Human. Part 1

Michael S. Gazzaniga.

Human.

ACKNOWLEDGMENTS.

This book started a long time ago. Its origins are probably somewhere in the J. Alfred Prufrock house at Caltech, where I had the privilege of being in graduate school. That is what we called The House, and it had several bedrooms, one of which was mine. I can tell you the inhabitants of the other bedrooms were all much smarter and wiser than I. Most were physicists, and all went on to great careers. They thought hard about hard problems and they cracked many of them.

What was enduring about the experience for a young neophyte like me were the aspirations of these bright men. Work on the hard problems. Work, work, work. And I did, and I have. Paradoxically, the problem I have spent my life examining is much harder than theirs, which in a phrase is, what is the deal with humans? Oddly, they were fascinated with my problem, and at the same time, I couldn't get to first base with the conceptual tools they used on a moment-by-moment basis to tackle their own problems. While I used to whip my housemate, the physicist Norman Dombey, in chess, I remain to this day not at all confident that I truly understand the second law of thermodynamics. In fact, I know I don't. Yet Norman seemed to understand everything.

The atmosphere was suffused with the pervasive belief that the objective of the meaningful life is to gain insight into its mysteries. That was what was so contagious. So, here I am trying to do it again, some forty-five years later. And yet, not by myself, not by a long shot. The issue is trying to figure out what it means to be human. That is clear enough. So, to come out of the bullpen once more, I tapped into all the bright young students around me.

The journey started almost three years ago with my senior seminar during my last year at Dartmouth College. An extraordinary group of young men and women were a.s.signed topics I knew I wanted to explore, and they all bellied up to the bar with insights and juice. We hacked away at it for two months or so, and it was all deeply illuminating. Two of the students caught the fever, and I am happy to report that they are off to careers in the science of the mind.

The following year, I taught my first cla.s.s at the University of California, Santa Barbara, a university that doesn't apologize for being committed to research and scholars.h.i.+p. This was a cla.s.s of dedicated graduate students, and they too deepened and added insights to the evolving story. Then a funny thing happened.

It was determined I had prostate cancer and needed surgery. Let me tell you, that is a bad hair day, even when you are bald! And yet I fell into terrific medical hands and came through it with a good prognosis. Still, I was swamped with work, and by luck, my sister Rebecca Gazzaniga, perhaps the finest person who ever graced this earth, was ready to try something new. She is a physician, a botanist, a painter, a chef, a traveler, and everyone's favorite aunt. And now I discover she is a science junkie, a writer and editor and collaborator. A star has been born. Without her help, this book would not exist.

I have attempted to become a mouthpiece for the vast talents of many people, both students and family. I do it with pride and joy, as I still remember that special imperative of the Prufrock house at Caltech: Think about the big problems. It is not that they are grave. They are challenging, inspiring, and enduring. See what you think.

PROLOGUE.

I ALWAYS SMILE WHEN I HEAR GARRISON KEILLOR SAY, "BE well, do good work, and keep in touch." It is such a simple sentiment, yet so full of human complexity. Other apes don't have that sentiment. Think about it. Our species does like to wish people well, not harm. No one ever says, "Have a bad day" or "Do bad work," and keeping in touch is what the cell-phone industry has discovered all of us do, even when there is nothing going on.

There in one sentence Keillor captures humanness. A familiar cartoon with various captions makes its way around evolutionary biologists' circles. It shows an ape at one end of a line and then several intermediate early humans culminating in a tall human standing erect at the other end. We now know that the line isn't so direct, but the metaphor still works. We did evolve, and we are what we are through the forces of natural selection. And yet I would like to amend that cartoon. I see the human turning around with a knife in his hand and cutting his imaginary tether to the earlier versions, becoming liberated to do things no other animal comes close to doing.

We humans are special. All of us solve problems effortlessly and routinely. When we approach a screen door with our arms full of bags of groceries, we instantly know how to stick out our pinky and hook it around the door handle to open it. The human mind is so generative and so given to animation that we do things such as map agency (that is, we project intent) onto almost anything-our pets, our old shoes, our cars, our world, our G.o.ds. It is as if we don't want to be alone up here at the top of the cognitive chain as the smartest things on earth. We want to see our dogs charm us and appeal to our emotions; we imagine that they too can have pity, love, hate, and all the rest. We are a big deal and we are a little scared about it.

Thousands of scientists and philosophers over hundreds of years have either recognized this uniqueness of ours or have denied it and looked for the antecedents of everything human in other animals. In recent years, clever scientists have found antecedents to all kinds of things that we had a.s.sumed were purely human constructions. We used to think that only humans had the ability to reflect on their own thoughts, which is called metacognition. Well, think again. Two psychologists at the University of Georgia have shown that rats also have this ability. It turns out that rats know what they don't know. Does that mean we should do away with our rat traps? I don't think so.

Everywhere I look I see tidbits of differences, and one can always say a particular tidbit can be found in others aspects of biological life. Ralph Greenspan, a very talented neuroscientist and geneticist at the Neuroscience Inst.i.tute in La Jolla, California, studies, of all things, sleep in the fruit fly.

Someone had asked him at lunch one day, "Do flies sleep?" He quipped, "I don't know and I don't care." But then he got to thinking about it and realized that maybe he could learn something about the mysterious process of sleep, which has eluded understanding. The short version of this story is that flies do sleep, just as we do. More important, flies express the same genes during sleeping and waking hours that we do. Indeed, Greenspan's current research suggests that even protozoans sleep. Good grief!

