(Ed note: My dad, Henri Montandon, died on Monday night in his home in Walnut Creek, California. As this story suggests, he was a fascinating, curious, unique, intensely smart, wonderful, loving, and sometimes difficult guy. I'm just grateful I knew him as long and as well as I did. To honor his life and work, we're republishing this piece he wrote in March 2013. And to our readers and to families everywhere: Happy Thanksgiving. Hold on to those you love.—Maccabee Montandon)
Before personal computers, some brain maps were made from plastic and glue. My first neuroscience lab was in the dank basement of my home in Baltimore in 1972. A sizable plastic salad bowl served as the brain’s cortex. Other parts were cut from Plexiglas. I didn’t have a clue how the parts should be wired together in order to signal one another. (Nobody did.) But it was obvious that if I scaled the model correctly, using very thin wire to represent neurons, it would be bigger than the basement. It would be bigger than our whole two-story house. In fact, it would be about the size of the Baltimore Orioles' stadium.
These days, I'm far from alone in my enthusiasm for the pursuit. Brain mapping has recently gained serious global traction—most prominently with the Obama Administration's intention of spending 10 years and many millions of dollars to do for the brain what the Human Genome Project did for genetics, and a $1.29 billion European Union mapping mission.
Brain mapping is as old as civilization. Although the earliest use of the term "brain" is in the Edwin Smith Papyrus circa 4,200 BC, it was Aristotle who recorded the first articulated model that represented the human brain as more than an undifferentiated bowl full of jelly. His model had three easily visualized parts: small brain, large brain, spinal cord. Now, after 6,000 years of cutting, looking, comparing, and considering, there are 10 established parts.
Why is it so difficult to map the brain? Robert Sapolsky, a Stanford Professor of Biological, Neurology, and Neurological Sciences and a MacArthur Fellow, has said: "We still know squat about how the brain works." Could the roughly 55,000 neuroscientists who publish 3,000 papers a week really have contributed so little? Sapolsky is being provocative, of course, but I interpret his remark to mean that we have compiled a tremendous midden of brain facts, which highlight how little we actually understand about how the brain does what it does.
With these latest efforts, that appears to be changing. I believe there are two main reasons why brain mapping is freshly in the air: 1. We have great new tools to observe, not only the visual content of the brain, but the electrical, magnetic, and chemical, too. 2. As Larry W. Swanson, a world-class neuroanatomist at the University of Southern California, has suggested, we want to find a compelling reason why the 10 basic structures group together. Hell, we want to know how the whole three-pound ball of fat works.
Understanding how a normal brain functions would take us a long way toward finding cures for severe and persistent mental illnesses—schizophrenia, post-traumatic stress disorder, clinical depression, among them—as well as devastating neurological illnesses such as Alzheimer’s, multiple sclerosis, and Lou Gehrig’s disease. We would be able to enhance normal brain functioning; improve memory, enhance learning, tune fine motor skills. And as Buckminster Fuller once noted, a good place to start when attempting to understand a whole system is by visualizing it.
I know what Bucky means. Sixteen years ago, on my 50th birthday, I pledged to devote much of my remaining years to studying the brain. Sure, I sliced up the ritual cadaver in medical school, but that was a long time ago. So in order to begin, I did what any of us might do: I Googled "human brain map." I was interested in a simple beginning. I wanted a map with the major brain structures and the neurons connecting them. I wanted those neurons to be color coded according to the kind of signaling chemical (aka neurotransmitter or neuroregulator) they used. I wanted the location of the receptors that these neurons connect to. Instead, what I found was an ominous caesura in the neuroscience database, like a large blind spot in your visual field.
I should emphasize here that even the meaning of the term "brain mapping" has changed in the 13 years since I completed my own brain map. There are still two-dimensional maps (like mine) that are similar in kind to maps you find in many atlases. But now, a better term is "brain representation." The squiggly patterns of the EEG and SQUID, fMRI’s colored snapshots of the brain cell’s (or neuron’s) input and processing, even the mammoth Blue Brain project—all of these and many more and different techniques are considered brain mappings.
