July 16, 2019

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How the Brain's Wiring
Makes Us Who We Are

by Sebastian Seung.
Houghton Mifflin Harcourt,
2012 (i-xxii, 359 pages)

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    [1] Genius and madness (3-21)

    [2] Border disputes (22-35)
    [3] No neuron is an island (39-59)

    [4] Neurons all the way down (60-75)

    [5] The assembly of memories (76-95)
    [6] The forestry of genes (99-115)

    [7] Renewing our potential (116-133)
    [8] Seeing is believing (137-154)

    [9] Following the trail (155-169)

    [10] Carving (170-184)

    [11] Codebreaking (185-200)

    [12] Comparing (201-215)

    [13] Changing (216-229)
    [14] To freeze or to pickle? (233-253)

    [15] Save as ... (254-273)
EPILOGUE (274-276)


NOTES (279-313)

REFERENCES (314-334)


INDEX (337-359)

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AUTHOR NOTE = Sebastian Seung is Professor of Computational Neuroscience and Physics at the Massachusetts Institute of Technology (MIT) and formerly worked at Bell Laboratories. He received his Ph.D. in theoretical physics from Harvard University. He has made important advances in robotics, neuroscience, neuroeconomics, and statistical physics.

His research on artificial intelligence and neuroscience has been published in leading scientific journals, and also featured in the New York Times, Technology Review, and the Economist. His laboratory at MIT is currently inventing technologies for mapping connections between the brain's neurons, and investigating the hypothesis that we are all unique because we are "wired differently." Visit Amazon's Sebastian Seung Page.

SUMMARY = The audacious effort to "map" the brain --- and along with it our mental afflictions, from autism to schizophrenia --- by a rising star in neuroscience. We know that each of us is unique, but science has struggled to pinpoint where, precisely, our uniqueness resides. Is it in our genes? The structure of our brains? Our genome may determine our eye color and even aspects of our personality. But our friendships, failures, and passions also shape who we are. The question is: how? Sebastian Seung, a dynamic professor at MIT, is on a quest to discover the biological basis of identity. He believes it lies in the pattern of connections between the brain's neurons, which change slowly over time as we learn and grow. The connectome, as it's called, is where our genetic inheritance intersects with our life experience. It's where nature meets nurture. Seung introduces us to the dedicated researchers who are mapping the brain's connections, neuron by neuron, synapse by synapse.

It is a monumental undertaking #151; the scientific equivalent of climbing Mount Everest #151; but if they succeed, it could reveal the basis of personality, intelligence, memory, and perhaps even mental disorders. Many scientists speculate that people with anorexia, autism, and schizophrenia are #147; wired differently, #148; but nobody knows for sure. The brain's #146 wiring has never been seen clearly. In sparklingly clear prose, Seung reveals the amazing technological advances that will soon help us map connectomes. He also examines the evidence that these maps will someday allow humans to #147; upload #148; their minds into computers, achieving a kind of immortality. 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. Welcome to the future of neuroscience. – Distributed by Syndetic Solutions, Inc.

BOOK DESCRIPTION = We know that each of us is unique, but science has struggled to pinpoint where, precisely, our uniqueness resides. Is it in our genes? The structure of our brains? Our genome may determine our eye color and even aspects of our personality. But our friendships, failures, and passions also shape who we are. The question is: how?

Sebastian Seung, a dynamic professor at MIT, is on a quest to discover the biological basis of identity. He believes it lies in the pattern of connections between the brain's neurons, which change slowly over time as we learn and grow. The connectome, as it's called, is where our genetic inheritance intersects with our life experience. It's where nature meets nurture.

Seung introduces us to the dedicated researchers who are mapping the brain's connections, neuron by neuron, synapse by synapse. It is a monumental undertaking—the scientific equivalent of climbing Mount Everest—but if they succeed, it could reveal the basis of personality, intelligence, memory, and perhaps even mental disorders such as autism and schizophrenia. Many scientists speculate that people with anorexia, autism, and schizophrenia are "wired differently," but nobody knows for sure. The brain's wiring has never been clearly seen.

In sparklingly clear prose, Seung reveals the amazing technological advances that will soon help us map connectomes. He also examines the evidence that these maps will someday allow humans to "upload" their minds into computers, achieving a kind of immortality.

The book, Connectome, is a mind-bending adventure story that presents a daring scientific and technological vision for understanding what makes us who we are, both as individuals and as a species. Welcome to the future of neuroscience.