The point is that most human activity can be related to antecedents in other animals. But to be swept away by such a fact is to miss the point of human experience. In the following chapters, we will comb through data about our brains, our minds, our social world, our feelings, our artistic endeavors, our capacity to confer agency, our consciousness, and our growing knowledge that our brain parts can be replaced with silicon parts. From this jaunt, one clear fact emerges. Although we are made up of the same chemicals, with the same physiological reactions, we are very different from other animals. Just as gases can become liquids, which can become solids, phase s.h.i.+fts occur in evolution, s.h.i.+fts so large in their implications that it becomes almost impossible to think of them as having the same components. A foggy mist is made up of the same stuff as an iceberg. In a complex relations.h.i.+p with the environment, very similar substances with the same chemical structure can become quite different in their reality and form.

Indeed, I have decided that something like a phase s.h.i.+ft has occurred in becoming human. There simply is no one thing that will ever account for our spectacular abilities, our aspirations, and our capacity to travel mentally in time to the almost infinite world beyond our present existence. Even though we have all of these connections with the biologic world from which we came, and we have in some instances similar mental structures, we are hugely different. While most of our genes and brain architecture are held in common with animals, there are always differences to be found. And while we can use lathes to mill fine jewelry, and chimpanzees can use stones to crack open nuts, the differences are light-years apart. And while the family dog may appear empathetic, no pet understands the difference between sorrow and pity.

A phase s.h.i.+ft occurred, and it occurred as the consequence of many things changing in our brains and minds. This book is the story of our uniqueness and how we got here. Personally, I love our species, and always have. I have never found it necessary to lessen our success and domination of this universe. So let us start the journey of understanding why humans are special, and let's have some fun doing it.

A NOTE ON SOURCE DOc.u.mENTATION.

The notes for this book were formatted according to the style doc.u.mented in the Publication Manual of the American Psychological a.s.sociation. At the time of this printing, the manual is in its fifth edition, and the APA format it details is a widely recognized standard for scientific writing in education and psychology.

Part I.

THE BASICS OF HUMAN LIFE.

Chapter 1.

ARE HUMAN BRAINS UNIQUE?.

The brain is the organ that sets us apart from any other species. It is not the strength of our muscles or of our bones that makes us different, it is our brain.

-Pasko T. Rakic, "Great Issues for Medicine in the Twenty-First Century," Annals of the New York Academy of Sciences 882 (1999), p. 66.

THE GREAT PSYCHOLOGIST DAVID PREMACK ONCE LAMENTED, "Why is it that the [equally great] biologist E. O. Wilson can spot the difference between two different kinds of ants at a hundred yards, but can't see the difference between an ant and a human?" The quip underlines strong differences of opinion on the issue of human uniqueness. It seems that half of the scientific world sees the human animal as on a continuum with other animals, and others see a sharp break between animals and humans, see two distinct groups. The argument has been raging for years, and it surely won't be settled in the near future. After all, we humans are either lumpers or splitters. We either see the similarities or prefer to note the differences.

I hope to illuminate the issue from a particular perspective. I think it is rather empty to argue that because, say, social behavior exists in humans and in ants, there is nothing unique about human social behavior. Both the F-16 and the Piper Cub are planes, both obey the laws of physics, both can get you from place A to place B, but they are hugely different. I want to begin by simply recognizing the huge differences between the human mind and brain and other minds and brains, seeing what structures, processes, and capacities are uniquely human.

It has always been a puzzle to me why so many neuroscientists become agitated when someone raises the question of whether or not there might be unique features to the human brain. Why is it that it is easy to accept that there are visible physical differences that make us unique, but to consider differences in our brains and how they work is so touchy? Recently, I asked a few neuroscientists the following question, "If you were recording electrical impulses from a slice of the hippocampus in a dish and you were not told if the slice came from a mouse, a monkey, or a human, would you be able to tell the difference? Put differently, is something unique about the human neuron? Would a future brain carpenter have to use that kind of neuron to build a human brain or would a monkey or mouse neuron do? Don't we all a.s.sume there is nothing unique about the neuron per se, that the special tricks of being human will come in the subtleties of the wiring diagram itself?"

The intensity of the response can be captured with just a couple of the replies. "A cell is a cell is a cell. It's a universal unit of processing that only scales in size between the bee and the human. If you scale appropriately a mouse, monkey, or human pyramidal cell you won't be able to say the difference even if you had Pythia to help you." So there! When we are studying the neurons of a mouse or an ant, we are studying mechanisms no different from a human neuron, period, end of story.

Here's another response: "There are differences in the types of neurons within a brain, and response properties of neurons within a brain. But across mammals-I think a neuron is a neuron. The inputs and outputs of that neuron (and synaptic composition) determine its function." Bang! Once again the physiology of the animal neuron is identical to that of a human. Without this a.s.sumption, it makes little sense to be studying these neurons so arduously. Of course there are similarities. But are there no differences?

Humans are unique. It is the how and the why that have been intriguing scientists, philosophers, and even lawyers for centuries. When we are trying to distinguish between animals and humans, controversies arise and battles are fought over ideas and the meaning of data, and when the smoke clears, we are left with more information on which to build stronger, tighter theories. Interestingly, in this quest, it appears that many opposing ideas are proving to be partially correct.

Although it is obvious to everyone that humans are physically unique, it is also obvious that we differ from other animals in far more complex aspects. We create art, pasta Bolognese, and complex machines, and some of us understand quantum physics. We don't need a neuroscientist to tell us that our brains are calling the shots, but we do need one to explain how it is done. How unique are we, and how are we unique?

How the brain drives our thoughts and actions has remained elusive. Among the many unknowns is the great mystery of how a thought moves from the depths of the unconscious to become conscious. As methods for studying the brain have become more sophisticated, some mysteries are solved, but it seems that solving one mystery often leads to the creation of many more. Brain imaging studies have caused some commonly accepted tenets to come into question and others to be completely discounted. For example, the idea that the brain works as a generalist, processing all input information equally and in the same manner and then mes.h.i.+ng it together, is less well accepted than it was even fifteen years ago. Brain imaging studies have revealed that specific parts of the brain are active for specific types of information. When you look at a tool (a man-made artifact created with a specific purpose in mind), your entire brain is not engaged in the problem of studying it; rather there is a specific area that is activated for tool inspection.

