Neuroscience: Past, Present, and Future
Views of the Brain from the Renaissance to the Nineteenth Century
Localization of Specific Functions to Different Parts of the Brain
The Neuron: The Basic Functional Unit of the Brain
Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrows, griefs, despondency, and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear and know what are foul and what are fair, what are bad and what are good, what are sweet and what are unsavory. . . . And by the same organ we become mad and delirious, and fears and terrors assail us. . . . All these things we endure from the brain when it is not healthy. . . . In these ways I am of the opinion that the brain exercises the greatest power in the man.
—Hippocrates, On the Sacred Disease (Fourth century B.C.E.)
It is human nature to be curious about how we see and hear; why some things feel good and others hurt; how we move; how we reason, learn, remember, and forget; and the nature of anger and madness. Neuroscience research is unraveling these mysteries, and the conclusions of this research are the subject of this textbook.
The word “neuroscience” is young. The Society for Neuroscience, an association of professional neuroscientists, was founded only relatively recently in 1970. The study of the brain, however, is as old as science itself. Historically, the scientists who devoted themselves to an understanding of the nervous system came from different scientific disciplines: medicine, biology, psychology, physics, chemistry, mathematics. The neuroscience revolution occurred when scientists realized that the best hope for understanding the workings of the brain would come from an interdisciplinary approach, a combination of traditional approaches to yield a new synthesis, a new perspective. Most people involved in the scientific investigation of the nervous system today regard themselves as neuroscientists. Indeed, while the course you are now taking may be sponsored by the psychology or biology department at your university or college and may be called biopsychology or neurobiology, you can bet that your instructor is a neuroscientist.
The Society for Neuroscience is one of the largest and fastest growing associations of professional scientists. Far from being overly specialized, the field is as broad as nearly all of natural science, with the nervous system serving as the common point of focus. Understanding how the brain works requires knowledge about many things, from the structure of the water molecule to the electrical and chemical properties of the brain to why Pavlov’s dog salivated when a bell rang. This book explores the brain with this broad perspective.
We begin the adventure with a brief tour of neuroscience. What have scientists thought about the brain over the ages? Who are the neuroscientists of today, and how do they approach studying the brain?
You probably already know that the nervous system—the brain, spinal cord, and nerves of the body—is crucial for life and enables you to sense, move, and think. How did this view arise?
Evidence suggests that even our prehistoric ancestors appreciated that the brain was vital to life. The archeological record includes many hominid skulls, dating back a million years and more, that bear signs of fatal cranial damage likely inflicted by other hominids. As early as 7000 years ago, people were boring holes in each other’s skulls (a process called trepanation), evidently with the aim not to kill but to cure (Figure 1.1). These skulls show signs of healing after the operation, indicating that this procedure had been carried out on live subjects rather than being a ritual conducted after death. Some individuals apparently survived multiple skull surgeries. What those early surgeons hoped to accomplish is not clear, although it has been speculated that this procedure may have been used to treat headaches or mental disorders, perhaps by giving the evil spirits an escape route.
FIGURE 1.1 Evidence of prehistoric brain surgery. This skull of a man over 7000 years old was surgically opened while he was still alive. The arrows indicate two sites of trepanation. (Source: Alt et al., 1997, Fig. 1a.)
Recovered writings from the physicians of ancient Egypt, dating back almost 5000 years, indicate that they were well aware of many symptoms of brain damage. However, it is also very clear that the heart, not the brain, was considered to be the seat of the soul and the repository of memories. Indeed, while the rest of the body was carefully preserved for the afterlife, the brain of the deceased was simply scooped out through the nostrils and discarded! The view that the heart was the seat of consciousness and thought was not seriously challenged until the time of Hippocrates.
Consider the idea that the different parts of your body look different because they serve different purposes. The structures of the feet and hands are very different, for example, because they perform very different functions: We walk on our feet and manipulate objects with our hands. Thus, there appears to be a very clear correlation between structure and function. Differences in appearance predict differences in function.
What can we glean about function from the structure of the head? Quick inspection and a few simple experiments (like closing your eyes) reveal that the head is specialized for sensing the environment with the eyes and ears, nose, and tongue. Even crude dissection can trace the nerves from these organs through the skull into the brain. What would you conclude about the brain from these observations?
