms: A gate that only opens for certain ions (in this case, Na+) under certain conditions. These gates can also be inactivated, and require action potentials to activate them.

What did you learn?


1. What is the purpose of a voltage-gated sodium channel in a human’s brain?

Voltage-gated sodium channels are a type of sodium channel that controls the initiation and continuation of an action potential. The sodium ions enter the cell’s plasma membrane and allow the ions to flow through the channel, either initiating or continuing an action potential. This effectively allows voltage-gated sodium channels control over nervous system function, muscle contractions and heart rhythm.

2. What is the difference between MRI, DW-MRI and fMRI?

The main and most important difference between MRI, DW-MRI and fMRI is the scanning method. MRI uses a combination of magnetic fields, magnetic gradients, and radio waves to generate images. DW-MRI is a specific set up of MRI sequences in tandem with software to generate images using a diffusion of water molecules to generate contrast and create the resulting images. DW-MRI is also non-invasive, and it is very useful to map tractography.*** fMRI uses blood-oxygen-level dependent contrast, a specialized brain and body scan used to map the neural activity in the brain or spinal cord. It does not require any injections or surgery, and is superior in brain mapping research.

***3D modeling technique used to visually represent nerve tracts using data collected by diffusion MRI.