Findings in this realm lead to many questions. How many specific types of information are there, each with its own region? What is the specific information that activates each region? Why do we have specific regions for one type of activity and not another? And if we don't have a specific region for some type of information, what happens then? Although sophisticated imaging techniques can show us what part of the brain is involved with specific types of thoughts or actions, these scans tell us nothing of what is going on in that part of the brain. Today the cerebral cortex is thought to be "perhaps the most complex ent.i.ty known to science."1 The brain is complicated enough on its own, but the sheer number of different disciplines* that are studying it has produced thousands of domains of information. It is a wonder that order can be put to the mountain of data. Words used in one discipline often carry different meanings in others. Findings can become distorted through poor or incorrect interpretation and become unfortunate foundations or inaccurate reb.u.t.tals of theories that may take decades to be questioned and reevaluated. Politicians or other public figures can oftentimes misinterpret or ignore findings to support a particular agenda or stifle politically inconvenient research altogether. There is no need to be dispirited, though! Scientists are like a dog with a bone. They keep gnawing away, and sense is being made.

Let's start on our quest into human uniqueness the way it has been done in the past-by just looking at that brain. Can its appearance tell us anything special?

BIG BRAINS AND BIG IDEAS?.

Comparative neuroanatomy does what the name implies. It compares the brains of different species for size and structure. This is important, because in order to know what is unique in the human brain, or any other, for that matter, one needs to know how the various brains are alike and how they differ. This used to be an easy job and didn't take much in the way of equipment, maybe a good saw and a scale, which was about all that was available up until the middle of the nineteenth century. Then Charles Darwin published his Origin of Species, and the question of whether man had descended from apes was front and center. Comparative anatomy was in the limelight, and the brain was center stage.

Throughout the history of neuroscience, certain presumptions have been made. One of these is that the development of increased cognitive capacity is related to increased brain size over evolutionary time. This was the view held by Darwin, who wrote, "The difference between man and the higher animals, great as it is, is certainly one of degree and not of kind,"2 and by his ally, neuroanatomist T. H. Huxley, who denied that humans had any unique brain features other than size.3 The general acceptance of this notion, that all mammalian brains have the same components but that as the brain grew larger, its performance became more complex, led to the construction of the phylogenetic scale that some of us learned in school, with man sitting at the top of an evolutionary ladder, rather than out on the branch of a tree.1 However, Ralph Holloway, now a professor of anthropology at Columbia University, disagreed. In the mid-1960s, he suggested that evolutionary changes in cognitive capacity are the result of brain reorganization rather than changes in size alone.4 This disagreement about how the human brain differs from those of other animals, and indeed how the brains of other animals differ from each other-whether in quant.i.ty or in quality-continues.

Todd M. Preuss, a neuroscientist at Yerkes National Primate Research Center, points out why this disagreement is so controversial and why new discoveries of differences in connectivity have been considered "inconvenient."1 Many generalizations about cortical organization have been based on the "quant.i.ty" a.s.sumption. It has led scientists to believe that findings using models of brain structure found in other mammals, such as rats and monkeys, can be extrapolated to humans. If this is not correct, there are repercussions that reverberate into many other fields, such as anthropology, psychology, paleontology, sociology, and beyond. Preuss advocates comparative studies of mammalian brains rather than using the brain of a rat, say, as a model for how a human brain functions but on a lesser scale. He and many others have found that, on the microscopic level, mammalian brains differ widely from one another.5 Is this a.s.sumption about quant.i.ty correct? It would appear not. Many mammals have larger brains than humans in terms of absolute brain size. The blue whale has a brain that is five times larger than a human brain.6 Is it five times smarter? Doubtful. It has a larger body to control and a simpler brain structure. Although Captain Ahab may have found a whale intellectually stimulating (albeit he was dealing with a sperm whale, whose brain is also larger than a human's), it has not been a universal experience. So perhaps proportional (allometric) brain size is important: That is the size of the brain compared to the size of the body, often called relative brain size. Calculating brain-size differences this way puts a whale in its place, with a brain size that is only .01 percent of its body weight, compared to a human brain, which is 2 percent of body weight. At the same time, consider the pocket mouse's brain, which is 10 percent of its body weight. In fact, in the early nineteenth century, Georges Cuvier, an anatomist, stated, "All things being equal, the small animals have proportionately larger brains."6 As it turns out, proportional brain size increases predictably as body size decreases.

Human brains, however, are four to five times larger than would be expected for an average mammal of comparable size.7 In fact, in the hominid (ape) line in general (from which humans have evolved), brain size has increased much faster than body size. This is not true for other groups of primates, and the human brain has rocketed in size after the divergence from chimpanzees.8 Whereas a chimp's brain weighs about 400 grams, a human's brain is about 1,300 grams.6 So we do have big brains. Is this what is unique and can explain our intellect?

Remember Neanderthals? h.o.m.o neanderthalensis had a body ma.s.s comparable to that of h.o.m.o sapiens,9 but with a slightly larger cranial volume, measuring 1,520 cubic centimeters (cc) compared to the 1,340 cc typical of modern humans-so they too had a larger relative brain size than humans. Did they have a similar intelligence to humans? Neanderthals made tools and apparently imported raw materials from distant sites; they invented standardized techniques for making spears and tools10 and about 50,000 years ago began to paint their bodies and inter their dead.11 These activities are considered by many researchers to indicate some self-awareness and the beginnings of symbolic thought,6 which is important because that is believed to be the essential component of human speech.12 No one knows the extent of their speech capabilities, but what is clear is that Neanderthal material culture was not nearly as complex as that of contemporaneous h.o.m.o sapiens.13, 14 Although the bigger brain of the Neanderthals was not as capable of that of h.o.m.o sapiens, it was clearly more advanced than that of a chimp. The other problem with the big-brain theory is that h.o.m.o sapiens' brain size has decreased about 150 cc over the species' history, while their culture and social structures have become more complex. So perhaps relative brain size is important, but it is not the whole story, and since we are dealing with "perhaps the most complex ent.i.ty known to science," that should not surprise us at all.

