A Nobel Prize–winning neuroscientist’s probing investigation of what brain disorders can tell us about human nature
Eric R. Kandel, the winner of the Nobel Prize in Physiology or Medicine for his foundational research into memory storage in the brain, is one of the pioneers of modern brain science. His work continues to shape our understanding of how learning and memory work and to break down age-old barriers between the sciences and the arts.
In his seminal new book, The Disordered Mind, Kandel draws on a lifetime of pathbreaking research and the work of many other leading neuroscientists to take us on an unusual tour of the brain. He confronts one of the most difficult questions we face: How does our mind, our individual sense of self, emerge from the physical matter of the brain? The brain’s 86 billion neurons communicate with one another through very precise connections. But sometimes those connections are disrupted. The brain processes that give rise to our mind can become disordered, resulting in diseases such as autism, depression, schizophrenia, Parkinson’s, addiction, and post-traumatic stress disorder. While these disruptions bring great suffering, they can also reveal the mysteries of how the brain produces our most fundamental experiences and capabilitiesthe very nature of what it means to be human. Studies of autism illuminate the neurological foundations of our social instincts; research into depression offers important insights on emotions and the integrity of the self; and paradigm-shifting work on addiction has led to a new understanding of the relationship between pleasure and willpower.
By studying disruptions to typical brain functioning and exploring their potential treatments, we will deepen our understanding of thought, feeling, behavior, memory, and creativity. Only then can we grapple with the big question of how billions of neurons generate consciousness itself.
|Publisher:||Farrar, Straus and Giroux|
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About the Author
Eric R. Kandel is a University Professor and Fred Kavli Professor at Columbia University and a Senior Investigator at the Howard Hughes Medical Institute. The recipient of the 2000 Nobel Prize in Physiology or Medicine for his studies of learning and memory, he is the author of In Search of Memory, a memoir that won a Los Angeles Times Book Prize; The Age of Insight: The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present, which won the Bruno Kreisky Award in Literature, Austria’s highest literary award; and Reductionism in Art and Brain Science: Bridging the Two Cultures, a book about the New York School of abstract art. He is also the coauthor of Principles of Neural Science, the standard textbook in the field.
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WHAT BRAIN DISORDERS CAN TELL US ABOUT OURSELVES
The greatest challenge in all of science is to understand how the mysteries of human nature — as reflected in our individual experience of the world — arise from the physical matter of the brain. How do coded signals, sent out by billions of nerve cells in our brain, give rise to consciousness, love, language, and art? How does a fantastically complex web of connections give rise to our sense of identity, to a self that develops as we mature yet stays remarkably constant through our life experiences? These mysteries of the self have preoccupied philosophers for generations.
One approach to solving these mysteries is to reframe the question: What happens to our sense of self when the brain does not function properly, when it is beset by trauma or disease? The resulting fragmentation or loss of our sense of self has been described by physicians and lamented by poets. More recently, neuroscientists have studied how the self comes undone when the brain is under assault. A famous example is Phineas Gage, the nineteenth-century railway worker whose personality changed dramatically after an iron rod pierced the front of his brain. Those who had known him before his injury said simply, "Gage is no longer Gage."
This approach implies a "normal" set of behaviors, both for an individual and for people in general. The dividing line separating "normal" and "abnormal" has been drawn in different places by different societies throughout history. People with mental differences have sometimes been seen as "gifted" or "holy," but more frequently they have been treated as "deviant" or "possessed" and subjected to terrible cruelty and stigmatization. Modern psychiatry has attempted to describe and catalogue mental disorders, but the migration of various behaviors across the line separating the normal from the disordered is a testament to the fact that the boundary is indistinct and mutable.
All of these variations in behavior, from those considered normal to those considered abnormal, arise from individual variations in our brains. In fact, every activity we engage in, every feeling and thought that gives us our sense of individuality, emanates from our brain. When you taste a peach, make a difficult decision, feel melancholy, or experience a rush of joyous emotion when looking at a painting, you are relying entirely on the brain's biological machinery. Your brain makes you who you are.
