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MYSTERIES MINDMIND OF THEOF THE Mind-Body Connections Happiness Depression Dreams Consciousness Memory Violence NEW AND UPDATED EXPLORATIONS OF HOW WE THINK, HOW WE BEHAVE AND WHAT WE FEEL SPECIAL ISSUE SPECIAL ISSUE $4.95 MYSTERIES Copyright 1997 Scientific American, Inc. Mysteries of the Mind 3 Master detective Hercule Poirot,the hero of many an AgathaChristie novel, boasted re- peatedly about the power of “the little gray cells” in his head to solve the toughest mys- teries. For philosophers, writers and other thinkers, however, those little gray cells have been the greatest mystery of all. How do a couple of pounds of spongy, electrically ac- tive tissue give rise to a psychological essence? How do we emerge from the neural thicket? Empirical scientists may be relative new-comers to this investigation (unlike the philosophers, they’ve been on the case for only a few hundred years), but they have taken long strides forward in that short time. In this special issue of Scientific American, some of the lead- The Persistent Mystery of Our Selves ® Established 1845 F R O M T H E E D I T O R S Scientific American Mysteries of the Mind is published by the staff of Scien- tific American, with project manage- ment by: John Rennie, EDITOR IN CHIEF Michelle Press, MANAGING EDITOR David Pope, PROJECT EDITOR W. Wayt Gibbs, Kristin Leutwyler, STAFF WRITERS Art Edward Bell, ART DIRECTOR Lisa Burnett, PRODUCTION EDITOR Bridget Gerety, PHOTOGRAPHY EDITOR Copy Maria-Christina Keller, COPY CHIEF Molly K. Frances; Daniel C. 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Paul, DIRECTOR Scientific American, Inc. 415 Madison Avenue • New York, NY 10017-1111 (212) 754-0550 PRINTED IN U.S.A. To be conscious that we are perceiving or thinking is to be conscious of our own existence. —Aristotle I have a prodigious quantity of mind; it takes me as much as a week sometimes to make it up. —Mark Twain ing researchers in neuroscience and in psychology discuss how much is now known about the nature of consciousness, memory, emo- tions, creativity, dreams and other mental phenomena. Their answers suggest that some of these mysteries may be largely solved within our lifetimes—even if new ones are posed in the process. But treat these articles as you would any good detective story: don’t turn right to the end for the answers. Half the fun is in tracing the deductions. RO B ER TO O ST I The scene of the crime Memory is the cabinet of imagination, the treasury of reason, the registry of conscience, and the council chamber of thought. —St. Basil The whole machinery of our intelligence, our general ideas and laws, fixed and external objects, principles, persons, and gods, are so many symbolic, algebraic expressions. —George Santayana JOHN RENNIE, Editor in Chief editors@sciam.com Copyright 1997 Scientific American, Inc. Stress makes the body more vulner- able to some physical illnesses; im- mune responses can contribute to depression and fatigue. Even though the brain and the immune system differ in their functions and organi- zation, they are interlinked at a sub- tle biochemical level. This fact sug- gests that drugs traditionally used to treat neurological problems might help against inflammatory maladies, and vice versa. 4 8 The Mind-Body Interaction in Disease Esther M. Sternberg and Philip W. Gold 18 The Problem of Consciousness Francis Crick and Christof Koch Neuroscientists are on the trail of how the physical brain gives rise to the psychological experience of mind. The key may be synchronous firing among sets of related neurons, generating coherence and meaning out of brain activity. 68 Emotion, Memory and the Brain Joseph E. LeDoux Emotional memories—such as the strongly felt associations behind phobias—form in a way that by- passes the brain’s higher centers. This route ensures faster responses when danger looms. 76 The Neurobiology of Fear Ned H. Kalin Clues to excessive human anxi- ety can be found by studying fear in monkeys and other spe- cies. Their example may lead to the development of better thera- pies for frightened people. 