From my own perspective on this issue, I have never been taken with the brain-size argument. For the past forty-five years I have been studying split-brain patients. These are patients who have had the two hemispheres of the brain surgically separated in an effort to control their epilepsy. Following their surgery, the left brain can no longer communicate meaningfully with the right brain, thus isolating one from the other. In effect, a 1,340-gram interconnected brain has become a 670-gram brain. What happens to intelligence?

Well, not much. What one sees is the specialization that we humans have developed over years of evolutionary change. The left hemisphere is the smart half of the brain. It speaks, thinks, and generates hypotheses. The right brain does not and is a poor symbolic cousin to the left. It does, on the other hand, have some skills that remain superior to those on the left, especially in the domain of visual perception. Yet, for present purposes, the overarching point is that the left hemisphere remains as cognitively adept as it was before it was disconnected from the right brain, leaving its 670 grams in the dust. Smart brains are derived from more than mere size.

Before we leave the question of brain size, there is some exciting new information from the field of genetics. Genetics research is revolutionizing many fields of study, including neuroscience. For those of us who are natural selection fans, it seems reasonable to a.s.sume that the explosion in human brain size is the result of natural selection, which works through many mechanisms. Genes are functional regions on chromosomes (microscopic threadlike structures that are found in the nucleus of all cells and are the carriers of hereditary characteristics), and those regions consist of DNA sequences.* Sometimes these sequences vary slightly, and as a result, the effect of that particular gene can vary in some way. These variant sequences are called alleles. Thus, a gene coding for flower color can vary in its DNA base pairs and result in a different flower color. When an allele has a highly important and positive effect on an organism such that it improves the organism's survival fitness or allows it to reproduce more, there is what is called a positive selection or directional selection for that allele. Natural selection would favor such a variant, and that particular allele would quickly become move common.

While not all genes' functions are known, there are many genes involved with the development of the human brain that are different from those of other mammals, and specifically from those of other primates. During embryonic development, these genes are involved in determining how many neurons there will be, as well as how big the brain will be. There is not much difference among species in the genes that do routine "housekeeping" in the nervous system, which are those that are involved in the most basic cellular functions, such as metabolism and protein synthesis.15 However, two genes have been identified that are specific regulators of brain size: microcephalin16 and ASPM (the abnormal spindle-like microcephaly-a.s.sociated gene).17 These genes were discovered because a defect in them causes a problem that is pa.s.sed on through birth to other family members. Defects in either of these genes lead to primary microcephaly, an autosomal recessive* neurodevelopmental disorder. Two princ.i.p.al features characterize this disorder: a markedly reduced head size that is the consequence of a small but architecturally normal brain, and nonprogressive mental r.e.t.a.r.dation. The genes were named for the disease that they cause if they are defective. It is the cerebral cortex (remember this point) that shows the greatest size reduction. In fact the brain size is so markedly decreased (three standard deviations below normal) that it is comparable in size to that of early hominids!18 Recent research from the laboratory of Bruce Lahn, a professor of genetics at the University of Chicago and the Howard Hughes Medical Inst.i.tute, has shown that both of these genes have undergone significant changes under the pressure of natural selection during the evolution of h.o.m.o sapiens. Microcephalin (without the defect) showed evidence of accelerated evolution along the entire primate lineage,19 and ASPM (also without the defect) has evolved most rapidly after the divergence of humans and chimpanzees,20 implicating these genes as the cause of the rapidly exploding brain size of our ancestors.

Accelerated evolution means what it sounds like. These genes were hot items that produced a characteristic that gave its owners an obvious compet.i.tive advantage. Whoever had them had more offspring, and the genes became dominant. Not resting on these findings, these researchers wondered if these genes could answer the question whether the human brain is continuing to evolve. It turns out that they could, and it is. The geneticists reasoned that if a gene has evolved adaptively in the making of the human species, like these genes that increase brain size, then it may still be doing so. How do you figure this out?

Scientists compared the genetic sequences of ethnically and geographically diverse people from around the world and found that the genes that code for the nervous system had some sequence differences (known as polymorphisms) among individuals. By a.n.a.lyzing human and chimpanzee polymorphism patterns and geographical distributions, using genetic probabilities and various other methods, they found evidence that some of these genes are experiencing ongoing positive selection in humans. They calculated that one genetic variant of microcephalin arose approximately 37,000 years ago, which coincides with the emergence of culturally modern humans, and it increased in frequency too rapidly to be compatible with random genetic drift or population migration. This suggests that it underwent positive selection.21 An ASPM variant arose about 5,800 years ago, coincident with the spread of agriculture, cities, and the first record of written language. It, too, is found in such high frequencies in the population as to indicate strong positive selection.22 This all sounds promising. We've got the big brains. Some of those big brains have discovered at least some of the genes that code for the big brains, and the genes appear to have changed at key times in our evolution. Doesn't this mean they caused it all to happen and that they are what make us unique? If you think the answer is going to be found in the beginning of the first chapter, you are not using that big brain of yours. We don't know if the genetic changes caused the cultural changes or were synergistic,23 and even if they did, what exactly is going on in those big brains and how is it happening? Is it happening only in ours or is it happening, but to a lesser extent, in our relatives the chimps?*

BRAIN STRUCTURE.

