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.”
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 connections 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.’ ”
Neurobiology and Behavior
Our brains, the ultimate product of millions of years of evolution, are what make us human. But over the past few decades, scientists have discovered that many chemicals in our environment threaten the integrity of our brains. Thousands more have never been studied for their effects. We know some of the outcomes: reduced intelligence and cognitive function, increased antisocial tendencies, impaired senory and motor function, and elevated risks of neurodegenerative disorders such as Parkinson’s disease.
Most of these chemicals are ubiquitous and persistent. We are exposed throughout our lifetimes. But some periods of life are more vulnerable than others. Early development is an especially perilous time for exposure to toxic chemicals. The brain is exquisitely sensitive during this period because of the many paths by which it expands and differentiates on the path to maturity. Cells divide and proliferate; they migrate to specific target areas; they grow connections to other cells to form massive neural networks; neurotransmitter systems take root. All these processes are candidates for interference by toxic chemicals. All are reflected in neurobehavioral outcomes that can be measured when organisms mature to a stage at which they can be tested by procedures that are sensitive to such interference. Late in life, we enter another period of enhanced vulnerability. We are not as able as during earlier periods to compensate for toxic processes and many of our organ systems operate at diminished capacity. It is also a period when these reduced capacities may begin to reflect the damage inflicted earlier in life.
My own research aims to relate behavioral measures to neurotoxicant exposure. Behavioral research occupies a special role in safety assessment because it offers the ability to trace changes in function as organisms mature and age. Among the endpoints of salient interest to regulatory agencies such as EPA and to chemical and pharmaceutical manufacturers are learning capacity, other aspects of cognitive capacity, motor and sensory performance, and differences between males and females.
My efforts have spanned a variety of agents: metals such as mercury and manganese; solvents such as toluene and methanol; air pollutants such as ozone; adventitious contaminants such as dioxin; and endocrine disruptors, which include common ingredients in consumer products such as phthalates.
For more on Bernard Weiss and his research see below.
School of Medicine & Dentistry
Molecular Toxicology & Environmental Medicine Cluster
Ph.D. Program in Toxicology
Professor of Environmental Medicine
Environmental Health Sciences Center,
and Center for Reproductive Epidemiology.
B.A. 1949 (New York University)
Ph.D. 1953 (University of Rochester)