The Disordered Mind

by Eric R. Kandel

  Recently, three independent research groups have confirmed James’s theory.13 Using brain imaging, they discovered the anterior insular cortex, or insula, a little island in the cortex located between the parietal and temporal lobes. The insula is where our feelings are represented—our conscious awareness of the body’s response to emotionally charged stimuli. The insula not only evaluates and integrates the emotional or motivational importance of these stimuli, it also coordinates external sensory information and our internal motivational states. This consciousness of bodily states is a measure of our emotional awareness of self, the feeling that “I am.”

  Joseph LeDoux, a pioneer in the neurobiology of emotion whom we met in chapter 8, found that a stimulus takes one of two routes to the amygdala. The first is a rapid, direct pathway that processes unconscious sensory data and automatically links the sensory aspects of an event together. The second pathway sends information through several relays in the cerebral cortex, including the insula, and may contribute to the conscious processing of information. LeDoux argues that together, the direct and indirect pathways mediate both the immediate, unconscious response to a situation and the later, conscious elaboration of it.

  With these studies, we are now in a position to go beneath the surface of mental life and begin to examine how conscious and unconscious experiences are related. In fact, some of the most fascinating recent insights into consciousness have come from studies that parallel James’s thinking and examine consciousness through its role in other mental processes. Imaging studies by Elliott Wimmer and Daphna Shohamy, for instance, show that the same mechanisms in the hippocampus that are involved in the conscious recall of a memory can also guide and bias unconscious decisions.14

  Wimmer and Shohamy designed a study in which they first showed participants a series of paired images. The scientists then separated the images and, using the techniques of conditioned learning, presented some of the images to participants together with a monetary reward. Finally, they showed participants the images that had not been linked to a monetary reward and asked them which of the latter images they preferred. Participants tended to prefer images that had previously been paired with a rewarded image, even though the participants could not consciously recall the original pairs. The researchers concluded that the hippocampus can reactivate the association of the current image with its original mate and, working with the striatum, connect it to the memory of the reward, thus biasing a participant’s choice.

  Following on the realization that biology is involved in decision making and choice, Newsome and other neuroscientists began applying such economic models on the cellular level in animals in an effort to understand the rules that govern decision making. Meanwhile, economists began to incorporate the outcomes of those studies into their theories of economics.

  Neuroscientists have made good progress in studies of decision making by examining single nerve cells in primates. A key finding, epitomized by the work of Michael Shadlen, is that neurons in the association areas of the cortex, which are involved in decision making, have very different response properties than neurons in the sensory areas of the cortex. Sensory neurons respond to a current stimulus, whereas association neurons are active longer, presumably because they are part of the mechanism that links perception with a provisional plan for action.15

  Shadlen’s results indicate that association neurons accurately track the probabilities related to making a choice. For example, as a monkey sees more and more evidence indicating that a rightward target will dispense a reward, the neural activity that favors a rightward choice increases. This allows the monkey to accumulate evidence and make a choice when the probability of being correct passes some threshold, say 90 percent. The neurons’ activity and the decision they drive can occur very rapidly—often in less than a second. Thus, under the right circumstances, even rapid decisions can be made in nearly optimal fashion. This may explain why the fast, unconscious, System 1 mode of thinking has survived: it may be prone to error under some circumstances, but it is highly adaptive under others.

  PSYCHOANALYSIS AND THE NEW BIOLOGY OF MIND

  During the first half of the twentieth century, psychoanalysis provided remarkable new insights into unconscious mental processes, psychic determinism, infantile sexuality, and, perhaps most important of all, the irrationality of human motivation. Its approach was so novel and so powerful that for many years not only Freud but other intelligent and creative psychoanalysts as well could argue that psychotherapeutic encounters between patient and analyst provided the best context for scientific inquiry into the human mind.

  But the achievements of psychoanalysis during the second half of the century were less impressive. Although psychoanalytic thinking continued to progress, there were relatively few brilliant new insights. Most important, and most disappointing, psychoanalysis did not evolve scientifically. Specifically, it did not develop objective methods for testing the exciting ideas it had formulated. As a result, psychoanalysis entered the twenty-first century with its influence in decline.

  What led to this regrettable decline? First, psychoanalysis had exhausted much of its investigative power. Freud listened carefully to patients, and he listened in new ways. He also presented a provisional schema for making sense out of their apparently unrelated and incoherent associations. Today, however, little that is new in the way of theory remains to be learned merely by listening carefully to individual patients. Moreover, clinical observation of individual patients, in a context as susceptible to observer bias as the psychoanalytic relationship, is not a sufficient basis for a science of mind.

  Second, although psychoanalysis often thought of itself as a scientific discipline, it has rarely used scientific methods, and it has failed over the years to submit its assumptions to testable experimentation. Indeed, psychoanalysis has traditionally been far better at generating ideas than at testing them. In part that is because, with rare exceptions, the data gathered in psychoanalytic sessions are private: the patient’s comments, associations, silences, postures, movements, and other behaviors are privileged. In fact, privacy is central to establishing the trust needed in a psychoanalytic situation. As a result, we usually have only the analysts’ subjective accounts of what they believe happened in sessions. Such accounts are not comparable to scientific data.