The structure of the brain can be looked at on three different levels: regions, cell types, and molecules. If you recall, I said that neuroanatomy used to be an easy job. The eminent experimental psychologist Karl Lashley once advised my mentor, Roger Sperry, "Don't teach. If you have to teach, teach neuroanatomy, because it never changes." Well, things have changed. Not only can sections of the brain be studied under the microscope with numerous different staining techniques that all reveal different information, but also a whole host of other chemical methods can be used, such as radioactive tracing, fluorescence, enzyme histochemical and immunohistochemical techniques, all sorts of scanners, and on and on. What is limiting now is actual material to study. Primate brains aren't easy to come by. Chimpanzees are on the endangered species list, gorilla and orangutan brains aren't any more abundant, and although there are an abundance of humans with brains, few seem to want to part with theirs. Many studies done on some species are invasive and terminal, not popular with h.o.m.o sapiens. Imaging studies are difficult to do on nonhuman species. It is so hard to get a gorilla to lie still. Even so, there are many tools, and even though huge amounts of information are being learned, not all that can be known is known. In fact, only a very small amount is known for sure. While this is great for neuroscientists' job security, the wide gaps in knowledge allow for speculation and differing opinions.

Brain Regions.

What do we know about the evolution of the brain? Has the entire brain increased in size equally, or have only specific areas of it increased?

Some definitions will be helpful. The cerebral cortex is the outer portion of the brain, about the size of a large dish towel that is pleated and laid over the rest of the brain. It consists of six layers of nerve cells and the pathways that connect them. The enlargement of the cerebral cortex accounts for most of the difference in the size of the brain between humans and other primates. The cortex is highly interconnected. Of all brain connections, 75 percent are within the cortex; the other 25 percent are input and output connections to other parts of the brain and nervous system.6 The neocortex is the evolutionarily newer region of the cerebral cortex and is where sensory perception, generation of motor commands, spatial reasoning, conscious thought, and, in us h.o.m.o sapiens, language take place. The neocortex is divided anatomically into four lobes-the frontal lobe and three posterior lobes-the parietal, the temporal, and the occipital. Everyone agrees that in primates, including humans, the neocortex is unusually large. The neocortex of a hedgehog is 16 percent of its brain by weight; in the Galago (a genus of small monkey) it is 46 percent; and in a chimpanzee, 76 percent. The neocortex in humans is even larger.6 What does it mean when part of the brain has enlarged? In proportional enlargement, all the parts are equally enlarged. If the brain is twice as large, every individual part of the brain is twice as large. In disproportionate enlargement, one part has enlarged more than the others. Usually, as brain regions change in size, their internal structure also changes, just like a business organization. You and your buddy build a new gizmo and sell a few of them. Once they become popular, you need to hire more people to make them, and then you need a secretary and a sales rep, and eventually you need specialists.

This also happens in the brain. As an area enlarges, it can produce subdivisions within a part of a structure that specializes in a particular activity. What is actually increasing when brain size increases is the number of neurons, but the size of the neurons is relatively constant among species. A neuron has connection capability to a limited number of other neurons. So although the number of neurons increases, they cannot increase the absolute number of connections each one makes. What tends to happen is that, as absolute brain size increases, the proportional connectivity decreases. Every neuron cannot connect to every other one. The human brain has billions of neurons that are organized into local circuits. If these circuits are stacked like a cake, they make up cortical regions; if they are bunched rather than stacked, they are called nuclei. Regions and nuclei are also interconnected to form systems. George Striedter6 at the University of California at Irvine suggests that size-related changes in connectivity may limit how large brains can become without being incoherent, and this may be the driving force behind evolutionary innovations that overcome this problem. Fewer dense connections force the brain to specialize, create local circuits, and automate. In general, though, according to Terrence Deacon, professor of biological anthropology and neuroscience at the University of California at Berkeley, the larger the area, the better connected it is.24 Now for the controversy: Is the neocortex evenly enlarged, or are some parts preferentially enlarged, and if so, which ones? Let's start with the occipital lobe, which contains, among other things, the primary visual, or striate, cortex. In chimps, it const.i.tutes 5 percent of the entire neocortex, whereas in humans it const.i.tutes 2 percent, which is less than would be expected. How to explain this? Did ours shrink, or did some other part of the neocortex enlarge? The striate cortex in fact is the exact size that it is predicted to be for an ape of our size. It appears then, that it is unlikely that it has shrunk; rather, some other parts of the cortex have expanded.7 The controversy lies in which parts have expanded.

The frontal lobe, until recently, was thought to be proportionally larger in humans than other primates. Earlier investigations of this subject were based on studies done on nonprimates, for the most part on non-ape primates, and inconsistent nomenclature and landmarks for different parts of the brain were used.25 Then Katerina s.e.m.e.ndeferi and colleagues26 published a study in 1997 comparing the sizes by volume of the frontal lobes of ten living humans with those of fifteen postmortem great apes (six chimpanzees, three bon.o.bos, two gorillas, four orangutans), four gibbons, and five monkeys (three rhesus, two cebus). This may seem like a small sample size, but in the world of comparative primate neuroanatomy it is quite large, and indeed included more samples than all previous studies. Their data concluded that although the absolute volume of the frontal lobe of humans was the greatest, the relative size of the frontal lobe across all the hominoids was similar. Thus they concluded that humans do not have a larger frontal lobe than expected for a primate with their brain size.

Why is this so important? The frontal lobe has much to do with the higher-functioning aspects of human behavior such as language and thought. If its relative size is no bigger in humans than in the other apes, how can we explain the increased functioning, such as language? These researchers had four suggestions: The region may have undergone a reorganization that includes enlargement of selected, but not all, cortical areas to the detriment of others.

The same neural circuits might be more richly interconnected within the frontal sectors themselves and between those sectors and other brain regions.

Subsectors of the frontal lobe might have undergone a modification of local circuitry.

Microscopic or macroscopic subsectors might have been added to the mix or dropped.

