The Disordered Mind

by Eric R. Kandel

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  Table of Contents

  A Note About the Author

  Copyright Page

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  For Denise,

  My constant companion, my strongest critic, and my continuous source of inspiration

  The mind is like an iceberg, it floats with one-seventh of its bulk above water.

  —Sigmund Freud

  INTRODUCTION

  I have spent my entire career trying to understand the inner workings of the brain and the motivation for human behavior. Having escaped from Vienna as a young boy soon after Hitler occupied it, I was preoccupied with one of the great mysteries of human existence: How can one of the most advanced and cultured societies on earth turn its efforts so rapidly toward evil? How do individuals, when faced with a moral dilemma, make choices? Can the splintered self be healed through skilled human interaction? I became a psychiatrist in hopes of understanding and acting on these difficult problems.

  As I began to appreciate the elusiveness of the problems of the mind, however, I turned to questions that could be answered more definitively through scientific research. I focused on small collections of neurons in a very simple animal, and eventually discovered some of the fundamental processes underlying elementary forms of learning and memory. While I have enjoyed my work a great deal and it has been amply appreciated by others, I realize that my findings represent but a small advance in the quest to understand the most complex entity in the universe—the human mind.

  This pursuit has animated philosophers, poets, and physicians since the dawn of humankind. Engraved on the entrance of the Temple of Apollo at Delphi was the maxim “Know thyself.” Ever since Socrates and Plato first reflected on the nature of the human mind, serious thinkers of every generation have sought to understand the thoughts, feelings, behavior, memories, and creative powers that make us who we are. For earlier generations, this quest was restricted to the intellectual framework of philosophy, as embodied in the seventeenth-century French philosopher René Descartes’s pronouncement “I think, therefore I am.” Descartes’s guiding idea was that our mind is separate from, and functions independently of, our body.1

  One of the great steps forward in the modern era was the realization that Descartes had it backward: in actuality, “I am, therefore I think.” This reversal came about in the late twentieth century, when a school of philosophy that was concerned with mind, a school led importantly by people such as John Searle and Patricia Churchland, merged with cognitive psychology,2 the science of mind, and both then merged with neuroscience, the science of the brain. The result was a new, biological approach to mind. This unprecedented scientific study of mind is based on the principle that our mind is a set of processes carried out by the brain, an astonishingly complex computational device that constructs our perception of the external world, generates our inner experience, and controls our actions.

  The new biology of mind is the last step in the intellectual progression that began in 1859 with Darwin’s insights into the evolution of our bodily form. In his classic book On the Origin of Species, Darwin introduced the idea that we are not unique beings created by an all-powerful God, but instead are biological creatures that have evolved from simpler animal ancestors and share with them a combination of instinctual and learned behavior. Darwin elaborated on this idea in his 1872 book, The Expression of the Emotions in Man and Animals,3 in which he presented an even more radical and profound idea: that our mental processes evolved from animal ancestors in much the same way that our morphological features did. That is, our mind is not ethereal; it can be explained in physical terms.

  Brain scientists, myself included, soon realized that if simpler animals exhibit emotions similar to ours, such as fear and anxiety in response to threats of bodily harm or diminished social position, we should be able to study aspects of our own emotional states in those animals. It subsequently became clear from studies of animal models that, much as Darwin had predicted, even our cognitive processes, including primitive forms of consciousness, evolved from our animal ancestors.

  The fact that we share aspects of our mental processes with simpler animals and can therefore study the workings of the mind on an elementary level in those animals is fortunate, because the human brain is astonishingly complex. That complexity is most evident—and most mysterious—in our awareness of self.

  Self-awareness leads us to question who we are and why we exist. Our myriad creation mythologies—the stories each society tells about its origins—arose from this need to account for the universe and our place in it. Seeking answers to these existential questions is an important part of what defines us as human beings. And seeking answers to how the intricate interactions of brain cells give rise to consciousness, to our awareness of self, is the great remaining mystery in brain science.

  How does human nature arise from the physical matter of the brain? The brain can achieve consciousness of self and can perform its remarkably swift and accurate computational feats because its 86 billion nerve cells—its neurons—communicate with one another through very precise connections. During the course of my career, my colleagues and I have been able to show in a simple invertebrate marine animal, Aplysia, that these connections, known as synapses, can be altered by experience. This is what enables us to learn, to adapt to changes in our surroundings. But the connections among neurons can also be altered by injury or disease; moreover, some connections may fail to form normally during development, or even to form at all. Such cases result in disorders of the brain.

  Today, as never before, the study of brain disorders is giving us new insights into how our mind normally functions. What we are learning about autism, schizophrenia, depression, and Alzheimer’s disease, for example, can help us understand the neural circuits involved in social interactions, in thoughts, feelings, behavior, memory, and creativity just as surely as studies of those neural circuits can help us understand brain disorders. In a larger sense, much as the components of a computer reveal their true functions when they break down, so the functions of the brain’s neural circuits become dramatically clear when they falter or fail to form correctly.

  This book explores how the processes of the brain that give rise to our mind can become disordered, resulting in devastating diseases that haunt humankind: autism, depression, bipolar disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, and post-traumatic stress disorder. It explains how learning about these disordered processes is essential for improving our understanding of the normal workings of the brain, as well as for finding new treatments for the disorders. It also illustrates that we can enrich our understanding of how the brain works by examining normal variations in brain function, such as how the brain differentiates during development to determine our sex and our gender identity. Finally, the book shows how the biological approach to mind is beginning to unravel the mysteries of creativity and of consciousness. We see, in particular, remarkable instances of creativity in people with schizophrenia and bipolar disorder and find that their creativity arises from
the same connections between brain, mind, and behavior present in everyone. Modern studies of consciousness and its disorders suggest that consciousness is not a single, uniform function of the brain; instead, it is different states of mind in different contexts. Moreover, as earlier scientists discovered and as Sigmund Freud had emphasized, our conscious perceptions, thoughts, and actions are informed by unconscious mental processes.

  In a larger sense, the biological study of mind is more than a scientific inquiry holding great promise for expanding our understanding of the brain and devising new therapies for people who have disorders of the brain. Advances in the biology of mind offer the possibility of a new humanism, one that merges the sciences, which are concerned with the natural world, and the humanities, which are concerned with the meaning of human experience. This new scientific humanism, based in good part on biological insights into differences in brain function, will change fundamentally the way we view ourselves and one another. Each of us already feels unique, thanks to our consciousness of self, but we will actually have biological confirmation of our individuality. This, in turn, will lead to new insights into human nature and to a deeper understanding and appreciation of both our shared and our individual humanity.

  1

  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.

  Althou
gh 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. Their advances 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.