If your answer is that the brain is the organ of sensation, then you have reached the same conclusion as several Greek scholars of the fourth century B.C.E. The most influential scholar was Hippocrates (460–379 B.C.E.), the father of Western medicine, who believed that the brain was not only involved in sensation but was also the seat of intelligence.
This view was not universally accepted, however. The famous Greek philosopher Aristotle (384–322 B.C.E.) clung to the belief that the heart was the center of intellect. What function did Aristotle reserve for the brain? He believed it was a radiator for cooling blood that was overheated by the seething heart. The rational temperament of humans was thus explained by the large cooling capacity of our brain.
The most important figure in Roman medicine was the Greek physician and writer Galen (130–200 C.E.), who embraced the Hippocratic view of brain function. As physician to the gladiators, he must have witnessed the unfortunate consequences of spine and brain injuries. However, Galen’s opinions about the brain were probably influenced more by his many careful animal dissections. Figure 1.2 is a drawing of the brain of a sheep, one of Galen’s favorite subjects. Two major parts are evident: the cerebrum in the front and the cerebellum in the back. (The structure of the brain is described in Chapter 7.) Just as we can deduce function from the structure of the hands and feet, Galen tried to deduce function from the structure of the cerebrum and the cerebellum. Poking the freshly dissected brain with a finger reveals the cerebellum is rather hard and the cerebrum rather soft. From this observation, Galen suggested that the cerebrum must receive sensations while the cerebellum must command the muscles. Why such a distinction? He recognized that to form memories, sensations must be imprinted in the brain. Naturally, this must occur in the doughy cerebrum.
FIGURE 1.2 The brain of a sheep. Notice the location and appearance of the cerebrum and the cerebellum.
As improbable as his reasoning may seem, Galen’s deductions were not that far from the truth. The cerebrum, in fact, is largely concerned with sensation and perception, and the cerebellum is primarily a movement control center. Moreover, the cerebrum is a repository of memory. We will see that this is not the only example in the history of neuroscience in which the right general conclusions were reached for the wrong reasons.
How does the brain receive sensations and move the limbs? Galen cut open the brain and found that it is hollow (Figure 1.3). In these hollow spaces, called ventricles (like the similar chambers in the heart), there is fluid. To Galen, this discovery fit perfectly with the prevailing theory that the body functioned according to a balance of four vital fluids, or humors. Sensations were registered and movements initiated by the movement of humors to or from the brain ventricles via the nerves, which were believed to be hollow tubes, like the blood vessels.
FIGURE 1.3 A dissected sheep brain showing the ventricles.
Views of the Brain from the Renaissance to the Nineteenth Century
Galen’s view of the brain prevailed for almost 1500 years. During the Renaissance, the great anatomist Andreas Vesalius (1514–1564) added more detail to the structure of the brain (Figure 1.4). However, the ventricular theory of brain function remained essentially unchallenged. Indeed, the whole concept was strengthened in the early seventeenth century, when French inventors built hydraulically controlled mechanical devices. These devices supported the notion that the brain could be machinelike in its function: Fluid forced out of the ventricles through the nerves might literally “pump you up” and cause the movement of the limbs. After all, don’t the muscles bulge when they contract?
FIGURE 1.4 Human brain ventricles depicted during the Renaissance. This drawing is from De humani corporis fabrica by Vesalius (1543). The subject was probably a decapitated criminal. Great care was taken to be anatomically correct in depicting the ventricles. (Source: Finger, 1994, Fig. 2.8.)
A chief advocate of this fluid–mechanical theory of brain function was the French mathematician and philosopher René Descartes (1596–1650). Although he thought this theory could explain the brain and behavior of other animals, Descartes believed it could not possibly account for the full range of human behavior. He reasoned that unlike other animals, people possess intellect and a God-given soul. Thus, Descartes proposed that brain mechanisms control only human behavior that is like that of the beasts. Uniquely human mental capabilities exist outside the brain in the “mind.” Descartes believed that the mind is a spiritual entity that receives sensations and commands movements by communicating with the machinery of the brain via the pineal gland (Figure 1.5). Today, some people still believe that there is a “mind–brain problem,” that somehow the human mind is distinct from the brain. However, as we shall see in Part III, modern neuroscience research supports a different conclusion: The mind has a physical basis, which is the brain.