Todd Preuss argues that even if you accept that the frontal lobes did not expand out of proportion to the rest of the cortex, a distinction should be made between the frontal and the prefrontal cortex. The prefrontal cortex is the anterior part of the frontal lobe. It is distinguished from the rest of the frontal cortex by having an additional layer of neurons* and is implicated in planning complex cognitive behaviors, in personality, in memory, and in aspects of language and social behavior. He suggests that the percentage of frontal to prefrontal cortex may have changed. Preuss provides evidence that suggests that the motor cortex portion of a human's frontal lobe is smaller than the chimp's, implying that an expansion of a different part of the human's frontal cortex occurred to account for no overall loss in lobe size.1 In fact, s.e.m.e.ndeferi27 confirmed that area 10, in the lateral prefrontal cortex, is almost twice as large in humans as in apes. Area 10 is involved with memory and planning, cognitive flexibility, abstract thinking, initiating appropriate behavior and inhibiting inappropriate behavior, learning rules, and picking out relevant information from what is perceived through the senses. We will learn in later chapters that some of these abilities are much greater in humans, and some are unique.

Thomas Schoenemann and colleagues at the University of Pennsylvania were interested in the relative amount of white matter in the prefrontal cortex.28 The white matter lies beneath the cortex and is made up of nerve fibers connecting the cortex with the rest of the nervous system. They found that the prefrontal white matter was disproportionately larger in humans than other primates and concluded that this suggests a higher degree of connectivity in this part of the brain.

Connectivity is important. Supposing you were to set up an organization to locate a fugitive you suspected was driving across the country, what is the one thing you would need to have happen among all the law enforcement agencies that would be involved? Communication. It would do no good if the police in Louisiana knew to look for a blue Toyota and didn't tell anyone else, or a highway patrolman saw a suspicious car in El Paso going west, but didn't tell the patrol in New Mexico. With a lot of incoming information, the better the communication among investigators, the more effective the search will be.

This is also true of the prefrontal cortex. The more communication among its different parts, not only the faster it works, but the more flexible it is. What that means is that some information used for one task can be applied to something else. The more you know, the faster your brain works. Although we may share the same brain structures with the chimp, we get more bang out of our buck, and part of the reason may be the interconnections in the prefrontal cortex.

The prefrontal cortex is interesting in another way. Nonprimate mammals have two major regions of the prefrontal cortex, and primates have three. The original regions, which are present in other mammals and evolved earlier, are the orbital prefrontal region, which responds to external stimuli that are likely to be rewarding, and the anterior cingulate cortex, which processes information about the body's internal state. These two work together to contribute to the "emotional" aspects of decision making.29 The new region tacked on to these is called the lateral or granular prefrontal cortex, and it is where area 10 is.

This new region is apparently unique to primates and is concerned mainly with the rational aspects of decision making, which are our conscious efforts to reach a decision. This region is densely interconnected with other regions that are larger in human brains-the posterior parietal cortex and the temporal lobe cortex-and outside the neocortex, it is connected to several cell groups in the dorsal thalamus that are also disproportionately enlarged, the medial dorsal nucleus and the pulvinar. George Striedter suggests that what has enlarged is not a random group of areas and nuclei, but an entire circuit. He suggests that this circuit has made humans more flexible and capable of finding novel solutions to problems. Included in this circuit is the ability to inhibit automatic responses, necessary if one is to come up with novel responses.6 Leaving the frontal lobe, where most of the research has concentrated, we can't say much for the temporal and parietal lobes beyond that they are somewhat larger than expected, and they hold plenty of opportunities for PhD theses.

What about the rest of the brain? Is anything else enlarged? Well, the cerebellum is enlarged. The cerebellum is located posteriorly at the base of the brain, and it coordinates muscular activity. One part of the cerebellum, the dentate nucleus in particular, is larger than expected. This area receives input neurons from the lateral cerebellar cortex and sends output neurons to the cerebral cortex via the thalamus. (The thalamus sorts and directs sensory information arriving from other parts of the nervous system.) This is interesting because there is growing evidence that the cerebellum contributes to cognitive as well as motor function.

The Functional Story: Cortical Areas.

Besides being divided into physical parts such as lobes, the brain is also divided into functional units called cortical areas, which also have specific locations. It's interesting that Franz Joseph Gall, a German physician, first came up with this idea in the early 1800s. It was known as the theory of phrenology and was later expanded by other phrenologists. Gall's good idea was that the brain is the organ of the mind and that different brain areas did specific jobs. However, it led to the bad ideas that one could read a person's personality and character from the size of their various brain regions, that the shape of the skull would accurately correspond to the shape of the brain (which it does not), and that the size of these regions could be determined by palpating the skull. Phrenologists would run their hands over a person's skull; some even used calipers to make measurements. From these observations, they would predict the character of the individual. Phrenology was very popular and was used, among other things, to a.s.sess job applicants and to predict the characters of children. The trouble was, it didn't work. Gall's good idea does, though.

Cortical regions have neurons that share certain distinguis.h.i.+ng properties, such as that they respond to certain types of stimuli, are involved in certain types of cognitive tasks, or have the same microanatomy.* For instance there are separate cortical areas that process the sensory input from the eyes (the primary visual cortex, located in the occipital lobe) and from the ears (the primary auditory cortex, located in the temporal lobe). If there is damage to a primary sensory area, one no longer has the awareness of the sensual perception. If the auditory cortex is damaged, one no longer has the awareness of having heard a sound but may still react to a sound. Other cortical areas, called a.s.sociation areas, integrate various types of information. There are also motor areas, which specialize in specific aspects of voluntary movement.

Cortical areas in the frontal lobe are involved with impulse control, decision making and judgment, language, memory, problem solving, s.e.xual behavior, socialization, and spontaneity. The frontal lobe is the location of the brain's "executive," which plans, controls, and coordinates behavior and also controls voluntary movements of specific body parts, especially the hands.

