Connectome: How the Brain's Wiring Makes Us Who We Are

by Sebastian Seung

Overview

The bold and thrilling quest to finally understand the brain—and along with it our mental afflictions, from depression to autism—by a rising star in neuroscience

Sebastian Seung, a dynamic young professor at MIT, is at the forefront of a revolution in neuroscience. He believes that our identity lies not in our genes, but in the connections between our brain cells—our own particular wiring. Seung and a dedicated group of researchers are leading the effort to map these connections, neuron by neuron, synapse by synapse. It is a monumental effort—the scientific equivalent of climbing Mount Everest—but if they succeed, they will uncover the basis of personality, identity, intelligence, memory, and perhaps disorders such as autism and schizophrenia. Seung explains how this new map of a human “connectome” might even enable us to “upload” our brains into a computer, making us effectively immortal.

Connectome is a mind-bending adventure story, told with great passion and authority. It presents a daring scientific and technological vision for at last understanding what makes us who we are, both as individuals and as a species.

Product Details

ISBN-13:	9780547508184
Publisher:	Houghton Mifflin Harcourt
Publication date:	02/07/2012
Pages:	384
Product dimensions:	6.20(w) x 9.10(h) x 1.30(d)

About the Author

Sebastian Seung is Professor of Computational Neuroscience at MIT and an Investigator of the Howard Hughes Medical Institute. He has made important advances in robotics, neuroscience, neuroeconomics, and statistical physics. His research has been published in leading scientific journals, and also featured in The New York Times , Technology Review , and The Economist .

