Interview with a Brain Science Mastermind

FOR ALL THAT HUMANS KNOW about how the body works, the brain has eluded us the longest. We define our species as the thinking animal. We live in our heads. As Rene Descartes, so succinctly put it, we think, therefore we are. Yet, hidden from view, the living, working brain that lets us do all that thinking has kept most of its wisdom to itself.

But Michael Gazzaniga '61 is gaining on the brain. Not content with the limitations of traditional psychology or neurology, in 1980 he and a like-minded colleague, George Miller, co-founded a new academic field: cognitive neuroscience, the study of "how the brain enables mind." They established the Cognitive Science Institute, and Gazzaniga launched th & Journal of CognitiveNeuroscience to serve it. The field caught on. Today thousands of researchers count themselves as cognitive neuroscientists.

Gazzaniga was still a zoology major at Dartmouth when he found his life's work. He spent the summer of 1960 in the Caltech lab of neuroscientist Roger Sperry, who was studying "split-brain" cats, monkeys, and fish. "There is an axiom in biological circles stating that if you want to understand how something works, you study it functioning in disrepair," Gazzaniga says. To study how the brain hemispheres interact, Sperry was disconnecting them by severing the corpus callosum, a bundle of nerve fibers that runs between them. Hooked, Gazzaniga finished his Dartmouth studies, farewelled his Alpha Delta brothers ("I was 'Giraffe' in 'Animal House,''' he has confessed at professional meetings), and rushed back to Caltech for graduate research.

Gazzaniga soon became the first researcher to formally study split-brain humans: epileptics who'd had their corpus callosums severed in order to control seizures. Among his subjects was a group of patients who had been operated on by Dartmouth Medical School's Dr. Donald Wilson. Developing several cognitive tests to probe the workings of split brains, Gazzaniga found that the brain hemispheres, specialized and complex, have minds of their own. Nearly 40 years after the first research into the subject, Gazzaniga is still coaxing secrets from split brains.

He has also been inspiring some of the best brains in the cognitive neuroscience business. As visiting neuroscientist Michael Posner said in a recent lecture at Dartmouth, "Anything that Michael says, you tend to think about a while and then you do it." In 1989 Gazzaniga founded the country's first cognitive neuroscience degree-granting program—at the Dartmouth Medical School. In 1992 he established the world-class Center for Neuroscience at the University of California at Davis. In 1996 he returned to Dartmouth to develop a new cognitive neuroscience program that unites 30 researchers in the undergraduate College and the medical school, trains graduate students, and teaches undergraduates. The program just moved to its new headquarters, Moore Hall, which it shares with the recently renamed Department of Psychological and Brain Sciences. The space houses a new magnetic resonance imaging lab, and the program will be establishing a national database of MR images of the brain.

It doesn't take a brain surgeon (though he works with those, too) to see that Gazzaniga is a mastermind of cognitive neuroscience. He is constantly pushing new collaborations, organizing conferences, writing books (he's working on his eighth), moving the field forward. He recently sat down with DAM to speak his mind.

DAN: You and George Miller coined the term cognitive neuroscience in 1980. What does it mean?

MSG: Cognitive neuroscience means the science of the mind of how the brain enables mind. Some of the greatest neurologists, physiologists, and experimental psychologists provided the groundwork for this new field. A new term was needed because "pyschology" has been hijacked by clinicians, therapists, and others so much that it no longer describes the study of how the brain and mind do their jobs. Ultimately, anyone interested in the properties and mechanisms of human mental life will be drawn to cognitive neuroscience

DAM: Linguistics and artificial intelligence are part of cognitive neuroscience. Why?

MSG: Linguistics encompasses a major mental activity, the mechanisms of human language. So understanding the biological properties of language and how it develops in the brain—how it is represented—is a major endeavor. Some cognitive neuroscientists study the neural architecture of language and other perceptual and cognitive functions through computer models. Constructing a model of how any system works indeed a system as complex as natural language compelled us to recognize the advances and the limitations of artificial intelligence.

DAM: How can scientists get at how the brain produces the mind?