30 The Puzzle of Conscious Experience David J. Chalmers Might consciousness be an irre- ducible feature in nature, as ba- sic as mass or electrical charge? Making that radical assumption, this philosopher claims, might be the only way for science to make sense of the subjective ex- perience of self. Scrutinizing the self Patterns of excitement An experience not soon forgotten Alarm in the rhesus monkey Integrated organs: the brain and the immune system Mysteries of the Mind Copyright 1997 Scientific American, Inc. Scientific American Mysteries of the Mind (ISSN 1048- 0943), Special Issue Volume 7, Number 1, 1997, pub- lished by Scientific American, Inc., 415 Madison Avenue, New York, N.Y. 10017-1111. Copyright © 1997 by Scien- tific American, Inc. All rights reserved. No part of this is- sue may be reproduced by any mechanical, photo- graphic or electronic process, or in the form of a phonographic recording, nor may it be stored in a re- trieval system, transmitted or otherwise copied for pub- lic or private use without written permission of the pub- lisher. To purchase additional quantities: 1 to 9 copies: U.S. $4.95 each plus $1.00 per copy for postage and handling (outside U.S. 3.00 P & H); 10 to 49 copies: $4.45 each, postpaid; 50 copies or more: $3.95 each, postpaid. Send payment to Scientific American, Dept. MM, 415 Madison Avenue, New York, N.Y. 10017-1111. Canadian BN No. 127387652RT; QST No. Q1015332537. Cover image by Matt Mahurin. 5 84 Phantom Limbs Ronald Melzack People who have lost an arm or leg sometimes still “feel” the missing part. Neurobiologists are be- ginning to understand more fully what creates this disturbing illusion. 92 Autism Uta Frith Autistic individuals seem lost in their own inner world. Their isolation stems from biological abnormalities that may in part interfere with the ability to imagine other people’s mental states. 102 Seeking the Criminal Element W. Wayt Gibbs, staff writer Identifying people with violent tendencies might be a great way to prevent crime. Or it could cause still greater injustice. 40 The Pursuit of Happiness David G. Myers and Ed Diener Psychology has historical- ly dwelled on the gloom- ier side of the human condition, but now joy is starting to get its share of attention. Surprisingly, people are more cheerful than one might suppose. 44 Manic-Depressive Illness and Creativity Kay Redfield Jamison Bouts of depression and manic energy are unusu- ally common among gift- ed artists, musicians and writers. The painful roller coaster of their emotions may deepen their creative appreciation of the ambi- guities of everyday life. 53 Depression’s Double Standard Kristin Leutwyler, staff writer Around the world, the rates of depression are twice as high among women as among men. The reason is unclear, but biological dif- ferences between the sexes may contribute to this psy- chological gender gap. 58 The Meaning of Dreams Jonathan Winson Strangely meaningful images and bizarre flights of fancy may all be part of the dream- ing brain’s efforts to review memories, evaluate recent ex- periences and plot new strat- egies for surviving challenges in the waking world. Ghosts that feel real Anguish of the autistic child The violent mind How do you feel today? The moods of genius Map of female sadness Jacob’s dream SPECIAL ISSUE/1997 46% 27% 4% 2% 1% 0% Copyright 1997 Scientific American, Inc. The Mind-Body Interaction in Disease8 Mysteries of the Mind The Authors ESTHER M. STERNBERG and PHILIP W. GOLD carry out their research on stress and immune systems at the National Institute of Mental Health, where Sternberg is chief of the section on neu- roendocrinology and behavior and Gold is chief of the clini- cal neuroendocrinology branch. Sternberg received her M.D. from McGill University. Her work on the mechanisms and molecular basis of neu- roimmune communication has led to a growing recognition of the importance of the mind- body interaction. She also is an authority on the L-trypto- phan eosinophilia myalgia syndrome, which reached al- most epidemic proportions in 1989. Prior to joining the NIMH in 1974, Gold received his medical training at Duke University and Harvard Uni- versity. Gold and his group were among the first to intro- duce data implicating cortico- tropin-releasing hormone and its related hormones in the pathophysiology of melan- cholic and atypical depression and in the mechanisms of ac- tion of antidepressant drugs. The Mind-Body Interaction in Disease The brain and immune system continuously signal each other, often along the same pathways, which may explain how state of mind influences health by Esther M. Sternberg and Philip W. Gold The belief that the mind plays an important role in physical illness goesback to the earliest days of medicine. From the time of the ancient Greeksto the beginning of the 20th century, it was generally accepted