Glass Brain Project, Adam Gazzaley, UCSF
Glass Brain Project, Adam Gazzaley, UCSF

Flying Through Inner Space

It’s hard to truly see the brain. I don’t mean to simply see a three-pound hunk of tissue. I mean to see it in a way that offers a deep feel for how it works. That’s not surprising, given that the human brain is made up of over 80 billion neurons, each branching out to form thousands of connections to other neurons. A drawing of those connections may just look like a tangle of yarn.

As I wrote in the February issue of National Geographic, a number of neuroscientists are charting the brain now in ways that were impossible just a few years ago. And out of these surveys, an interesting new way to look at the brain is emerging. Call it the brain fly-through. The brain fly-through only became feasible once scientists started making large-scale maps of actual neurons in actual brains. Once they had those co-ordinates in three-dimensional space, they could program a computer to glide through it. The results are strangely hypnotic.

Here are three examples, from the small to the big. (Click on the cog-wheel icon if you can to make sure you’re watching them at high resolution.)

First is a video from a project called Eyewire. Volunteers play a game to map the structure of individual neurons. Here are a handful of neurons from the retina of a mouse. (More details about the video can be found here.)

The second video is a flight through the entire brain of a mouse, made possible by a new method called CLARITY. This method involves first adding chemicals to the brain to wash out the lipids and other chemicals that give it color. The brain is rendered transparent, even though its neurons remain intact.

Next, scientists douse the brain with compounds that only latch onto certain types of neurons, lighting them up. The researchers can then take pictures of the brain from different angles and combine them into a three-dimensional representation of the brain in which you can distinguish individual neurons. In this video, from the lab of Karl Deisseroth at Stanford University, a very common type of neuron is colored. Flying through the brain, we can start to get a feel for the large-scale connections that stretch across it.

And finally, we come to the newest method–one that didn’t even exist when I was working on my article. Adam Gazzaley of the University of California at San Francisco and his colleagues have made it possible to fly through a representation of a thinking human brain–as it thinks.

Here’s how they built this fly-through, which they call the Glass Brain. First, they gave volunteers a high-resolution MRI scan to get a very detailed picture of the overall shape of their brain. MRI doesn’t let you see individual neurons, but it does mark out the major structures of the brain in fine detail.

Next, they added in more anatomy with a method called diffusion tensor imaging. To use this method (known as DTI for short), scientists reprogram MRI scanners to measure the jostling of water molecules inside of neurons. Many of the neurons in the brain are located in the outer layers of the brain, and they extend long fibers across the inner regions and link up to the outer layers at a distant spot. Many of these fibers are organized together in pathways. The water molecules in the fibers jostle back and forth along that pathway, and so scientists can use their movement to reconstruct their shape.

The combination of MRI and DTI gave Gazzaley and his colleagues both the structures of the brain and the pathways connecting them, all lined up in the same three-dimensional space.

Now came the third ingredient: recordings of the brain’s activity. Gazzaley used EEG, a method that involves putting a cap of electrodes on someone’s head and measuring the electrical activity that reaches from the brain up through the skull to the scalp.

EEG is very fast, measuring changes in brain activity at a resolution of a tenth of a second or less. The drawback to EEG is that it’s like trying to eavesdrop on people in the next room over. A lot of detail gets blurred away as the signals travel from their source. To reconstruct the brain’s inner conversations, Gazzaley and his colleagues programmed a computer to solve mathematical equations that allow it to use the scalp recordings to infer where in the brain signals are coming from. Their program also measured how synchronized signals in different regions were with each other. Combining this information with their map of the brain’s pathways, the scientists could reconstruct how signals moved across the brain.

And here’s a video of what they ended up with. In this case, the volunteer was simply asked to open and shut her eyes and open and close her hand.

As gorgeous as this is simply as a video, there’s more to it. It didn’t take Gazzaley’s computer weeks to crunch all the data from the experiment, calculate the sources of the EEG signals and map them onto the brain. The system can create this movie in real time.

Imagine, if you will, putting on an EEG cap and looking at a screen showing you what’s happening in your brain at the moment you’re looking at it. That’s what this system promises.

I called Gazzaley to get the details of this new view of the brain. It took him and his team a year to build and to validate it–that is, to make sure that the patterns in the video have the same features that well-studied imaging technologies have found in the brain. Now Gazzaley hopes to start using it to record data during experiments and to test some prominent ideas about how the brain processes information.

And this imaging may be useful outside the lab. Gazzaley and his colleagues recently designed a video game that improved the cognition of older people. It may be possible to incorporate their new brain display into a game, allowing people to try to alter their brain activity through a kind of neuro-feedback.

Just recently, Gazzaley got another idea. He put an EEG cap on a colleague and then pushed the output to a set of Oculus Rift virtual reality goggles. Gazzaley put the goggles on and then used an Xbox joystick to fly through his colleague’s brain, which he could look at all around him in three dimensions.

“I had never seen a brain inside out before,” Gazzaley told me. “After that I couldn’t get back to work. I had to lay on the grass for a while.”

Tomorrow I will be speaking about brain mapping in Rochester, New York, in their Arts & Lectures series. You can get information about tickets here.