MSG: Carefully! There are many approaches used today. Animal models play a crucial role; direct recording from primate brains has been an important methodological tool. Studying the thought processes of primates by examining their neural firing patterns daring specific tasks has been extremely fruitful. Brain imaging methodologies, including functional magnetic resonance imaging (fMRI) are opening the human brain to us as never before. Cognitive neuroscience also continues to utilize the tried-and-true method of studying patients with focal brain lesions by carefully analyzing responses to perceptual and cognitive tests of all kinds. DAM: You were one of the first to study the cognitive functioning of split-brain patients. What does the split brain reveal about the way the normal brain functions?

MSG: Over the past 38 years studies of split-brain patients have generated dozens of insights—most very technical into how the human brain is structurally organized. We now know that the brain has a modular organization. Neuroscientists keep discovering areas in the brain that seem devoted to this or that particular function. For example, in vision there are areas associated with color perception, others for form perception, while still others are specialized for the detection of motion. These modules are somehow distributed in different physical places in the brain. Through understanding how each separated hemisphere functions, we can see how lateralized functions behave and how each contributes to our entire pattern of cognitive activity.

DAM: What has the split brain revealed about language?

MSG: The left brain has long been known to be dominant for language. But one of the first striking split-brain findings 30 years ago was that the right hemisphere also possesses some language skills. We found that the right brain can process some aspects of language, such as word-picture matching. It can spell, rhyme, judge categories, and many other things. And in some cases, it can even speak.

The first three cases we studied in the 1960s suggested that right-hemisphere language was a common event. Over the years we realized that it really isn't common, which is in keeping with other neurologic data, such as the effect of lateralized stroke on language processes. When right-brain language does occur, it is not clear why. Could it be due to brain damage resulting from epilepsy? Or does the brain's plasticity its capacity to change exceed our expectations? Some of our patients evinced right-hemisphere language early after surgery, evidence of a remarkable ability of the brain to learn and change. And in one patient, Case J.W., the capacity to speak out of the right hemisphere appeared 13 years after surgery! The patient can now.speak about information presented to both the left and the right brain an indication that there is functional plasticity well beyond any we had imagined for older brains.

DAM: Why is the brain lateralized?

MSG: We are just beginning to understand that. As we evolved there must have been fierce competition for cortical space. Since our two brains are richly interconnected by the corpus callosum, mutations could begin to change a part of the brain on one side and leave the other side free to continue providing the organism with the existing function. In this way, the overall cortex need not expand and yet new functions could arise in the human brain. Here at Dartmouth Paul Corballis, Margaret Funnell, and I are studying the implications for this type of cortical specialization. They are investigating the idea that as each hemisphere becomes specialized for a certain function, cortex that was previously devoted to other functions is co-opted for the new one. There is no apparent cost to the organism, though, since the other hemisphere has retained the function lost by the newly specialized hemisphere. In an intact brain, the functional losses caused by specialization are masked by the connections of the corpus callosum. Studies of split-brain patients, however, can reveal hemispheric deficits that result from specialization.

DAM: People often refer to being leftbrained or right-brained. Are people really left- or right-brainers?

MSG: Popular characterizatons of left-and right-brain abililities got out of hand, giving rise to the mistaken notion that people are either right- or left-brained. Some scientists oversimplified the ideas, and clever journalists further enhanced them. Cartoonists had a field day with it all.

The sort of functions a disconnected right or left hemisphere can or cannot do is one thing. The left is dominant for language and complex thought. The right is better at some perceptual tasks. But the normal person has these two hemispheres connected, so there is a seamless presence of these skills for all information presented to the brain.

That is not to say, of course, some people are not more verbal than others or more artistic than others. There is surely great variation in these skills. But to pin these differences onto a left- and right-brain anatomy is too simple.

DAM: You have proposed that there is an "interpreter" in the left brain. What is it?

MSG: The left hemisphere has a specialized system that we have designated the "interpreter," which seeks explanations

for why events occur. The right hemisphere does not appear to have one. Almost 20 years ago Joseph Le Doux and I carried out the experiment that revealed the interpreter. We asked the simple question, "How does the left hemisphere handle behaviors produced by the silent right brain?" We set up a simple test. Each hemisphere was presented with a separate picture, and each picture was related to one of four pictures placed in front of the subject (see illustration, page 27). The left and the right hemisphere easily picked the card that was correct for it by the left hand's pointing to the right hemisphere's choice and the right hand's pointing to the left hemisphere's choice. We then asked the left, speaking, hemisphere why the left hand was pointing to the object it had singled out. We knew that it really didn't know, since the decision to point to the card was made in the disconnected right hemisphere. But quick as a flash, it gave an explanation.