FIGURE 1.5 The brain according to Descartes. This drawing appeared in a 1662 publication by Descartes, who thought that hollow nerves from the eyes projected to the brain ventricles. The mind influenced the motor response by controlling the pineal gland (H), which worked like a valve to control the movement of animal spirits through the nerves that inflated the muscles. (Source: Finger, 1994, Fig. 2.16.)
Fortunately, other scientists during the seventeenth and eighteenth centuries broke away from the traditional focus on the ventricles and began examining the brain’s substance more closely. They observed, for example, two types of brain tissue: the gray matter and the white matter (Figure 1.6). What structure–function relationship did they propose? White matter, because it was continuous with the nerves of the body, was correctly believed to contain the fibers that bring information to and from the gray matter.
FIGURE 1.6 White matter and gray matter. The human brain has been cut open to reveal these two types of tissue.
By the end of the eighteenth century, the nervous system had been completely dissected and its gross anatomy described in detail. Scientists recognized that the nervous system has a central division, consisting of the brain and spinal cord, and a peripheral division, consisting of the network of nerves that course through the body (Figure 1.7). An important breakthrough in neuroanatomy came with the observation that the same general pattern of bumps (called gyri) and grooves (called sulci and fissures) can be identified on the surface of the brain in every individual (Figure 1.8). This pattern, which enables the parceling of the cerebrum into lobes, led to speculation that different functions might be localized to the different bumps on the brain. The stage was now set for the era of cerebral localization.
FIGURE 1.7 The basic anatomical subdivisions of the nervous system. The nervous system consists of two divisions, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord. The three major parts of the brain are the cerebrum, the cerebellum, and the brain stem. The PNS consists of the nerves and nerve cells that lie outside the brain and spinal cord. Description
FIGURE 1.8 The lobes of the cerebrum. Notice the deep Sylvian fissure, dividing the frontal lobe from the temporal lobe, and the central sulcus, dividing the frontal lobe from the parietal lobe. The occipital lobe lies at the back of the brain. These landmarks can be found on all human brains. Description
Let’s review how the nervous system was understood at the end of the eighteenth century:
- Injury to the brain can disrupt sensations, movement, and thought and can cause death.
- The brain communicates with the body via the nerves.
- The brain has different identifiable parts, which probably perform different functions.
- The brain operates like a machine and follows the laws of nature.
During the next 100 years, more would be learned about the function of the brain than had been learned in all of previous recorded history. This work provided the solid foundation on which modern neuroscience rests. Now we’ll look at four key insights gained during the nineteenth century.
Nerves as Wires. In 1751, Benjamin Franklin published a pamphlet titled Experiments and Observations on Electricity, which heralded a new understanding of electrical phenomena. By the turn of the century, Italian scientist Luigi Galvani and German biologist Emil du Bois-Reymond had shown that muscles can be caused to twitch when nerves are stimulated electrically and that the brain itself can generate electricity. These discoveries finally displaced the notion that nerves communicate with the brain by the movement of fluid. The new concept was that the nerves are “wires” that conduct electrical signals to and from the brain.
Unresolved was whether the signals to the muscles causing movement use the same wires as those that register sensations from the skin. Bidirectional communication along the same wires was suggested by the observation that when a nerve in the body is cut, there is usually a loss of both sensation and movement in the affected region. However, it was also known that within each nerve of the body there are many thin filaments, or nerve fibers, each one of which could serve as an individual wire carrying information in a different direction.
This question was answered around 1810 by Scottish physician Charles Bell and French physiologist François Magendie. A curious anatomical fact is that just before the nerves attach to the spinal cord, the fibers divide into two branches, or roots. The dorsal root enters toward the back of the spinal cord, and the ventral root enters toward the front (Figure 1.9). Bell tested the possibility that these two spinal roots carry information in different directions by cutting each root separately and observing the consequences in experimental animals. He found that cutting only the ventral roots caused muscle paralysis. Later, Magendie was able to show that the dorsal roots carry sensory information into the spinal cord. Bell and Magendie concluded that within each nerve is a mixture of many wires, some of which bring information into the brain and spinal cord and others that send information out to the muscles. In each sensory and motor nerve fiber, transmission is strictly one-way. The two kinds of fibers are bundled together for most of their length, but they are anatomically segregated where they enter or exit the spinal cord.