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[1] Seung has an intelligent, educated and powerful voice, with a flair for the well-placed metaphor. He argues 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.

[2] 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.

[3] 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.

[4] 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.

[5] 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.

[6] 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.

[7] 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. It is 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 the books, Who's in Charge?: Free Will and the Science of the Brain, Human: The Science Behind What Makes Us Unique, and The Ethical Brain.

[8] An amiable guide, witty and exceptionally clear in describing complex matters for the general reader...fascinating...beautifully explained and analyzed --- as I might have expected from Seung. -- This text refers to the Kindle Edition edition.

[9] 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. -- Abigail Zuger, M.D., New York Times

[10] Accessible, witty, imminently 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

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1] Note: Reviewed by "Book Fanatic" = This is a very good book with a very strange name. "Connectome" means the entire collection of our brain's neuronal connections, the totality of how we are wired together. The subtitle "How the Brain's Wiring Makes Us Who We Are" is a fairly accurate representation of what the book is about. I believe this is the author Sebastian Seung's first book and he demonstrates quite a talent for explaining complex topics to a general popular audience.

What I particularly like about this book was the material was not at all the usual popular neuroscience stuff. This book covered new ground for me and I think will for most other readers. Seung spends a decent amount of time in the beginning explaining some basics about neurons and how the brain works, but it is when you get into the central ideas of the book that it gets really interesting.

One thing I really liked about the book was how the author explained the technologies and challenges required to actually create a connectome of even simple brains much less a human. According to Seung we don't have computers powerful enough or the tools to even analyze a cubic millimeter of a bird brain's connectome, much less a complete human brain a million times that size.

The whole book was compelling and informative and I can easily recommend it to others. One thing to keep in mind however, is that it is very futuristic in a sense. Seung's ideas are very plausible to me but still unproven and speculative. The technology to validate them is not going to be available for many years.

[2] Note: Review by J. A. Bell = I loved this absorbing book about neuroscience that took me through the past, present and future of the human brain. Though I'm not a scientist, I easily understood the challenges, clearly laid down by Dr. Seung, of finding connectomes. His very eclectic approach made it that much more interesting, as he argued from "first principles," and questioned all of his beliefs.

Prior to reading the book, Connectome, I had never heard the term. It was originally coined by Olaf Sporns and his colleagues in a 2005 paper. "A connectome is the totality of connections between the neurons in a nervous system. ... It is all of the connections." (xiii) "You may have heard of the $30 million Human Connectome Project, which was announced in 2010 by the U.S. National Institutes of Health (NIH). Most people don't realize that this project is only about regional connectomes, and has nothing to do with neuronal connectomes." (181)

While Dr. Seung concedes that "in the immediate future, a regional connectome seems like the most useful kind for psychologists and neurologists" he is forward thinking to a day that all 100 billion neurons in the human brain are named, given a characteristic location and shape and are diagrammed. "To find connectomes, we will have to create machines that produce clear images of neurons and synapses over a large field of view." (140)

This is an ambitious goal. "We still don't know how many types [of neurons] there are, though we know the number is large. The brain is more like a tropical rainforest, which contains hundreds of species, than a coniferous forest with perhaps a single species of pine tree. One expert has estimated that there are thousands of neuron types in the cortex alone." (176) The connectome of a small roundworm (C. elegans) took seven years to "map" even though it has only 300 neurons scattered throughout its body. (xi) Seung imagines the human connectome could be completed by the end of this century thanks to rapid advances in technology for imaging the brain and slicing brain tissue, and high-speed computers to crunch the data.

This is all very fascinating and futuristic, but aside from connectome, this book is full of interesting information about intelligence, the effect of drugs on the brain, how the brain repairs itself after injury or stroke, as well as history and philosophy. For instance:

"Other animal species, such as lizards, are able to regenerate large parts of their nervous systems after injury. And human children regenerate better than adults do. In the 1970s, when physicians realized that children's fingertips regenerate like lizards' tails, they stopped attempting to reattach severed fingertips through surgery; now, they simply let the fingertips grow back. Hidden powers of regeneration might lie dormant in adults, and the new field of regenerative medicine seeks to awaken them." (221)