The advantage of having such a system is obvious. By going beyond observing contiguous events and asking why they happened, a brain can cope with these same events better, should they happen again.

DAM: Is the interpreter a physical entity or some sort of capacity?

MSG: Neuroscientists understand very little about how the brain does anything. If we truly understood how someone picks up a pencil, it would represent a major advance. If we truly understood how we see a face as opposed to a dishrag it would be a very big deal. The field has lots of ideas; lots of fascinating work is going on that attempts to nail down the specific mechanisms of these mental activites. But true understanding at this point is less than perfect.

When trying to understand how the brain represents a function like the intepreter we are truly at sea. We know which half of the brain it is in. We know if it is working or not. But we do not know its physical instantiation. We assume it is a discrete circuit of some kind, located somewhere in the left hemisphere, but that is all.

DAM: Is the interpreter unique to humans?

MSG: The interpreter certainly appears to be particular to humans. Usually it works with great success to tell us what is going on around us.

The left hemisphere's capacity for continual interpretation suggests it is always looking for order and reason, even where there is none. Nowhere has this been more dramatically realized than in a recent study we carried out with Professor George Wolford and Dartmouth's Center for Cognitive Neuroscience's first graduate, Michael Miller 'G98. In a simple test that requires one to guess if alight is going to appear on the top or bottom of a computer screen, we humans perform in an inventive way. In the experiment the stimulus appears on the top 80 percent of the time, but with a random sequence. While it quickly becomes evident that the top button is being illuminated more often, we keep trying to figure out a pattern and deeply believe we can. Yet by adopting this strategy we are rewarded only 68 percent of the time because the sequence is random.

If we simply always pressed the top button, we would be rewarded 80 percent of the time. Rats and other animals are more likely to "learn to maximize" and press only the top button. It turns out that the right hemisphere behaves in the same way. It does not try to interpret its experience and find the deeper meaning. It continues to live only in the moment. And the left, when asked to explain why it is attempting to figure out a pattern, always comes up with a theory even though it is spurious.

DAM: People make mistakes all the time. Is that the fault of the interpreter?

MSG: All the interpreter can do is build a story on the information it receives. If some process gives it false information, it will build up a false story. This happens to all of us all the time. As we try to remember a past event, we might misremember the time when something happened or the place where something happened. As we tell the story we incorporate that bad information into it, and as a result we make a mistake.

DAM: Can the interpreter create false memories?

MSG: Yes. As a matter of fact, we have used several paradigms to induce false memories in die laboratory. As it turns out, people normally do not explicitly encode the details of an event, yet later they will vividly remember details of the event based on what they expect to be there, or their schema of the event. For example, if you show somebody a picture of a beach scene they will notice general characteristics of the picture as well as objects that are novel or stand out. But items that were not in the picture but are consistent with the schema of a beach scene, for example a beach ball, people will vividly recollect having seen. It's as if the interpreter fills in the gaps of our memory. We have discovered in split-brain patients that this happens much more frequently in the left hemisphere than the right, probably due to the presence of the interpreter.

DAN: Humans define themselves as conscious beings. But it sounds like our brains are doing a lot of thinking we're not aware of.

MSG: If you think about it for a minute, you realize that the vast majority of our mental activities go on outside of our conscious awareness. When we throw a baseball we are not at all aware of the complex motor programs that go into the planning and execution of the act. As we construct a sentence, we are not aware of the processes that lead up to the arrangment of the phonological elements of a word. Indeed, when we solve basic math problems, we are not aware of how the answer came to us. Thus any theory of how the brain enables mind will have a large component that must describe the unconscious mind.

We are also only just beginning to understand how the many discrete and separate processing activities of the brain bind together to create the illusion that each of us is an integrated whole person with a coherent personal narrative.

DAM: Will greater knowledge of the biology of the mind force us to reshape traditional ideas about human behavior? For example, if impulsivity is beyond conscious control for some individuals, will our standards of culpability have to be re-examined?