Read an Excerpt

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 — all these things come from the forest.
   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 — 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 really knows.
   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 centralized in a single organ. Together they form a nervous system containing a mere 300 neurons. That sounds manageable. I’ll wager that even Pascal, with his depressive tendencies, would not have dreaded the forest of C. elegans. (That’s the scientific name for the one-millimeter-long worm.)
   Every neuron in this worm has been given a unique name and has a characteristic location and shape. Worms are like precision machines mass-produced in a factory: Each one has a nervous system built from the same set of parts, and the parts are always arranged in the same way.
   What’s more, this standardized nervous system has been mapped completely. The result — see Figure 3 — is something like the flight maps we see in the back pages of airline magazines. The four-letter name of each neuron is like the three-letter code for each of the world’s airports. The lines represent connections between neurons, just as lines on a flight map represent routes between cities. We say that two neurons are “connected” if there is a small junction, called a synapse, at a point where the neurons touch. Through the synapse one neuron sends messages to the other.
   Engineers know that a radio is constructed by wiring together electronic components like resistors, capacitors, and transistors. A nervous system is likewise an assembly of neurons, “wired” together by their slender branches. That’s why the map shown in Figure 3 was originally called a wiring diagram. More recently, a new term has been introduced — connectome. This word invokes not electrical engineering but the field of genomics. You have probably heard that DNA is a long molecule resembling a chain. The individual links of the chain are small molecules called nucleotides, denoted by the letters A, C, G, and T. Your genome is the entire sequence of nucleotides in your DNA, or equivalently a long string of letters drawn from this four-letter alphabet. Figure 4 shows an excerpt from the three billion letters, which would be a million pages long if printed as a book.
   In the same way, a connectome is the totality of connections between the neurons in a nervous system. The term, like genome, implies completeness. A connectome is not one connection, or even many. It is all of them. In principle, your brain can also be summarized by a diagram that is like the worm’s, though much more complex. Would your connectome reveal anything interesting about you?
   The first thing it would reveal is that you are unique. You know this, of course, but it has been surprisingly difficult to pinpoint where, precisely, your uniqueness resides. Your connectome and mine are very different. They are not standardized like those of worms. That’s consistent with the idea that every human is unique in a way that a worm is not (no offense intended to worms!).
   Differences fascinate us. When we ask how the brain works, what mostly interests us is why the brains of people work so differently. Why can’t I be more outgoing, like my extroverted friend? Why does my son find reading more difficult than his classmates do? Why is my teenage cousin starting to hear imaginary voices? Why is my mother losing her memory? Why can’t my spouse (or I) be more compassionate and understanding?
   This book proposes a simple theory: Minds differ because connectomes differ. The theory is implicit in newspaper headlines like “Autistic Brains Are Wired Differently.” Personality and IQ might also be explained by connectomes. Perhaps even your memories, the most idiosyncratic aspect of your personal identity, could be encoded in your connectome.
   Although this theory has been around a long time, neuroscientists still don’t know whether it’s true. But clearly the implications are enormous. If it’s true, then curing mental disorders is ultimately about repairing connectomes. In fact, any kind of personal change — educating yourself, drinking less, saving your marriage — is about changing your connectome.
   But let’s consider an alternative theory: Minds differ because genomes differ. In effect, we are who we are because of our genes. The new age of the personal genome is dawning. Soon we will be able to find our own DNA sequences quickly and cheaply. We know that genes play a role in mental disorders and contribute to normal variation in personality and IQ. Why study connectomes if genomics is already so powerful?
   The reason is simple: Genes alone cannot explain how your brain got to be the way it is. As you lay nestled in your mother’s womb, you already possessed your genome but not yet the memory of your first kiss. Your memories were acquired during your lifetime, not before. Some of you can play the piano; some can ride a bicycle. These are learned abilities rather than instincts programmed by the genes.
   Unlike your genome, which is fixed from the moment of conception, your connectome changes throughout life. Neuroscientists have already identified the basic kinds of change. Neurons adjust, or “reweight,” their connections by strengthening or weakening them. Neurons reconnect by creating and eliminating synapses, and they rewire by growing and retracting branches. Finally, entirely new neurons are created and eliminated, through regeneration.
   We don’t know exactly how life events — your parents’ divorce, your fabulous year abroad — change your connectome. But there is good evidence that all four R’s — reweighting, reconnection, rewiring, and regeneration — are affected by your experiences. At the same time, the four R’s are also guided by genes. Minds are indeed influenced by genes, especially when the brain is “wiring” itself up during infancy and childhood.
   Both genes and experiences have shaped your connectome. We must consider both historical influences if we want to explain how your brain got to be the way it is. The connectome theory of mental differences is compatible with the genetic theory, but it is far richer and more complex because it includes the effects of living in the world. The connectome theory is also less deterministic. There is reason to believe that we shape our own connectomes by the actions we take, even by the things we think. Brain wiring may make us who we are, but we play an important role in wiring up our brains.
   To restate the theory more simply:
   You are more than your genes. You are your connectome.

 

Table of Contents

Introduction • ix Part I: Does Size Matter?
 1 Genius and Madness • 3
 2 Border Disputes • 22
Part II: Connectionism
 3 No Neuron Is an Island • 39
 4 Neurons All the Way Down • 60
 5 The Assembly of Memories • 76
Part III: Nature and Nurture
 6 The Forestry of the Genes • 99
 7 Renewing Our Potential • 116
Part IV: Connectomics
 8 Seeing Is Believing • 137
 9 Following the Trail • 155
 10 Carving • 170
 11 Codebreaking • 185
 12 Comparing • 201
 13 Changing • 216
Part V: Beyond Humanity
 14 To Freeze or to Pickle? • 233
 15 Save As . . . • 254
Epilogue • 274
Acknowledgments • 277
Notes • 279
References • 314
Figure Credits • 335
Index • 336

What People are Saying About This

From the Publisher

Wall Street Journal's 10 Best Nonfiction Books of 2012

Amazon's Top 100 Editor's Picks for 2012

Publishers Weekly Top Ten in Science for Spring 2012

“The best lay book on brain science I’ve ever read.”
— Wall Street Journal by Daniel Levitin , Professor, McGill University; author of This Is Your Brain on Music and The World in Six Songs.