by bothphysician and patient that the mind can affect the course of illness, and it seemed natural to apply this concept in medical treatments of disease. After the dis- covery of antibiotics, a new assumption arose that treatment of infectious or inflam- matory disease requires only the elimination of the foreign organism or agent that triggers the illness. In the rush to discover new antibiotics and drugs that cure specific infections and diseases, the fact that the body’s own responses can influence suscepti- bility to disease and its course was largely ignored by medical researchers. It is ironic that research into infectious and inflammatory disease first led 20th-cen- tury medicine to reject the idea that the mind influences physical illness, and now re- search in the same field—including the work of our laboratory and of our collabora- tors at the National Institutes of Health—is proving the contrary. New molecular and pharmacological tools have made it possible for us to identify the intricate network that exists between the immune system and the brain, a network that allows the two systems to signal each other continuously and rapidly. Chemicals produced by im- mune cells signal the brain, and the brain in turn sends chemical signals to restrain the immune system. These same chemical signals also affect behavior and the response to stress. Disruption of this communication network in any way, whether inherited or through drugs, toxic substances or surgery, exacerbates the diseases that these systems guard against: infectious, inflammatory, autoimmune and associated mood disorders. The clinical significance of these findings is likely to prove profound. They hold the promise of extending the range of therapeutic treatments available for various dis- orders, as drugs previously known to work primarily for nervous system problems are shown to be effective against immune maladies, and vice versa. They also help to substantiate the popularly held impression (still discounted in some medical cir- cles) that our state of mind can influence how well we resist or recover from infec- tious or inflammatory diseases. The brain’s stress response system is activated in threatening situations. The im- mune system responds automatically to pathogens and foreign molecules. These two response systems are the body’s principal means for maintaining an internal steady state called homeostasis. A substantial proportion of human cellular machinery is dedicated to maintaining it. Immune response can be altered at the cellular level by stress hormones. Copyright 1997 Scientific American, Inc. The Mind-Body Interaction in Disease Mysteries of the Mind 9 RO B ER TO O ST I STRESS RESPONSE Nerves connect the brain to ev- ery organ and tissue. Challenging or threatening situations arouse the brain’s stress response, which involves the release of a hor- mone that stimulates physiologi- cal arousal and regulates the im- mune system. Key components in this stress response are the hy- pothalamus and locus ceruleus in the brain, the pituitary gland, the sympathetic nervous system and the adrenal glands. IMMUNE RESPONSE The immune system operates as a decentralized network, re- sponding automatically to any- thing that invades or disrupts the body. Immune cells generated in the bone marrow, lymph nodes, spleen and thymus communi- cate with one another using small proteins. These chemical messengers can also send signals to the brain, through either the bloodstream or nerve pathways such as the vagus nerve and nu- cleus of the tractus solitarius. HYPOTHALAMUS PITUITARY GLAND LOCUS CERULEUS BRAIN STEM LYMPH NODE SPLEEN ADRENAL GLAND THYMUS VAGUS NERVE BONE MARROW LIVER NUCLEUS OF TRACTUS SOLITARIUS KIDNEY Anatomy of the Stress and Immune Systems Copyright 1997 Scientific American, Inc. When homeostasis is disturbed or threatened, a repertoire of molecu- lar, cellular and behav- ioral responses comes into play. These respons- es attempt to counteract the disturbing forces in order to reestablish a steady state. They can be specific to the foreign invader or a particular stress, or they can be generalized and non- specific when the threat to homeostasis exceeds a certain threshold. The adaptive responses may themselves turn into stressors capable of pro- ducing disease. We are just beginning to under- stand the many ways in which the brain and the immune system are in- terdependent, how they help to regulate and counterregulate each oth- er and how they themselves