What exactly is going on in the cortical areas of the parietal lobe is still a bit of a mystery, but they are involved with integrating sensory information from various parts of the body, with visual-spatial processing, and with the manipulation of objects. The primary auditory cortex, in the temporal lobe, is involved in hearing, and there are other areas involved with high-level auditory processing. In humans, areas in the left temporal lobe are specialized for language functions such as speech, language comprehension, naming things, and verbal memory. Prosody, or the rhythm of speech, is processed in the right temporal lobe. Areas in the ventral part of the temporal lobes also do some specific visual processing for faces, scenes, and object recognition. The medial parts are busy with memory for events, experiences, and facts. The hippocampi, which are evolutionarily ancient structures, are deep inside the temporal lobes and are thought to be involved in the process where short-term memory gets transferred to long-term memory and also spatial memory. The occipital lobe is involved with vision.

Since we can do so much more than those other apes, we definitely are going to find something unique here, don't you think? Primates have more cortical areas than other mammals. It has been found that they have nine or more premotor areas, the portions of the cortex that plan, select, and execute motor actions, whereas nonprimates have only two to four.6 It is tempting to think that because we humans are higher functioning, we would have more cortical areas than other primates. Indeed, very recent evidence indicates that unique areas have been found in the visual cortex of the human brain. David Heeger at New York University has just discovered these new areas, which are not found in other primates.* For the most part, however, additional cortical areas have not been found in humans.

How could it be that we don't have more cortical areas? What about language and cogitation? And how about, well, writing concertos and painting the Sistine Chapel-and NASCAR, for goodness' sake? If chimps have the same cortical areas that we do, why aren't they doing the same things? Shouldn't our language area at least be different? The answer may lie in how these areas are structured. They may be wired differently.

As it turns out, while our search is getting more and more complicated, it is also getting more interesting. Besides the fact that there is no evidence that humans have radically more cortical areas than apes, there is increasing evidence that there are equivalent cortical areas in apes for human-specific functions. It appears that other primates, not just the great apes, also have cortical areas that correspond to our language areas and tool-use areas,30 and that these areas are also lateralized, meaning that they are found predominately in one hemisphere rather than the other, just as they are in humans.31, 32 What has been found to be unique within the human brain is in an area called the planum temporale, which all primates have. This is a component of Wernicke's area, the cortical area a.s.sociated with language input, such as the comprehension of both written and spoken language.* The planum temporale is larger on the left side than the right side in humans, chimps, and rhesus monkeys, but it is microscopically unique in the left hemisphere of humans!33 Specifically what is different is that the cortical minicolumns of the planum temporale are larger and the area between the columns is wider on the left side of the human brain than on the right side, while in chimps and rhesus monkeys the columns and the intercolumnar s.p.a.ces are the same size on both sides of the brain.

So what have we got so far? We have brains that are bigger than expected for an ape, we have a neocortex that is three times bigger than predicted for our body size, we have some areas of the neocortex and the cerebellum that are larger than expected, we have more white matter, which means we probably have more connections, and now we have some microscopic differences in cortical minicolumns, whatever those are.

The Brain Under a Microscope.

Every time something is enlarged, it seems as if increased connectivity is involved. What are connections anyway? What are those columns? To answer that, we're going to the microscope. Remember that the cerebral cortex has six layers. These layers can be thought of as six sheets of neurons (impulse-conducting cells) stacked on top of each other. These sheets are not arranged haphazardly, but instead the individual neurons within a sheet line up with those in the sheets above and below to form columns (aka microcolumns or minicolumns) of cells that cross the sheets perpendicularly.33, 34, 35, 36, 37 This might sound as though it ends up looking like a wall of bricks, but these bricks are not rectangular; they are neurons known as pyramidal cells because of their shape. They actually look like Hershey's Kisses with hairs (dendrites) sticking out from them in all directions. The neurons that form these columns aren't just stacked on each other, but also form an elemental circuit and appear to function as a unit. It is widely accepted that neuronal columns are the fundamental processing unit within the cerebral cortex,37, 38 and a.s.sembling multiple columns together creates complex circuits within the cortex.39, 40 The cortex is organized into columns in all mammals. Along with the size of the cerebral cortex, the a.s.sociated number of columns within the cortex has historically been a major focus of evolutionary studies seeking to explain differences among species. Studies done at the close of the twentieth century have found that columnar cell numbers vary widely across mammalian species. Other studies have revealed that neurochemicals found within a column can also vary, not only across species but even across cortical locations within a species.41, 42, 43, 44, 45, 46 The connectional patterns of columns also vary. OK, so we have the six distinct layers, and they receive and send projections from and to specific sets of targets. The deepest cortical layers, the infragranular layers numbered V and VI, mature first during development (during gestation), and the neurons within these layers project primarily to targets outside the cortex. The most superficial layers, the supragranular layers (II and III), mature last,46 projecting primarily to other locations within the cortex,47, 48, 49 and they are thicker in primates than other species.50 Several scientists have suggested that the supragranular layers, and the network of connections they form between cortical locations, partic.i.p.ate heavily in higher cognitive functions. This is accomplished by linking motor, sensory, and a.s.sociation areas. These areas receive sensory inputs from high-order sensory systems, interpret them in the light of similar past experiences, and function in reasoning, judgment, emotions, verbalizing ideas, and storing memory.50, 51 It is also suggested that the differential thickness of these layers may imply an unequal degree of connectivity,49, 52 which could play a role in the cognitive and behavioral differences among various species.43 For example: The average relative thickness of the supragranular layer in a rodent is 19 percent, while in a primate it is 46 percent.53 Let's put it another way. Picture this: Take the Hershey's Kisses with hairs sticking out from each of them and stack them on top of each other, and you have a minicolumn. Gather several stacks together in a bundle, and these bundles are the cortical columns. Now take thousands of these bundles of Hershey's Kisses and pack them together. How much s.p.a.ce they are going to take up and how they are arranged will depend on how thick each stack is, how dense the hairs are around each stack, how many individual stacks of Kisses are in a bundle, how tightly they are packed (which is also dependent on how the Kisses will wedge together), how many bundles you have, and how tall the bundles are. There are a lot of variables, and they all matter and ultimately are thought to contribute to our cognitive and behavioral abilities. What is determining how many Kisses we have?