"Neurons continue to grow branches well after birth." This process is called the "wiring" of the brain, since axons and dendrites resemble wires. Axons have to grow the most, since they are much longer than dendrites. Imagine the tiny growing tip of an axon, known as a "growth cone" for its roughly conical shape. If a growth cone were blown up to human size, its travels would take it to the other side of a city. How is the growth cone able to navigate such long distances? Many neuroscientists study this phenomenon, and they've found that the growth cone acts like a dog sniffing its way home. The surfaces of neurons are coated with special guidance molecules that act like scents on the ground, and the interstitial spaces between neurons contain drifting guidance molecules that act like scents in the air. Growth cones are equipped with molecular sensors and can "smell" the guidance molecules to find their destination. "The production of guidance molecules and sensors for these molecules is under genetic control. That's how genes guide the wiring of the brain." (106)

For some inexplicable reason, I found the following most interesting: "The need for inhibition might be the chief reason why the brain relies so heavily on synapses that transmit chemical signals. There is actually another kind of synapse, one that directly transmits electrical signals without using neurotransmitters. Such electrical synapses work more quickly, since they eliminate time-consuming steps of converting signals from electrical to chemical and then back to electrical, but there are no inhibitory electrical synapses, only excitatory ones. Perhaps because of this and other limitations, electrical synapses are much less common than chemical ones." (56)

Any reader interested in preserving his or her brain in hopes of achieving immortality will want to read the chapter, "To Freeze or to Pickle?" Cryobiology is examined scientifically as well as from ethical and philosophical points of view.

"Worthwhile things that have never been done can only be done by means that have never yet existed," Sebastian Seung tells us in the book, mapping the 100+ billion neurons in the human brain is certainly one such project, and we are far from having the means to do so.

But already, with the mapping and study of the 300 neurons in the C.elegans roundworm and ongoing development in imaging technology (such as the automated ultramicrotome), we are making strides toward understanding the structure and function of diverse neurons, and how their interactive network operates.

[3] Note: Reviewed by Arthur Morrissette = "Overall, I thought this book was very interesting and is a great read for anyone with a significant interest in neuroscience."

Author Seung is a professor of neuroscience at MIT, and a leading researcher on neural networks and the still-theoretical connectome. The term connectome, first coined in 2005, refers to the totality of connections between neurons. The field of neuroscience involves learning how neurons are strengthened, weakened, weighted and eliminated and how they connect and reconnect, rewire, and regenerate.

The first half of his book begins with chapters about: 1) the structure and role of neurons; 2) connectomes and their interconnectivity; 3) how memories are impressed and stored; 4) and genes. The next sections cover the development of imaging technologies and the lifelong task of reading and interpreting the voluminous data acquired.

Unfortunately, at this point, Seung comes across less as a scientist and more as a science fiction writer as he resorts to speculation about cryonics (brain and body preservation), uploading brains into computers, and immortality. The book would be much more substantial if he omitted the last few chapters.

Seung, however, is a talented writer with the unique ability to impart scientific theory in understandable language. Obviously possessing a highly associative brain himself, he is skilled at explaining fundamentals of neuroscience through the frequent use of everyday analogies.

He compares the process of dendrites spiking to a weighted voting system influenced by favoritism. All votes must be in before dendrites know they can spike, he tells us, further explaining that some votes count more than others -some neurons and their synapses transport more important signals than others do, and therefore have greater impact.

"If the axons and dendrites in the gray matter are like local streets, the axons of the white matter are like superhighways of the brain," he writes.

In another chapter, he briefly takes us on a "fantastic voyage". "Perhaps you are a protein molecule sitting on a molecular motor car running on a molecular track. You are being transported on the long journey from your birthplace, the cell body, to your destination, the outer reaches of the axon... To find an entire connectome, though, you'd have to explore every passage in the brain's labyrinth."

I was especially pleased that he compared RAM and hard drive memory to short-term and long-term memory in the brain - a comparison I make in computer skills classes I teach.

But I wish that Seung introduced us to the brain as a whole before zeroing in on neurons, and that he provided a detailed, labeled map of the parts of the brain. He included a lot of rough illustrations and diagrams, but few quality photos.

I thought that his discussion of factors contributing to memory was incomplete - he didn't even mention the emotional intensity of a learning experience, multi-sensory involvement, and mindful attention and intention, all factors I found to be critical during graduate training in education and psychology, as well as my personal brain fitness "workouts".

My primary criticism of the book, however, is that Seung doesn't differentiate enough between proven facts, generally accepted theories, his own personal theories, and pure speculation.

Nevertheless, his often chatty and informal yet highly informative writing style is enjoyable. His numerous and sometimes humorous analogies help us envision neural activity, understand the intricacies of the connectome, and appreciate the immense accomplishments and challenges of neuroscience.

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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, such as: your parents’ divorce or 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."


Sebastian Seung


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