here are all posts tagged as connectome...

Bluebrain: Documenting the Frontiers of Brain Research

In his 2009 TED Talk, Dr. Henry Markram publicly announced the Blue Brain Project, a ten-year initiative to reverse-engineer a fully functional supercomputer-powered simulation of the human brain in ten years. Inspired by such an ambitious project, filmmaker Noah Hutton set about chronicling the progress of Markram’s [blue]brainchild in an independently produced documentary spanning the ten-year timeline—a true-life brain-themed “will-they-won’t-they” story.

On January 28, 2013, the European Commission awarded Henry Markram and his team $1.3 billion for the Human Brain Project.

Since 2009, Bluebrain: the Film has evolved into a 14-year-long documentary-in-the-making. By 2013, the Blue Brain team joined forces with scientists across Europe, receiving $1.3 billion in funding awarded by the European Commission for the Human Brain Project: a unified effort to create the brain simulation under a renewed 10-year timeline. 2013 also marked the official US entry into the quest to understand the human brain, as Obama announced the BRAIN Initiative specifically geared towards developing new neuroscience technologies over the next decade.

To accommodate the growing breadth of brain research, Hutton has widened the film’s scope to include scientists from around the world as they attempt to tackle one of the greatest challenges facing science. Each year, he releases an installment of Bluebrain—an annual “state-of-the-union” for the latest from the field—providing a unique, real-time glimpse into the pace of progress + the process of scientific discovery. Below, you can watch the fourth installment of Bluebrain and enjoy ArtLab’s Q&A for more about the film + his insights into these groundbreaking brainy projects.

Could you talk about how you got started making the film and how the project has evolved since you began in 2009?

I graduated from college as a neuroscience major. At that point, I had already made my first feature-length documentary and knew that I wanted to make films. I was aware of the Blue Brain Project because I had seen Henry Markram’s TED Talk in 2009, when he laid out a ten-year timeline to create a simulation of the brain. It was exciting, but also controversial. And it just hit me that I had become so interested in neuroscience anyway, and I really liked the Seven Up! series where the filmmaker follows the lives of 14 people every seven years. So I thought it would be very interesting to do a longitudinal film about such a lofty goal of ten years to understand the human brain.

I took my first trip to Lausanne to interview Dr. Markram and show him my first film. After that first visit he emailed me and gave me exclusive access to make the film. So that was how it started. Originally I thought I was in it until 2020, but it became 14 years after they re-booted the project this year as the Human Brain Project. So now it’s until 2024/2025.

Initially I was going to focus on The Blue Brain Project and building these brain simulations. I thought it was philosophically interesting if a film would develop as the brain simulation would develop—two parallel entities growing and getting more complex. That is still part of my interest in making the film, but over the years, I’ve realized this is a much bigger topic and that there are a lot more people and countries—especially this year—throwing in their hats to create big consortiums and projects to really tackle this in our lifetime.

On April 2, 2013, the US officially entered the so-called race to understand the human brain when Obama announced the BRAIN Initiative. [Photo credit: AP Photo/Charles Dharapak]

So I started gradually widening the scope of the film, which really started last year when I began interviewing critics of brain simulation in general. Scientists working on the connectome, who have a fundamentally different approach to Markram, were interesting to talk to because they are openly critical of simulating the brain to understand it. It has been eye-opening for me to find these critics and talk to them. To be convinced by them and then go back to Dr. Markram and be re-convinced by him that he is really doing it right. My needle is all over the place in terms of what I believe because I don’t really know enough of the science to know. So whoever I’m with at the moment kind of convinces me.

You’ve been following the evolution of this quest to understand the human brain for four years now. As a documentarian, do you have any ideas at this point of the ideal story you’d like to tell looking ten years down the line?

There are several ideal stories. One of them is that Markram succeeds in his quest and he creates a simulation of a full human brain that can be the first real example of artificial intelligence. That of course is what he set out to do with The Blue Brain Project and it would be this unbelievable moment. So that’s definitely a possible narrative, which would be wild and great for the film. 

On the other hand, it would be just as interesting—and I think just as compelling—if all this hard work happened over this fourteen years of the film, and we’re just not that much closer to creating this simulation. Or we’ve done a big part of it, but it’s not behaving like a human. So failure in how the goal was originally defined would show where we really are in understanding the brain. And it also shows philosophically that it might be much further from that level of understanding in these big projects than we think that we are in how they define their goals and their timelines.

While it ushered us into the genomics age, the decade-long Human Genome Project did little to show us what genes make us human or find cures to common diseases. And a number of parallels have been drawn between the HGP and these brain-focused initiatives. So do you have any insights into what makes these projects different and what we might ultimately learn from them?

The biggest thing I’ve learned in the last two years is that there are fundamentally two different approaches to how we’re going to understand the question of the brain right now, which are nicely represented by the European project on the one hand, and by many of the people involved in the US BRAIN Initiative on the other. The European approach, led by Markram, is reverse engineering a simulation of the human brain that will be able to predict the results of experiments we haven’t even done yet. Markram thinks we can actually learn about most of the brain through this simulation, as opposed to collecting every piece of data in the lab. That is opposed to scientists in the connectome crowd, like Sebastian Seung and Jeff Lichtman, who really believe we don’t know enough yet to predict unknown results. Instead, we have to trace every connection in tissue and collect much more data to understand emergent principles before we go about building a model of the brain.

