The Man Working To Reverse Engineer Your Brain

The Man Working To Reverse Engineer Your Brain
February 29, 2012 - NPR

Our brains are filled with billions of neurons, entangled like a dense canopy of tropical forest branches. When we think of a concept or a memory — or have a perception or feeling — our brain's neurons quickly fire and talk to each other across connections called synapses.

How these neurons interact with each other — and what the wiring is like between them — is key to understanding our identity, says Sebastian Seung, a professor of computational neuroscience at MIT.

Seung's new book, Connectome: How the Brain's Wiring Makes Us Who We Are, explains how mapping out our neural connections in our brains might be the key to understanding the basis of things like personality, memory, perception and ideas, as well as illnesses that happen in the brain, like autism and schizophrenia.

"These kinds of disorders have been a puzzle for a long time," says Seung. "We can look at other brain diseases, like Alzheimer's disease and Parkinson's disease, and see clear evidence that there is something wrong in the brain."

But with schizophrenia and autism, there's no clear abnormality during autopsy dissections, says Seung.

"We believe these are brain disorders because of lots of indirect evidence, but we can't look at the brain directly and see something is wrong," he says. "So the hypothesis is that the neurons are healthy, but they are simply connected together or organized in an abnormal way."

One current theory, says Seung, is that there's a connection between the wiring that develops between neurons during early infancy and developmental disorders like schizophrenia and autism.

"In autism, the development of the brain is hypothesized to go awry sometime before age 2, maybe in the womb," he says. "In schizophrenia, no one knows for sure when the development is going off course. We know that schizophrenia tends to emerge in early adulthood, so many people believe that something abnormal is happening during adolescence. Or it could be that something is happening much earlier and it's not revealed until you become an adult."

What scientists do know, he says, is that the wiring of the brain in the first three years is critical for development. Infants born with cataracts in poor countries that don't have the resources to restore their eyesight remain blind even after surgery is performed on them later in life.

"No matter how much they practice seeing, they can never really see," says Seung. "They recover some visual function, but they are still blind by comparison to you and me. And one hypothesis is that the brain didn't wire up properly when they were babies, so by the time they become adults, there's no way for the brain to learn how to see properly."

At birth, he says, you are born with all of the neurons you will ever have in life, except for neurons that exist in two specific areas of the brain: the dentate gyrus of the hippocampus, which is thought to help new memories form, and the olfactory bulb, which is involved in your sense of smell.

"The obvious hypothesis [is] that these two areas need to be highly plastic and need to learn more than other regions, and that's why new neurons have to be created — to give these regions more potential for learning," says Seung. "But we don't really have any proof of that hypothesis."

But not everything is set in stone from birth. The complex synaptic connections that allow neurons to communicate with one another develop after babies have left the womb.

"As far as we know, this is happening throughout your life," he says. "Part of the reason that we are lifelong learners — that no matter how old you get, you can still learn something new — may be due to the fact that synapse creation and elimination are both continuing into adulthood."

The neurologist explains how simple visual experiments have changed the lives of his patients.

Connectomes: Reverse Engineering The Brain

Only one organism has had its full connectome — or neural map — mapped out by neuroscientists. It's a tiny worm no bigger than a millimeter, but it took scientists more than a dozen years to map out its 7,000 neural connections. They started out by using the world's most powerful knife and slicing the worm into slices a thousand times thinner than a human hair. They then put each slice in an electron microscope and created a 3-D image of the worm's nervous system. That's when the true labor started, says Seung.

"That's when [neuroscientists had to] go through all these images and trace out the paths taken by all of the branches of the neurons and find the synapses, and compile all that information to create the connectome," he says.

Each of the worm's 300 neurons had between 20 and 30 connections. In comparison, humans have 10,000 comparisons of neurons — and billions of neurons. And scientists still aren't sure what the various pathways in a worm's nervous system mean.

"We're still far away from understanding the worm," says Seung. He says that scientists would like to eventually map a 1-millimeter cube of a human brain or a mouse brain, which contains 100,000 neurons and a billion connections.

"The imaging of all of those slices of brain can be automated and made much more reliable," he says. "And now we have computers that are getting better at seeing."

So far, though, neuroscientists have only mapped the neural connections of a piece of a mouse retina, which is very thin.

"What we know in the retina is a catalog of the types of neurons," he says. "The next challenge is to figure out what are the rules of connection between these types of neurons. And that's where we still don't know a whole lot."

Mapping more of these connections, he says, will tell us a lot about brain function and possible pathways that can be treated.

"I don't want to promise too much, and my goal right now is simply to see what is wrong," he says. "That's not in itself a cure. But obviously it's a step toward finding better treatments. The analogy I make is the study of infectious diseases before the microscope. You could see the symptoms, but you couldn't see the microbes — the bacteria that caused disease. We're in an analogous stage with mental disorders. We see the symptoms, but we don't have a clear thing we can look at in the brain and say, 'This is what's wrong.' "
Sebastian Seung is a professor of computational neuroscience at MIT and an investigator at the Howard Hughes Medical Institute.

Sebastian Seung is a professor of computational neuroscience at MIT and an investigator at the Howard Hughes Medical Institute.