“‎This is complicated stuff, and it is a testament to Dr. Seung’s remarkable clarity of exposition that the reader is swept along with his enthusiasm, as he moves from the basics of neuroscience out to the farthest regions of the hypothetical, sketching out a spectacularly illustrated giant map of the universe of man.”
— New York Times

“[A] bracing, mind-expanding report from neuroscience’s razor edge. Accessible, witty, [e]minently logical and at times poetic, Connectome establishes Seung as an important new researcher, philosopher and popularizer of brain science. It puts him on par with cosmology’s Brian Greene and the late Carl Sagan.”
— Cleveland Plain Dealer

“Seung argues intelligently and powerfully that the self lies in the totality of the brain’s wiring.”
— Nature by Christof Koch , Professor, California Institute of Technology; Chief Scientific Officer, Allen Institute for Brain Science; author of Quest for Consciousness and Consciousness: Confessions of a Romantic Reductionist

“With the first-person flavour of James Watson’s Double Helix—an account of how DNA’s structure was discovered—Connectome gives a sense of the excitement on the cutting edge of neuroscience.”
— NewScientist by Terry Sejnowski, Professor and Director, Computational Neurobiology Lab, Salk Institute; Investigator, Howard Hughes Medical Institute; Member, National Academy of Sciences and National Academy of Engineering USA.

“An elegant primer on what’s known about how the brain is organized and how it grows, wires its neurons, perceives its environment, modifies or repairs itself, and stores information. Seung is a clear, lively writer who chooses vivid examples.”
— Washington Post

“Sebastian Seung scales the heights of neuroscience and casts his brilliant eye around, describing the landscape of its past and boldly envisioning a future when we may understand our own brains and thus ourselves.”
—Kenneth Blum, Executive Director, Center for Brain Science, Harvard University

“Sebastian Seung can do it all. He’s widely recognized as a superb physicist, a whiz with computers, and a path-breaking neuroscientist. Connectome shows that he's also a terrific writer, as inspiring as he is clear and good humored.” 
—Steven Strogatz, Cornell University, author of Sync: the Emerging Science of Spontaneous Order

“In Connectome, Sebastian Seung reminds us that the human brain has contemplated itself for centuries. This is an important book, full of refreshingly new science and engaging history, about the essential quest to understand ourselves.”
—Phillip A. Sharp, MIT, 1993 Nobel Prize in Physiology or Medicine

“A landmark work, gorgeously written. No other researcher has traveled as deeply into the brain forest and emerged to share its secrets.”
—David Eagleman, author of Incognito and Sum

“Connectomics is emerging as a crucial and exhilarating field of study. Sebastian Seung takes you by the hand and shows you why. Connectome is a page turner—a book that should be read by anyone who lays claim to be thinking about the nature of life.”
—Michael Gazzaniga, University of California at Santa Barbara and author of Human and The Ethical Brain

Editorial Reviews

Identity. It's not in our genes, argues hugely upcoming MIT neuroscientist Seung, but in the connections among our brain cells. Seung leads a team that aims to map these connections, neuron by neuron, in an effort to disclose the basis of personality, intelligence, and memory and perhaps also the cause of conditions like schizophrenia. Seung writes for rags like the New York Times and the Economist, so he knows how to craft prose that won't be daunting to nonscientists. In fact, I've checked him out; he's a lucid communicator whose well-wrought imagery effectively explains complex issues. Important reading, even for science sissies.

Library Journal

The key to understanding how brains work, writes Seung (Computational Neuroscience/MIT), is in the wiring. The author champions the study of "connectomes," the unique wiring diagrams of individual brains. However, we are barely at the connectome threshold. Indeed, if nothing else, Seung's text is a convincing sales pitch for more funding. The goal would be to map all the synapses that all the neurons in the brain make with other neurons near or far. With such data we should be able to trace what memories look like; we could see how inputs from lower-order neurons feed into a single neuron that enables you to, say, recognize a celebrity. Comparing connectomes from normal vs. disordered brains might reveal faulty wiring that could explain schizophrenia or autism. These and other long-sought explanations of mental faculties are what "connectomics" promises. Moreover, we could see how experience changes the brain, through the "four R's--reweighting, reconnection, rewiring, and regeneration." Seung ably reviews the history of brain mapping, from the 19th-century phrenologists to the pioneers who associated regional brain damage with the loss of specific functions. There are newer technologies in electron and light microscopy that can slice the brain and capture serial neuronal images, and scientists are at work mapping the brains of roundworms and mice. But even if technology comes to the rescue, would it suffice? Seung ignores the role of the abundant glial cells, once thought of as supporting cells but which interact and affect neuronal behavior. The author's final chapters on those seeking immortality by postmortem brain freezing or uploading their brains to a computer seem like sci-fi padding to the text. Expect to hear more about connectomics as the field develops. Meanwhile, enjoy Seung's book as a solid primer on brain physiology and the history of brain mapping.