The horizontal expansion of the cortical sheet (the dish towel) and alterations to the basic structure of cortical columns are likely determined early in fetal development by altering the number and timing of cell divisions that generate cortical neurons. Cortical neurogenesis can be divided into an early and a late period. The length of time and the number of cell cycles spent in the early period of cell division will ultimately determine the number of cortical columns that will be found in any given species.54 The length of time and the number of cell cycles spent in the later period may determine the number of individual neurons within a cortical column. A higher number of early divisions will result in a larger cortical sheet (bigger dish towel), and a higher number of later divisions will result in a higher number of neurons within an individual column. The time spent generating neurons in a given species correlates highly with supragranular layer thickness55; thus, it is possible that changes to the absolute time of neurogenesis and the number of cell cycles that occur during neurogenesis dictate the pattern of the neuron sheets in a species, and the size of the supragranular layers. Changes in timing during the production of the neurons could produce dramatic changes in cortical structure.56, 57, 58, 59 And what controls the timing? DNA. That is going to take us deep into the world of genetics, but we aren't going there yet.

The Areas of Specialization.

Now that we know what minicolumns are, we are going to look at how this asymmetry of the columns found in the planum temporale (you almost forgot about that, didn't you?) relates to function and if it really has anything to do with humans' being unique. The speech center is located in the left hemisphere's auditory cortex. Acoustic stimuli are received by the ear, where they are converted to electric impulses and sent to the primary auditory cortex, in both hemispheres. The auditory cortex is made up of several parts, each of which have a different structure and job. For instance some neurons in the auditory cortex are sensitive to various frequencies of sound and some to loudness. The number, location, and organization of these parts in the human auditory cortex are not fully understood. As far as speech is concerned, each hemisphere is concerned with different aspects. Wernicke's area in the left hemisphere recognizes distinctive parts of speech, and an area in the right auditory cortex recognizes prosody, the metrical structure of speech, which we will talk about in later chapters, and then sends this info to Wernicke's area.

We are now entering the realm of speculation. We know for sure that the human planum temporale (a component of Wernicke's area) is larger in the left hemisphere than the right, and the microscopic architecture is different on the left side compared to the right. The minicolumns are wider, and the s.p.a.ces between them are greater, and this lateralized change in architecture is unique to humans. With the increased s.p.a.ce between minicolumns, there is also an increase in the spread of the dendrites from the pyramidal cells (the hairs of the Hershey's Kisses), but the increase is not proportional to the increase in s.p.a.cing. This results in a smaller number of minicolumns being interconnected than in the right hemisphere, and it has been proposed that this could indicate that there is a more elaborate and less redundant pattern of local processing architecture in this area in the left hemisphere. It may also indicate that there is an additional const.i.tuent in this s.p.a.ce.1 This scenario is different in the other auditory regions. There the dendritic spread of the pyramidal cells did compensate for the increased s.p.a.cing (that is, the hairs on the Hershey's Kisses got longer and filled in the increased s.p.a.ce between the stacks of Kisses).

The posterior language region also differs between the two hemispheres at the macrocolumn level. The two hemispheres have equal-size areas of patchy interconnections, but the distance between the patches is greater in the left hemisphere, indicating that there are more interconnected macrocolumns in the left. It has been speculated that this pattern of interconnections is similar to that in the visual cortex, where interconnected macrocolumns that process similar types of information are also cl.u.s.tered together. Thus, perhaps the presence of greater connectivity in the posterior auditory system creates similarly functioning cl.u.s.ters that can a.n.a.lyze incoming information on a finer scale.1 So far, there is no direct evidence of hemispheric asymmetry in the connections between regions, owing to technical limitations in studying the long-distance connections of human brains, but there is some indirect evidence. The increased distance between the minicolumns could be caused partly by differences in the incoming and outgoing connections-either increases in numbers or size. There are consistent shape differences between the two hemispheres, and long- and short-range neurons are known to contribute to the shape of the brain's convolutions.

And one last thing: There is an increased number of extra-large pyramidal cells in the supragranular layer on the left side in the anterior and posterior language areas, as well as in the primary and secondary auditory locations. Many researchers have suggested that this is indicative of connectional asymmetries and may play a role in temporal processing, and that is a big deal.

We all know that timing is important. Just ask Steve Martin or Rita Rudner. The left hemisphere is better at processing temporal information. Because timing is essential to the comprehension of language, the human brain may require specialized connections to process it. It has even been suggested that the costs of a time delay in sending information across hemispheres has been the driving force in language lateralization.60 Lateralization and Connectivity.

To be sure, the human brain is a bizarre device, set in place through natural selection for one main purpose-to make decisions that enhance reproductive success. That simple fact has many consequences and is at the heart of evolutionary biology. Once grasped, it helps the brain scientist to understand a major phenomenon of human brain function-its ubiquitous lateral cerebral specialization. Nowhere else in the animal kingdom is there such rampant specialization of function. Why is this, and how did it come about?

Or, as Kevin Johnson, a friend of my sister's, put it, "So the brain is composed of two halves that need to interact to create a working mind. Now, if we a.s.sume that both brain and mind are the result of evolutionary forces, what is the adaptive advantage of a bicameral brain? What evolutionary force could possibly make such a wacky arrangement adaptive?" What emerges from my own split-brain research is a possible insight to these questions.

THE WACKY ARRANGEMENT.