can mal- function and produce disease. The stress response promotes physio- logical and behavioral changes that en- hance survival in threatening or taxing situations. For instance, when we are facing a potentially life-threatening sit- uation, the brain’s stress response goes into action to enhance our focused at- tention, our fear and our fight-or-flight response, while simultaneously inhibit- ing behaviors, such as feeding, sex and sleep, that might lessen the chance of immediate survival. The stress re- sponse, however, must be regulated to be neither excessive nor suboptimal; otherwise, disorders of arousal, thought and feeling emerge. The immune system’s job is to bar foreign pathogens from the body and to recognize and destroy those that penetrate its shield. The immune sys- tem also must neutralize potentially dangerous toxins, facilitate repair of damaged or worn tissues, and dispose of abnormal cells. Its responses are so powerful that they require constant reg- ulation to ensure that they are neither excessive nor indiscriminate and yet re- main effective. When the immune sys- tem escapes regulation, autoimmune and inflammatory diseases or immune deficiency syndromes result. The immune and central nervous sys- tems appear, at first glance, to be orga- nized in very different ways. The brain is usual- ly regarded as a central- ized command center, sending and receiving electrical signals along fixed pathways, much like a telephone net- work. In contrast, the im- mune system is decen- tralized, and its organs (spleen, lymph nodes, thy- mus and bone marrow) are located throughout the body. The classical view is that the immune system communicates by releasing immune cells in- to the bloodstream that float, like boats, to new locations to deliver their messages or to perform other functions. The central nervous and immune systems, however, are in fact more similar than differ- ent in their modes of re- ceiving, recognizing and integrating sig- nals from the external environment and in their structural design for accom- plishing these tasks. Both the central nervous system and the immune system possess “sensory” elements, which re- ceive information from the environ- ment and other parts of the body, and “motor” elements, which carry out an appropriate response. Cross Communication Both systems also rely on chemicalmediators for communication. Elec- trical signals along nerve pathways, for instance, are converted to chemical sig- nals at the synapses between neurons. The chemical messengers produced by immune cells communicate not only with other parts of the immune system but also with the brain and nerves, and chemicals released by nerve cells can act as signals to immune cells. Hormones from the body travel to the brain in the bloodstream, and the brain itself makes hormones. Indeed, the brain is perhaps the most prolific endocrine organ in the body and produces many hormones that act both on the brain and on tis- sues throughout the body. A key hormone shared by the central nervous and immune systems is cortico- tropin-releasing hormone (CRH); pro- duced in the hypothalamus and several other brain regions, it unites the stress and immune responses. The hypothala- mus releases CRH into a specialized bloodstream circuit that conveys the hormone to the pituitary gland, which is just beneath the brain. CRH causes the pituitary to release adrenocortico- tropin hormone (ACTH) into the bloodstream, which in turn stimulates the adrenal glands to produce cortisol, the best-known hormone of the stress response. Cortisol is a steroid hormone that in- creases the rate and strength of heart contractions, sensitizes blood vessels to the actions of norepinephrine (an adrenalinelike hormone) and affects many metabolic functions—actions that help to prepare the body to meet a stressful situation. In addition, cortisol is a potent immunoregulator and anti- inflammatory agent. It plays a crucial role in preventing the immune system from overreacting to injuries and dam- aging tissues. Furthermore, cortisol in- hibits the release of CRH by the hypo- thalamus—a simple feedback loop that keeps this component of the stress re- sponse under control. Thus, CRH and cortisol directly link the body’s brain- regulated stress response and its im- mune response. CRH-secreting neurons of the hypo- thalamus send fibers to regions in the brain stem that help to regulate the sympathetic nervous system, as well as to another brain stem area called the lo- cus