You're probably confident that you experience the world as it is — that the peach you see, smell, and taste is exactly as you perceive it. You rely on your senses to give you accurate information so that your perceptions and actions are grounded in an objective reality. But that's only partly true. Your senses do provide the information you need to act, but they don't present your brain with an objective reality. Instead, they give your brain the information it needs to construct reality.
Each of our sensations emerges from a different system of the brain, and each system is fine-tuned to detect and interpret a particular aspect of the external world. Information from each of the senses is gathered by cells designed to pick up the faintest sound, the slightest touch or movement, and this information is carried along a dedicated pathway to a region of the brain that specializes in that particular sense. The brain then analyzes the sensations, engaging relevant emotions and memories of past experience to construct an internal representation of the outside world. This self-generated reality — in part unconscious, in part conscious — guides our thoughts and our behavior.
Ordinarily, our internal representation of the world overlaps to a great degree with everyone else's, because our neighbor's brain has evolved to work in the same way as our own; that is, the same neural circuits underlie the same mental processes in every person's brain. Take language, for example: the neural circuits responsible for expression of language are located in one area of the brain, while the circuits responsible for comprehension of language are located in another area. If during development those neural circuits fail to form normally, or if they are disrupted, our mental processes for language become disordered and we begin to experience the world differently from other people — and to act differently.
Disruptions of brain function can be both frightening and tragic, as anyone who has witnessed a grand mal seizure or seen the anguish of a deep depression can tell you. The effects of extreme mental illness can be devastating to individuals and their families, and the global suffering from these diseases is immeasurable. But some disruptions of typical brain circuitry can confer benefits and affirm a person's individuality. In fact, a surprising number of people who suffer from what one might see as a disorder would choose not to eradicate that aspect of themselves. Our sense of self can be so powerful and essential that we are reluctant to relinquish even those portions of it that cause us to suffer. Treatment of these conditions too often compromises the sense of self. Medications can deaden our will, our alertness, and our thought processes.
Brain disorders provide a window into the typical healthy brain. The more scientists and clinicians learn about brain disorders — from observing patients and from neuroscientific and genetic research — the more they understand about how the mind works when all brain circuits are functioning robustly, and the more likely they are to be able to develop effective treatments when some of those circuits fail. The more we learn about unusual minds, the more likely we are as individuals and as a society to understand and empathize with people who think differently and the less likely we are to stigmatize or reject them.
PIONEERS IN NEUROLOGY AND PSYCHIATRY
Until about 1800, only disorders that resulted from visible damage to the brain, as seen at autopsy, were considered medical disorders; these disorders were labeled neurological. Disorders of thought, feelings, and mood, as well as drug addiction, did not appear to be associated with detectable brain damage and, as a result, were considered to be defects in a person's moral character. Treatments for these "weak-minded" people were designed to "toughen them up" by isolating them in asylums, chaining them to the walls, and exposing them to deprivations or even torture. Not surprisingly, this approach was medically fruitless and psychologically destructive.
In 1790 the French physician Philippe Pinel formally founded the field we now call psychiatry. Pinel insisted that psychiatric disorders are not moral disturbances but medical diseases, and that psychiatry should be considered a subdiscipline of medicine. At Salpêtrière, Paris's large psychiatric hospital, Pinel freed the mental patients from their chains and introduced humane, psychology-oriented principles that were a forerunner of present-day psychotherapy.
Pinel argued that psychiatric disorders strike people who have a hereditary predisposition and who are exposed to excessive social or psychological stress. This view is remarkably close to the view of mental illness that we hold today.
Although Pinel's ideas had a great moral impact on the field of psychiatry by humanizing the treatment of patients, no further progress was made in understanding psychiatric disorders until the early twentieth century, when the great German psychiatrist Emil Kraepelin founded modern scientific psychiatry. Kraepelin's influence cannot be overstated, and I will weave his story through this book as it weaves through the history of neurology and psychiatry.