  Third, with some notable exceptions, psychoanalysts have not embraced the last fifty years’ worth of knowledge about the biology of the brain and its control of behavior.

  If psychoanalysis is to regain its intellectual power and influence, as it should, it will need to engage constructively with the new biology of mind. Conceptually, the new biology could provide psychoanalysis with a scientific foundation for future growth. Experimentally, biological insights could serve as a stimulus for research, for testing specific ideas about how brain processes mediate mental processes and behavior. Imaging studies have provided evidence that psychoanalysis, as well as other forms of psychotherapy, is a biological treatment—it actually produces detectable, lasting physical changes in the brain and in behavior. Now we need to find out how.

  Fortunately, some people in the psychoanalytic community realized that empirical research was essential to the future of the discipline. Because of them, two trends have gained momentum in the last several decades. The first is the effort mentioned above, to align psychoanalysis with the new biology of mind. The second is the insistence on evidence-based psychotherapy, which we considered in chapter 3. Since almost every mental function requires the interplay of conscious and unconscious processes, the new biology of mind can provide a valuable link between psychoanalytic theory and modern cognitive neuroscience. Such a link would enable cognitive neuroscience to explore, modify, and, where appropriate, disprove psychoanalytic theories about the unconscious. It would also enable psychoanalytic ideas to enrich cognitive neuroscience.

  Using Dehaene’s operational approach, we might explore, for example, how Freud’s instinctual unconscious maps onto moder
n biological insights into social behavior and aggression. Do these unconscious processes reach the cerebral cortex, even though they may not reach consciousness? What neural systems govern mechanisms of defense, such as sublimation, repression, and distortion?

  Twenty-first-century biology is already in a good position to answer some of our questions about the nature of conscious and unconscious mental processes, but those answers will be richer and more meaningful if they are reached through a synthesis of the new biology of mind and psychoanalysis. This synthesis would add greatly to our knowledge of mental disorders and thus to our understanding of the neural circuitry of healthy brain function. New insights into healthy brain function would put us in a better position to understand people with brain disorders and to develop effective treatments for them.

  LOOKING AHEAD

  Consciousness remains a mystery. We know that it is not static, that states of consciousness vary. Moreover, consciousness entails making unconscious perceptual information available to wide areas of the cerebral cortex, especially the prefrontal cortex, the part of the brain responsible for integrating perception, memory, and cognition. Determining the nature of consciousness—in essence, how we acquire our awareness of self from unconscious activity in the brain—is one of the greatest scientific challenges of the twenty-first century, so answers will not come quickly or easily.

  While brain disorders can create disturbances in many aspects of our conscious experience—cognition, memory, mood, social interaction, volition, behavior—most of what we have learned about consciousness from these disorders thus far applies to the interaction of conscious and unconscious processes. That interplay is likely to be critical to our eventual understanding of how consciousness arises.

  CONCLUSION: COMING FULL CIRCLE

  We have learned more about the brain and its disorders in the past century than we have during all of the previous years of human history combined. Decoding the human genome has shown us how genes dictate the organization of the brain and how changes in genes influence disorders. We have new insights into the molecular pathways that underlie specific brain functions, such as memory, as well as the defective genes that contribute to disorders of those functions, such as Alzheimer’s disease. We also know more about the powerful interaction of genes and the environment in causing brain disorders, such as the role of stress in mood disorders and PTSD.

  Equally remarkable are recent breakthroughs in brain-scanning technology. Scientists can now track particular mental processes and mental disorders to specific regions and combinations of regions in the brain while a person is alert, with active nerve cells lighting up to create brightly colored maps of brain function. Finally, animal models of disorders have pointed us toward new avenues of research in human patients.

  As we have seen, brain disorders result when some part of the brain’s circuitry—the network of neurons and the synapses they form—is overactive, inactive, or unable to communicate effectively. The dysfunction may stem from injury, changes in synaptic connections, or faulty wiring of the brain during development. Depending on what regions of the brain they affect, disorders change the way we experience life—our emotion, cognition, memory, social interaction, creativity, freedom of choice, movement, or, most often, a combination of these aspects of our nature.

  Thanks in large part to advances in genetics, brain imaging, and animal models, scientists studying brain disorders have confirmed several general principles of how our brain normally functions. For example, imaging studies show that the left and right hemispheres of the brain deal with different aspects of mental functions and that the two hemispheres inhibit each other. Specifically, damage to the left hemisphere can free up the creative capabilities of the right hemisphere. More generally, when one neural circuit in the brain is turned off, another circuit, which was inhibited by the inactivated circuit, may turn on.