MSG: There is no question that the mind sciences stand at the center of such issues. Establishing the degree and extent of culpability of a felon, for example, will be a legal process that will call upon the insights of cognitive neuroscience more and more. The deep biologic nature of most mental disease has finally been recognized and we have liberated ourselves from the deadening psychoanalytical theories of the past. Neurochemical aides have been created that can bring people with mental distress back to the normal range. This is certainly the case for diseases like depresssion, anxiety, schizophrenia, obsessive-compulsive disorders, and others. Impulsivity reflects a particular brain state and you can see how it could be argued that the brain state hijacked the mind into actions it normally would not have taken. This is a complex issue, but brain science will be involved in sorting out how to deal with it.

DAM: Is cognitive neuroscience revealing the brain to be more complicated than previously thought?

MSG: I don't think any serious student of the brain ever thought it was not hugely complicated. Take a look under the microscope at any slab of brain of any animal and you will stagger away from the microscope shaking your head. In the human brain there are 13 billion neurons with trillions of synaptic interactions. It defines complexity. Ironically, even though each of us possesses this huge computational machine, most of the time we use our brains for rather routine and mundane decisions.

DAM: What, then, is such brain complexity for?

MSG: The fundamental question for any evolutionary biologist is to first ask what an organ is for. To understand the kidney you need to know what its function is for the body; So, too, for the brain. The brain is a decision-making device. It is there to decide actions ones that will enhance the probability of achieving reproductive success. An organ that does that can also achieve any of a number of other tilings. As human beings, these are some of the things we most cherish. They are side shows so far as evolution goes. But they take on their own life and are usually the things that help us to create culture, which, needless to say, is a vastly important enterprise.

DAM: What more do you want to know about the brain?

MSG: The complexities of the brain are deep and almost endless. Every year 26,000 brain scientists go to a single meeting to report on their findings. Yet we are not even close to grasping the big issues of how the brain enables mind. Thus, how does one proceed? You go to work every day looking for the clue in your research that enlightens these profound issues. You can't predict where it will come from. As someone once said, the wonderful thing about a new idea is that we don't know about it yet.

Karen Endicott is senior editor of this magazine.

fig. 1

Michael S. Gazzaniga

the corpus callosum

When each hemisphere of a split-brain patient is shown aproblem and has to choose an answer, the left brain theonly one that can speak tries to explain the left hand'schoice. But the left brain doesn't really know why the lefthand acted as it did because that hand is controlled by thedisconnected right brain. Gazzaniga's experiment led himto theorize that the left brain acts an an interpreter.

Michael S. Gazzaniga '61, at the forefront of a new field of inquiry,divulges the inner workings of the human mind.

"Neuroscientists understand VERY LITTLE about howthe brain doesanything. If we TRULY understoodhow someone picksup a pencil, itwould represent a MAJOR advance"

"Take a look under the microscope at any SLAB OF BRAIN of any animal and you will STAGGER AWAY shaking your head. In the human brain there are 13 BILLION neurons with trillions of synaptic interactions. It DEFINES complexity."

The brain's hemispherescommunicate via thecorpus callosum. Severing itproduces the "split-brain"functioning that MichaelGazzaniga analyzes.

STILL BRAINSTORMING For at least 12 millennia thethinking animal has tried tofigure out what makes themind tick.4,000-500 B.C. Egyptians revere the heart as the seat of the soul and thought. Elsewhere, contemporaries believe that the liver houses intellect. Fourth century B.C. Hippocrates, father of medicine, concludes that the brain is the center of sensation. He diagnoses that "moistness" in the brain causes insanity. Two millennia later, researchers find that the brains of schizophrenics have abnormally large fluid-filled ventricles. Third century B.C. Plato regards the head as the place of the immortal soul. Aristotle attributes mental and emotional function to the heart. The brain, he says, cools the blood via the nose. 10,000 B.C. Neolithic surgeons drill holes in skulls, most likely to treat epilepsy, headaches, injuries, and to release evil spirits. 3,000 B.C. An Egyptian papyrus describes the convolutions of the brain. 300 B.C. Hemophilus of Chalcedon describes the ventricles of the brain and classifies nerves into sensory and motor categories. 300 B.C. Eristratus of Chios, father of physiology, connects the convolutions of the human brain with humans' superior intelligence. He theorizes brain function: Air from the lungs changes into vital spirits in the heart. The vital spirits enter the brain's ventricles and change into animal spirits, which travel through hollow nerves to move the body.