Kraepelin was a contemporary of Sigmund Freud, but whereas Freud believed that mental illnesses, although based in the brain, are acquired through experience — often a traumatic experience in early childhood — Kraepelin held a very different view. He thought that all mental illnesses have a biological origin, a genetic basis. As a result, he reasoned, psychiatric illnesses could be distinguished from one another much as other medical illnesses are: by observing their initial manifestations, their clinical courses over time, and their long-term outcomes. This belief led Kraepelin to establish a modern system for classifying mental illness, a system still in use today.
Kraepelin was inspired to take a biological view of mental illnesses by Pierre Paul Broca and Carl Wernicke, two physicians who first illustrated that we can gain remarkable insights into ourselves by studying disorders of the brain. Broca and Wernicke discovered that specific neurological disorders can be traced to specific regions of our brain. Theiradvances led to the realization that the mental functions underlying normal behavior can also be localized to specific regions and sets of regions of the brain, thus laying the groundwork for modern brain science.
In the early 1860s Broca noticed that one of his patients, a man named Leborgne, who suffered from syphilis, had a peculiar language deficit. Leborgne could understand language perfectly well, but he couldn't make himself understood. He could take in what someone told him, as evidenced by his ability to follow instructions to the letter, but when he tried to speak, only unintelligible mumbles came out. The man's vocal cords weren't paralyzed — he could easily hum a tune — but he could not express himself in words. Nor could he express himself through writing.
After Leborgne died, Broca examined his brain, looking for clues to his affliction. He found a region in the forward part of the left hemisphere that appeared blighted by disease or injury. Broca eventually encountered eight additional patients with the same difficulty producing language and found that they all had damage in the same area on the left side of the brain, a region that became known as Broca's area (fig. 1.1). These findings led him to conclude that our ability to speak resides in the left hemisphere of the brain, or as he put it, "We speak with the left hemisphere."
In 1875 Wernicke observed the mirror image of Leborgne's defect. He encountered a patient whose words flowed freely but who could not understand language. If Wernicke told him to "Put object A on top of object B," the man would have no idea what he was being asked to do. Wernicke tracked this deficit in language comprehension to damage in the back of the left hemisphere, a region that became known as Wernicke's area (fig. 1.1).
Wernicke had the great insight to realize that complex mental functions like language do not reside in a single region of the brain but instead involve multiple, interconnected brain regions. These circuits form the neural "wiring" of our brain. Wernicke demonstrated not only that comprehension and expression are processed separately but that they are connected to each other by a pathway known as the arcuate fasciculus. The information we obtain from reading is transmitted from our eyes to the visual cortex, and the information from hearing is sent from our ears to the auditory cortex. Information from these two cortical areas then converges in Wernicke's area, which translates it into a neural code for understanding language. Only then does the information proceed to Broca's area, enabling us to express ourselves (fig. 1.1).
Wernicke predicted that someday, someone would find a disorder of language that involves simply a disconnect between the two areas. This proved to be the case: people with damage to the arcuate pathway connecting the two areas can understand language and express language, but the two functions operate independently. This is a bit like a presidential press conference: information comes in, information goes out, but there is no logical connection between them.
Scientists now think that other complex cognitive skills also require the participation of several quite distinct but interconnected regions of the brain.
Although the circuitry for language has proved to be even more complex than Broca and Wernicke realized, their initial discoveries formed the basis of our modern view of the neurology of language and, by extension, our view of neurological disorders. Their emphasis on location, location, location resulted in major advances in the diagnosis and treatment of neurological disease. Moreover, the damage typically caused by neurological diseases is easily visible in the brain, making them far easier to identify than most psychiatric disorders, in which the damage is much subtler.
The search for localization of function in the brain was enhanced dramatically in the 1930s and '40s by Canada's renowned neurosurgeon Wilder Penfield, who operated on people suffering from epilepsy caused by scar tissue that had formed in the brain after a head injury. Penfield was seeking to elicit an aura, the sensation many epileptic patients experience before a seizure. If successful, he would have a good idea of which tiny bit of the brain to remove in order to relieve his patients' seizures without damaging other functions, such as language or the ability to move.
