Monday, December 22, 2014

Why are scientists trying to map every single neuron in the brain?

A computer diagram of neural connections in the mouse brain, part of the most extensive mammal brain map ever. Allen Institute for Brain Science

Researchers around the world are engaged in a massively difficult project to map the entire human brain. And recently, they have been reporting some promising advances.

The ultimate goal is to chart the locations of the roughly 85 billion neurons in the brain, their roughly 100 trillion connections, and how they all function.

If that sounds like a tall order, it's because it is. The hope is that doing this will lead to a far greater understanding about how brains work and especially how mental disorders come about — and could be better treated.

Below is a very basic primer on why scientists are mapping the human brain and how they go about doing it:

Who's doing the mapping?

This isn't one big, organized project. It's a bunch of scientists across the world working on various undertakings.

There's a lot of excitement about brain mapping right now. The US and the EU recently dumped some significant money into the mix. Obama's BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies) funding started in 2014 and should provide $100 million a year for each of 10 years. (For comparison, the National Institutes of Health neuroscience budget is about $5.5 billion a year.) The European Commission has promised $1.3 billion over 10 years to make a detailed computer model of the human brain. Many private projects are also underway.

Is it hard to map a human brain?

Yes. The human brain is extremely complex. Different people's brains have cells connected in different ways, so researchers can't just map one brain and call it a day. In addition, contrary to previous scientific thought, everyone's brain develops new cells and new connections throughout life. If you're alive, your brain is changing.

So how do you map a brain?

One way is to start with less complex organisms. The only species that's had every single neuron mapped out is a microscopic worm called C. elegans. This was a lot easier, since the worm has only 302 neurons. (That's 0.0000004 percent the number of neurons in a human brain.)

But researchers are working on mammals' brains, too. For example, the Allen Mouse Brain Connectivity Atlas is the most detailed connection map of any mammal's brain. One technique they're using to figure it out is adding a fluorescent protein to a tiny area with about 100 to 500 neurons. And then they track where the glowing protein flows. And how do they do that? Well, they remove the mouse brains afterward and chop them up into tiny pieces. Then they repeat again with a different mouse and an injection into a different spot. When researchers published a major paper on the atlas in April, they'd mapped roughly 15 to 20 percent of all mouse-brain neurons.

Is a human brain more difficult to map than a mouse brain?
Diffusion tensor imaging of brain

Tracking water flow to trace neurons. (Thomas Schultz/Wikimedia Commons)

Yes. We can't really put fluorescent proteins inside humans and then take out their brains to see where the glowing went. So, instead, scientists use other techniques including a type of MRI that tracks water flow in brain tissue. It's usually easier and faster (not to mention less expensive) to study thousands of mice than thousands of people, and resolution is always an issue.

So we just need to find the neurons' connections, and we're done?

Not exactly. Researchers compare mapping the brain's connections to mapping a city's roads: you know where the streets are but have no idea what the traffic is like.

So another major area of brain mapping has been documenting where different genes are turned on. For example, an Allen Institute for Brain Science study in April tracked the locations of genetic activity in brains from four human fetuses. The researchers looked at tens of thousands of genes during a key time when areas are developing that handle higher-order functions such as reasoning and memory.

Another big task is studying which neurons are firing when. The most impressive work on this so far might be a study published in the spring of 2014. In it, researchers individually turned on each of 1,054 different neuronal circuits in fruit-fly larvae and then recorded what behaviors happened for every single one. Please note: fruit-fly larvae are simple creatures with only 10,000 neurons and with behaviors far simpler than humans'. (The researchers classified 29 total "general behaviors" in the larvae such as "turn-avoid" or "back up." Humans have a few more than that.)

Scientists are currently mapping brain function in humans at a much rougher level, using equipment such as high-resolution fMRI machines. For a great overview of brain-function mapping in people, check out this story in the New York Times.

How long will it take to map a human brain?

A long time. Researchers needed four years to plot the main routes (about 15 to 20 percent) of the roughly 75 million neurons in the mouse brain. By contrast, the human brain has about 85 billion neurons — about 1,100 times as many as a mouse. Hongkui Zeng, who plays a big role in the Allen Institute's mouse-atlas project, told me that a human-brain connection map with a similar resolution as the mouse one "can be done within the next 10 years." But that would still be a small fraction of the entire human brain.

So, yeah. It's a long haul. But that doesn't mean it's pointless. Here's a piece by Ben Thomas at Scientific American Mind on why trying but failing is still worth it, how terribly complex the task is, and why heading toward "less wrongness" in our understanding of the brain is still incredibly useful.

What do we do once we have a brain map?

All kinds of things. Maybe we could make brain-like computers that are as creative as we are. Maybe we could figure out exactly what chemical imbalances are going on in people with mental illnesses and how much serotonin (or whatnot) to pump into which parts of the brain to treat them. And maybe we could finally answer questions that are currently in the realm of philosophy —€” What is love? What is beauty? What are dreams?

Further reading

Why trying to map the brain is worth it, even if scientists ultimately fail

Mapping brain function in people

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