  Scientists have also uncovered some surprising links between disorders that appear to be unrelated because they are characterized by dramatically different kinds of behavior. Several disorders of movement and of memory, such as Parkinson’s disease and Alzheimer’s disease, result from misfolded proteins. The symptoms of these disorders vary widely because the particular proteins affected and the functions for which they are responsible differ. Similarly, both autism and schizophrenia involve synaptic pruning, the removal of excess dendrites on neurons. In autism, not enough dendrites are pruned, whereas in schizophrenia too many are. In another example, three different disorders—autism, schizophrenia, and bipolar disorder—share genetic variants. That is, some of the same genes that create a risk for schizophrenia also create a risk for bipolar disorder, and some of the same genes that create a risk for schizophrenia also create a risk for autism spectrum disorders.

  The interplay of unconscious and conscious mental processes is critical to how we function in the world. We see this particularly clearly in creativity and decision making. Our innate creativity—in any field—hinges on loosening the bonds of consciousness and gaining access to our unconscious. This is easier for some people than for others. Prinzhorn’s schizophrenic artists, with their diminished inhibitions and social constraints, had free access to their unconscious conflicts and desires, whereas the Surrealist artists had to devise ways of tapping into theirs. Decision making is different. Here, we are not aware of our unconscious emotions—or of the need for them. Yet studies have shown that people with damage to regions of the brain involving emotion have great difficulty making decisions.

  This new biology of mind has revolutionized our ability to understand the brain and its disorders. But how is the synthesis of modern cognitive psychology and neuroscience likely to affect our lives in the future?

  The new biology of mind will lead to radical changes in the way medicine is practiced, in two ways. First, neurology and psychiatry will merge into a common clinical discipline that focuses increasingly on the patient as an individual with particular genetic predispositions to health and disease. This focus will move us toward a biologically inspired, personalized medicine. Second, we will have, for the first time, a meaningful and nuanced biology of the processes in the brain that go awry in brain disorders, as well as the processes that lead to the sexual differentiation of our brain and our gender identity.

  It is likely that personalized medicine, with its focus on clinical DNA testing—the search for small genetic differences in individuals—will reveal who is at risk of developing a particular disease and thus enable us to modify the course of that disease through diet, surgery, exercise, or drugs many years before signs and symptoms appear. Currently, for example, newborn babies are screened primarily for treatable genetic diseases, such as phenylketonuria. Perhaps in the not-too-distant future, children at high risk for schizophrenia, depression, or multiple sclerosis will be identified and treated to prevent changes that would otherwise occur later in life. Similarly, middle-aged and older people may benefit from a determination of their individual risk profile for late-onset diseases such as Alzheimer’s or Parkinson’s. Indeed, DNA testing should also allow us to predict individual responses to drugs, including any side effects they may cause, leading to drugs tailored to the needs of individual patients.

  My own work has shown that learning—experience—changes the connections between neurons in the brain. This means that each person’s brain is slightly different from the brain of every other person. Even identical twins, with their identical genomes, have slightly different brains because they have been exposed to different experiences. It is very likely that, in the course of illuminating brain function, brain imaging will establish a biological foundation for the individuality of our mental life. If it does, we will have a powerful new way of diagnosing brain disorders and evaluating the outcome of various treatments, including different forms of psychotherapy.

  Seen in this light, understanding the biology of brain disorders is part of the continuous attempt of each generation of scholars to understand human thought and human a
ction in new terms. It is an endeavor that moves us toward a new humanism, one that draws on knowledge of our biological individuality to enrich our experience of the world and our understanding of one another.

  NOTES

  For a general introduction to the biology of the brain, see Eric R. Kandel et al., eds., Principles of Neural Science, 5th ed. (New York: McGraw Hill, 2013).

  INTRODUCTION

    1.  René Descartes, The Philosophical Writing of Descartes, trans. John Cottingham, Robert Stoothoff, and Dugald Murdoch, vol. 1 (Cambridge, U.K., and New York: Cambridge University Press, 1985).

    2.  John R. Searle, The Mystery of Consciousness (New York: The New York Review of Books, 1997).

    3.  Charles R. Darwin, The Expression of the Emotions in Man and Animals (London: John Murray, 1872).

  1. WHAT BRAIN DISORDERS CAN TELL US ABOUT OURSELVES

    1.  Eric R. Kandel and A. J. Hudspeth, “The Brain and Behavior,” in Kandel et al., Principles of Neural Science, 5th ed., 5–20.

    2.  William M. Landau et al., “The Local Circulation of the Living Brain: Values in the Unanesthetized and Anesthetized Cat,” Transactions of the American Neurological Association 80 (1955): 125–29.

    3.  Louis Sokoloff, “Relation between Physiological Function and Energy Metabolism in the Central Nervous System,” Journal of Neurochemistry 29 (1977): 13–26.

  2. OUR INTENSELY SOCIAL NATURE: THE AUTISM SPECTRUM

  For a general discussion on autism, see Uta Frith et al., “Autism and Other Developmental Disorders Affecting Cognition,” in Kandel et al., Principles of Neural Science, 1425–40.

    1.  David Premack and Guy Woodruff, “Does the Chimpanzee Have a Theory of Mind?” Behavioral and Brain Sciences 1, no. 4 (1978): 515–26.