Penfield's patients were awake during the operation — the brain has no pain receptors — so they could tell him what they were experiencing when he stimulated various areas in their brain. Over the next several years, in the course of nearly four hundred operations, Penfield mapped the regions of our brain that are responsible for the sensations of touch, vision, and hearing and for the movements of specific parts of our body. His maps of sensory and motor function are still used today.
What was truly amazing was Penfield's discovery that when he stimulated the temporal lobe, the part of the brain that is just above the ear, his patient might suddenly say, "Something is coming back to me as if it is a memory. I hear sounds, songs, parts of symphonies." Or, "I hear the lullaby my mother used to sing to me." Penfield began to wonder if it were possible to locate a mental process as complex and mysterious as memory to specific regions in the physical brain. Eventually, he and others determined that it is.
NEURONS: THE BUILDING BLOCKS OF THE BRAIN
Broca's and Wernicke's discoveries revealed where in the brain certain mental functions are located, but they stopped short of explaining how the brain carries them out. They were unable to answer basic questions such as, What is the biological makeup of the brain? How does it function?
Biologists had already established that the body is composed of discrete cells, but the brain appeared to be different. When scientists looked through their microscopes at brain tissue, they saw a tangled mess that seemed to have no beginning and no end. For this reason, many scientists thought the nervous system was a single, continuous web of interconnected tissue. They weren't sure there was such a thing as a discrete nerve cell.
Then, in 1873, an Italian physician named Camillo Golgi made a discovery that would revolutionize scientists' understanding of the brain. He injected silver nitrate or potassium dichromate into brain tissue and observed that, for reasons we still don't understand, a tiny fraction of the cells took up the stain and turned a distinctive black color. Out of an impenetrable block of neural tissue, the fine and elegant structure of individual neurons was suddenly thrown into high relief (fig. 1.2).
The first scientist to take advantage of Golgi's discovery was a young Spaniard named Santiago Ramón y Cajal. In the late 1800s Cajal applied Golgi's stain to brain tissue from newborn animals. This was a wise move: early in development the brain has fewer neurons, and their shape is simpler, so they are easier to see and examine than neurons in a mature brain. Using Golgi's stain in the immature brain, Cajal could identify isolated cells and study them one at a time.
Cajal saw cells that resembled the sprawling canopies of ancient trees, others that ended in compact tufts, and still others that sent branches arcing into unseen regions of the brain — shapes that were completely different from the simple, well-defined shapes of other cells in the body. In spite of this startling diversity, Cajal determined that each neuron has the same four principal anatomical components (fig. 1.3): the cell body, the dendrites, the axon, and the presynaptic terminals, which end in what are now known as synapses. The main component of the neuron is the cell body, which contains the nucleus (the repository of the cell's genes) and the majority of the cytoplasm. The multiple, thin extensions from the cell body, which look like the slender branches of a tree, are the dendrites. Dendrites receive information from other nerve cells. The single thick extension from the cell body is the axon, which can be several feet long. The axon transmits information to other cells. At the end of the axon are the presynaptic terminals. These specialized structures form synapses with the dendrites of target cells and transmit information to them across a small gap known as the synaptic cleft. Target cells may be neighboring cells, cells in another region of the brain, or muscle cells at the periphery of the body.(Continues…)
Excerpted from "The Disordered Mind"
Copyright © 2018 Eric R. Kandel.
Excerpted by permission of Farrar, Straus and Giroux.
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Table of Contents
1. What Brain Disorders Can Tell Us About Ourselves
2. Our Intensely Social Nature: The Autism Spectrum
3. Emotions and the Integrity of the Self: Depression and Bipolar Disorder
4. The Ability to Think and to Make and Carry Out Decisions: Schizophrenia
5. Memory, the Storehouse of the Self: Dementia
6. Our Intrinsic Creative Capability: Brain Disorders and Art
7. Movement: Parkinson’s and Huntington’s Diseases
8. The Interplay of Conscious and Unconscious Emotion: Anxiety,
Post-Traumatic Stress, and Faulty Decision Making
9. The Pleasure Principle and Freedom of Choice: Addictions
10. Sexual Differentiation of the Brain and Gender Identity
11. Consciousness: The Great Remaining Mystery of the Brain