Some of Markram’s critics argue that before we can understand the brain, we must first create a map—the connectome—of every neural connection in the brain. [Image credit: V.J. Wedeen + L.L. Wald, Martinos Center for Biomedical Imaging at MGH

So it’s hard to generalize what everyone thinks we’re going to get out of this. Henry Markram would say once you have a functional simulation that’s accurate—that you’ve tested at every stop and it behaves just like a real biological system—then you can simulate diseases on the model and model different kinds of treatments. It would be this amazing telescope—a predictive, diagnostic tool—that can look at any potential brain disease or malfunction and come up with a set of solutions. The US approach seems much more geared towards continuing basic science and the way that we already go about solving problems—identifying genes and markers of disease and figuring out on animal models how to treat them.

So those are two different timelines and two different ways of approaching a problem. I’m just so interested that that is the case right now—that we don’t know which way is the best way to move forward in understanding the brain. We are just fundamentally divided between both camps in a sense, even though people from both camps will tell you that they are going to work together very nicely. And in fact, they probably will. That’s the most hopeful scenario—that the brain simulation will be getting all this rich data from the US and the US can use the simulations to tell them which parts of the brain we need to study more. So there is hope for massive scale collaboration that speeds up progress, but we will have to overcome some of the tensions in the field, which of course exist.

As you’ve been expanding the scope of the film, have you considered including the perspectives of nonscientists who have been following these projects?

I want to talk to people who have a firm footing in—or have at least checked out—science and materialism. I’m skeptical of talking to people who reject brain science completely. At the same time, there are philosophers who I think would add good context to the film; philosophers who draw upon neuroscience and are firmly grounded in brain science as a basis for their theorizing, like Paul and Patricia Churchland.

I do want to include other people and perspectives as we go on. The cool thing about filming each year is that—now that I feel I’ve covered the beginning of the project, the critics, and this big year of re-launching—every year I have the opportunity to shift the focus of the piece onto a different part of the story. Whatever is most interesting that year, I can check out. Because it is such a long-term project, if there is nothing major to report on in the development of the science, one year I might just talk to philosophers and have it be a philosophical year.

How has your relationship with Henry Markram changed over the course of the four years you’ve been filming?

When I interviewed him for the first time, I was so nervous. There’s this setting on the camera called “gain”—so if you’re in a really dark room, you pump up the gain and it makes things really grainy, but you can see the room. And I was so nervous that in setting up the camera, I had pumped the gain up to the maximum, and that was how I filmed the first interview. It was a disaster. Luckily the footage was salvageable, but my point is that I went from that to now being super comfortable—I consider him a friend now. It has been a very nice evolution of feeling more and more comfortable.

Navigating a relationship with a subject, especially where they’re watching a little film about themselves each year that you make, is very delicate. That’s such a personal thing to have your image put out into the world. The relationship on that level of the subject to the filmmaker is very dynamic. I’m sensitive to not making them feel uncomfortable—I want them to feel good about what’s out there. But at the same time I need to be independent and objective. It’s really interesting to balance that. There’s no one way to do it, and I have to feel it out every year.

To watch Bluebrain from the beginning + stay tuned for more from the project, be sure to visit the official website. And for Noah’s insights on the intersection between neuroscience + art, check out The Beautiful Brain.

Reading Brainbow

Scientists are story tellers. Biographers of the universe’s constituent components. All of our hypotheses // experiments // theories are aimed at painting a cohesive picture of some phenomenon. At going back and further complicating this picture, seeking to reveal all of its inherent nuances and caveats.

[As their name implies] neuroscientists are constantly pursuing the story of the nervous system, seeking to tell the nerve cell’s tale. our body communicates with itself // with others // with the environment around us via an interconnected and [overwhelmingly] complex network of neurons. All the information transfer required for sentient life occurs along these neuronal tracks.

Tamily Weissman

In an effort to understand how our neurons are connected to one another—to map the informational highways that run through our bodies—Harvard’s Dr. Jeff Lichtman and Dr. Joshua Sanes developed The Brainbow. Believe it or not, the vividly colored image above is no Jackson Pollock! Instead, it is actually a photograph of a mouse’s hippocampus—the part of the brain responsible for spatial navigation and memory—generated by the brainbow technique. What’s more, if we were to take a snapshot of our own human brains using this same method, it would turn out to look very much like the mouse’s above.

the dentate gyrus - the memory making part of our brains. lichtman + sanes 2007.

the dentate gyrus – the memory making part of our brains. lichtman + sanes 2007.

Just as a monitor uses red // green // blue to produce the myriad of colors we see flashing across our television screens, Dr. Lichtman + Dr. Sanes’s brainbow use orange // green // red // cyan *fluorescent proteins* to produce brilliantly colored images of the brain’s many connections. Its connectome. Each fluorescent protein is coded for by a different gene, with different combinations of these genes expressed in a particular neuron to label the neuronal cell any one of roughly one hundred [!] different colors.

These distinct hues can be detected and traced by a computer so that we may follow a given neuron down its individual color-paved path. By chasing the brainbow, we have the potential to follow this cell as it develops over time. We can track what other cells this neuron talks to. we can observe how different stimuli modulate this cell’s behavior. We can better understand how this cell passes along or receives a given biological message.

As we zoom out, we can begin to trace the neural circuitry of the brain as a whole. with brainbow technology, neuroscientists are now working to construct three-dimensional models [shown in video below] of all the connections in the brain by stacking together fluorescent images of thin sections of the brain. Compiling these glowing neural snapshots have begun to untangle and illuminate the mysteries behind how we are wired.