Kirkus Reviews

Wall Street Journal's 10 Best Nonfiction Books of 2012

Amazon's Top 100 Editor's Picks for 2012

Publishers Weekly Top Ten in Science for Spring 2012

“The best lay book on brain science I’ve ever read.”
— Wall Street Journal by Daniel Levitin, Professor, McGill University; author of This Is Your Brain on Music and The World in Six Songs.

“‎This is complicated stuff, and it is a testament to Dr. Seung’s remarkable clarity of exposition that the reader is swept along with his enthusiasm, as he moves from the basics of neuroscience out to the farthest regions of the hypothetical, sketching out a spectacularly illustrated giant map of the universe of man.”
— New York Times

“[A] bracing, mind-expanding report from neuroscience’s razor edge. Accessible, witty, [e]minently logical and at times poetic, Connectome establishes Seung as an important new researcher, philosopher and popularizer of brain science. It puts him on par with cosmology’s Brian Greene and the late Carl Sagan.”
— Cleveland Plain Dealer

“Seung argues intelligently and powerfully that the self lies in the totality of the brain’s wiring.”
— Nature by Christof Koch, Professor, California Institute of Technology; Chief Scientific Officer, Allen Institute for Brain Science; author of Quest for Consciousness and Consciousness: Confessions of a Romantic Reductionist

“With the first-person flavour of James Watson’s Double Helix—an account of how DNA’s structure was discovered—Connectome gives a sense of the excitement on the cutting edge of neuroscience.”
— NewScientist by Terry Sejnowski, Professor and Director, Computational Neurobiology Lab, Salk Institute; Investigator, Howard Hughes Medical Institute; Member, National Academy of Sciences and National Academy of Engineering USA.

“An elegant primer on what’s known about how the brain is organized and how it grows, wires its neurons, perceives its environment, modifies or repairs itself, and stores information. Seung is a clear, lively writer who chooses vivid examples.”
— Washington Post

“Sebastian Seung scales the heights of neuroscience and casts his brilliant eye around, describing the landscape of its past and boldly envisioning a future when we may understand our own brains and thus ourselves.”
—Kenneth Blum, Executive Director, Center for Brain Science, Harvard University

“Sebastian Seung can do it all. He’s widely recognized as a superb physicist, a whiz with computers, and a path-breaking neuroscientist. Connectome shows that he's also a terrific writer, as inspiring as he is clear and good humored.” 
—Steven Strogatz, Cornell University, author of Sync: the Emerging Science of Spontaneous Order

“In Connectome, Sebastian Seung reminds us that the human brain has contemplated itself for centuries. This is an important book, full of refreshingly new science and engaging history, about the essential quest to understand ourselves.”
—Phillip A. Sharp, MIT, 1993 Nobel Prize in Physiology or Medicine

“A landmark work, gorgeously written. No other researcher has traveled as deeply into the brain forest and emerged to share its secrets.”
—David Eagleman, author of Incognito and Sum

“Connectomics is emerging as a crucial and exhilarating field of study. Sebastian Seung takes you by the hand and shows you why. Connectome is a page turner—a book that should be read by anyone who lays claim to be thinking about the nature of life.”
—Michael Gazzaniga, University of California at Santa Barbara and author of Human and The Ethical Brain

From the Publisher