These days, there are so many maps of such astonishing detail that simply picking out the kind of brain to study is almost as complicated as deciding on a health insurance policy. Just as quantum mechanics has its model system (the hydrogen atom) and biochemistry has its model molecule (hemoglobin), the very first model organism for neuroscience appeared on the scientific stage in 1963, when Dr. Sydney Brenner became enamored of a short (1 mm), transparent, prodigiously fecund nematode named Caenorhabditis elegans, but which most people call C. elegans. The worm does not have a brain, but all of its 302 neurons have been mapped anatomically and functionally and shown to be a small-world network. There are at least 16 websites devoted to maps of C. elegans. Here you can see renderings of every neuron, its structure and function. Of course, intense study of one organism is not without its perils. Dr. Cornelia I. Bargmann was a worm-head for over two decades when she told a New York Times reporter how a colleague had complimented her: "(He) told me that my great strength as a scientist was that I could think like a worm."
But back to my antiquated mapping effort. By 1995 I was living in northern California, and we'd left the dark ages behind—home computers were here. Using AutoCAD, the pre-eminent computer drafting program at the time, I had the computational equivalent of a diesel locomotive to arrange the data. It turned out that a design like an integrated circuit architecture worked well both graphically and quasi-anatomically. The biggest problem was that no one had organized the kind of data I needed in a central archive. (Now there are scores of them.) With the help of a quite patient research librarian at the University of California, San Francisco, I spent years collecting the journal articles where the information was still interred, and digging it out, spoonful by spoonful.
The Human Brain Map 1.0 (available for free download here) arrived in the world after a five-year gestation. A close friend remarked on my monkish existence during that time. The smallest size that preserves the resolution of the hundreds of pathways is 47 inches by 67 inches. Since AutoCAD is a vector graphics program, I also printed it on a T-shirt: "This is your brain on a T-shirt." Anyone who wishes to paint it on the side of their building is free to do so.
My map depicts 120 cortical sites, 400 subcortical sites, 1,400 unique neuronal paths for 46 neurotransmitters, and 4,500 receptors. No one knows for sure the average number of neurons in the human brain. In 2012, Brazilian scientist Dr. Suzana Herculano-Houzel downgraded the "100 billion neuron myth," finding an average of 86 billion neurons in four adult brains. By this reckoning, my map portrays 0.000000016% of the neurons in an average adult brain. (If each of the 86 billion neurons were represented by a ping-pong ball, you could build a cube 904,882 miles on a side out of them. Somewhere within this gargantuan structure would be the 1,400 ping-pong balls representing the neurons in my map.) This suggests to me that certain Swiss mappers are or soon will be bekloppt.
Before I get back to the lab, I'd like to quickly talk about another kind of brain mapping, because the finding is potentially a game changer. It is focused not on a whole brain but on a single neuron. The work was done by researchers Dorian Aur at Barrow Neurological Institute and Mandar Jog at the University of Western Ontario. The neuron, propagating an electro-chemical signal, is thought to carry the signals the brain turns into data, information, knowledge, and sometimes, wisdom.
A classic analogy is that a neuron works like a toilet. Flush the toilet, and the tank empties in a surge, which in neuronal terms is the action potential. Then there is a pause while the toilet tank fills. This is the refractory period. The problem for decades has been that you can study the action potential any way you like, and you cannot account for more than 50% or so of the information entering the brain. Aur and Jog, using a four-pronged electrode, have accounted for about 70% of the information. This is like discovering that you can get to the East by sailing West.
The strangest thing about brain mapping is how it has changed biology. Not long ago, biologists were considered too stupid or lazy to learn math and incapable of devising testable hypotheses. (Or was that just how I thought of them?) When the thundering herd of physicists was discovering new "fundamental" particles every week, Nobel Laureate Enrico Fermi said caustically, "If I could remember the names of all these particles, I would be a botanist." It was not a compliment. Biologists collected things and classified them. End of story.
Now, we still know squat about how the brain works. But for the first time, we know how to know. The mysteries of cognition—perception, thinking, memory, anticipation, creativity—will likely be solved within two decades. Even consciousness, which for a century has been a scientific taboo and the path to professional oblivion, is being studied by serious people who feel it will be understood in the ever progressing manner of space, time, matter, and energy. Biology has become the science that includes all others. Neurobiology may turn the traditional scientific hierarchy on its head so that it, not physics, is the foundation. In other words, we've come a long way from plastic salad bowls in the basement.
In 1974 Henri Montandon received a PhD in clinical psychology from Columbia University, and in 1984 he was awarded an MD from the University of Maryland, Baltimore. For the past 17 years he has done research in theoretical neurobiology in collaboration with several well-known neuroscientists. And yes, he is the dad of Fast Company's Mac Montandon.
[Scientist: Algabafoto via Shutterstock]