On connectomes

"A connectome is a map between neurons inside a nervous system. You can imagine it as being like the map that you see in the back of the pages of in-flight magazines. Imagine that every city in that map is replaced by a neuron and every airline route between cities is replaced by a connection."

On the Jennifer Aniston neuron

"Sometimes people with seizures don't respond well to medications, and the only way for them to respond is for surgeons to remove the part of the brain from which the seizures originate. So [a computational neuroscientist] got permission to also record the signals of single neurons inside human subjects before doing the operating. So what the experimenters did was they showed the people pictures of celebrities and places and other kinds of objects, and they found that the neurons in the areas that they recorded from, which is in the medial temporal lobe ... responded highly selectively. They would respond to only a few pictures out of a large collection of many pictures. And in particular, there was one neuron in one person that responded only to pictures of Jennifer Aniston — not to Halle Berry, not to Julia Roberts, and one great finding said that this neuron did not respond to pictures of Jennifer Aniston with Brad Pitt. ... It would be overstating the case to say this neuron only responds to Jennifer Aniston because the experimenters didn't have time to show the person all possible celebrities. But it seems safe to say that this neuron responds to only a small fraction of celebrities."
A diffusion spectrum image shows the brain wiring in a healthy human adult.
NIMH/MGH/Harvard U.

A diffusion spectrum image shows the brain wiring in a healthy human adult.

On neural networks

"Your brain is this vast network of neurons, communicating through signals. And as far as neuroscientists can tell, these signals that are passed around the network are reflecting the processing of all of our mental processes — your thoughts, your feelings, your perceptions and so on."

On regenerative neurons

"If you have brain damage, and lots of neurons are killed, those neurons won't grow back except in [the dentate gyrus of the hippocampus, which is thought to help new memories form, and the olfactory bulb, which is involved in sense of smell]. So you could view it from a very pessimistic viewpoint. On the other hand, it's entirely possible that medical advances in the future will somehow activate regenerative powers in the brain. If these regenerative powers exist in [those] two areas, why not awaken them in other areas of the brain? So there's also an optimistic kind of spin on this."

Read an excerpt of Connectome

Introduction

No road, no trail can penetrate this forest. The long and delicate branches of its trees lie everywhere, choking space with their exuberant growth. No sunbeam can fly a path tortuous enough to navigate the narrow spaces between these entangled branches. All the trees of this dark forest grew from 100 billion seeds planted together. And, all in one day, every tree is destined to die.   This forest is majestic, but also comic and even tragic. It is all of these things. Indeed, sometimes I think it is everything. Every novel and every symphony, every cruel murder and every act of mercy, every love affair and every quarrel, every joke and every sorrow â€" all these things come from the forest.Â

   You may be surprised to hear that it fits in a container less than one foot in diameter. And that there are seven billion on this earth. You happen to be the caretaker of one, the forest that lives inside your skull. The trees of which I speak are those special cells called neurons. The mission of neuroscience is to explore their enchanted branches â€" to tame the jungle of the mind (see Figure 1).   Neuroscientists have eavesdropped on its sounds, the electrical signals inside the brain. They have revealed its fantastic shapes with meticulous drawings and photos of neurons. Their discoveries are amazing, but from just a few scattered trees, can we hope to comprehend the totality of the forest?   In the seventeenth century, the French philosopher and mathematician Blaise Pascal wrote about the vastness of the universe:

         Let man contemplate Nature entire in her full and lofty majesty; let him put far from his sight the         lowly objects that surround him; let him regard that blazing light, placed like an eternal lamp to           illuminate the world; let the earth appear to him but a point within the vast circuit which that star         describes; and let him marvel that this immense circumference is itself but a speck from the           viewpoint of the stars that move in the firmament.

Shocked and humbled by these thoughts, he confessed that he was terrified by “the eternal silence of these infinite spaces.” Pascal meditated upon outer space, but we need only turn our thoughts inward to feel his dread. Inside every one of our skulls lies an organ so vast in its complexity that it might as well be infinite.

   As a neuroscientist myself, I have come to know firsthand Pascal’s feeling of dread. I have also experienced embarrassment. Sometimes I speak to the public about the state of our field. After one such talk, I was pummeled with questions. What causes depression and schizophrenia? What is special about the brain of an Einstein or a Beethoven? How can my child learn to read better? As I failed to give satisfying answers, I could see faces fall. In my shame I finally apologized to the audience. “I’m sorry,” I said. “You thought I’m a professor because I know the answers. Actually I’m a professor because I know how much I don’t know.”

   Studying an object as complex as the brain may seem almost futile. The brain’s billions of neurons resemble trees of many species and come in many fantastic shapes. Only the most determined explorers can hope to capture a glimpse of this forest’s interior, and even they see little, and see it poorly. It’s no wonder that the brain remains an enigma. My audience was curious about brains that malfunction or excel, but even the humdrum lacks explanation. Every day we recall the past, perceive the present, and imagine the future. How do our brains accomplish these feats? It’s safe to say that nobody reallyknows.

   Daunted by the brain’s complexity, many neuroscientists have chosen to study animals with drastically fewer neurons than humans. The worm shown in Figure 2 lacks what we’d call a brain. Its neurons are scattered throughout its body rather than centr