FIGURE 1.9 Spinal nerves and spinal nerve roots. Thirty-one pairs of nerves leave the spinal cord to supply the skin and the muscles. Cutting a spinal nerve leads to a loss of sensation and a loss of movement in the affected region of the body. Incoming sensory fibers (red) and outgoing motor fibers (blue) divide into spinal roots where the nerves attach to the spinal cord. Bell and Magendie found that the ventral roots contain only motor fibers and the dorsal roots contain only sensory fibers. Description
Localization of Specific Functions to Different Parts of the Brain. If different functions are localized in different spinal roots, then perhaps different functions are also localized in different parts of the brain. In 1811, Bell proposed that the origin of the motor fibers is the cerebellum and the destination of the sensory fibers is the cerebrum.
How would you test this proposal? One way is to use the same approach that Bell and Magendie employed to identify the functions of the spinal roots: to destroy these parts of the brain and test for sensory and motor deficits. This approach, in which parts of the brain are systematically destroyed to determine their function, is called the experimental ablation method. In 1823, the esteemed French physiologist Marie-Jean-Pierre Flourens used this method in a variety of animals (particularly birds) to show that the cerebellum does indeed play a role in the coordination of movement. He also concluded that the cerebrum is involved in sensation and perception, as Bell and Galen before him had suggested. Unlike his predecessors, however, Flourens provided solid experimental support for his conclusions.
What about all those bumps on the brain’s surface? Do they perform different functions as well? The idea that they do was irresistible to a young Austrian medical student named Franz Joseph Gall. Believing that bumps on the surface of the skull reflect bumps on the surface of the brain, Gall proposed in 1809 that the propensity for certain personality traits, such as generosity, secretiveness, and destructiveness, could be related to the dimensions of the head (Figure 1.10). To support his claim, Gall and his followers collected and carefully measured the skulls of hundreds of people representing an extensive range of personality types, from the very gifted to the criminally insane. This new “science” of correlating the structure of the head with personality traits was called phrenology. Although the claims of the phrenologists were never taken seriously by the mainstream scientific community, they did capture the popular imagination of the time. In fact, a textbook on phrenology published in 1827 sold over 100,000 copies.
FIGURE 1.10 A phrenological map. According to Gall and his followers, different behavioral traits could be related to the size of different parts of the skull. (Source: Clarke and O’Malley, 1968, Fig. 118.)
One of the most vociferous critics of phrenology was Flourens, the same man who had shown experimentally that the cerebellum and cerebrum perform different functions. His grounds for criticism were sound. For one thing, the shape of the skull is not correlated with the shape of the brain. In addition, Flourens performed experimental ablations showing that particular traits are not isolated to the portions of the cerebrum specified by phrenology. Flourens also maintained, however, that all regions of the cerebrum participate equally in all cerebral functions, a conclusion later shown to be erroneous.
The person usually credited with tilting the scales of scientific opinion firmly toward localization of functions in the cerebrum was French neurologist Paul Broca (Figure 1.11). Broca was presented with a patient who could understand language but could not speak. After the man’s death in 1861, Broca carefully examined his brain and found a lesion in the left frontal lobe (Figure 1.12). Based on this case and several others like it, Broca concluded that this region of the human cerebrum was specifically responsible for the production of speech.
FIGURE 1.11 Paul Broca (1824–1880). By carefully studying the brain of a man who had lost the faculty of speech after a brain lesion (see Figure 1.12), Broca became convinced that different functions could be localized to different parts of the cerebrum. (Source: Clarke and O’Malley, 1968, Fig. 121.)
FIGURE 1.12 The brain that convinced Broca of localization of function in the cerebrum. This is the preserved brain of a patient who had lost the ability to speak before he died in 1861. The lesion that produced this deficit is circled. (Source: Corsi, 1991, Fig. III, 4.)
Solid experimental support for cerebral localization in animals quickly followed. German physiologists Gustav Fritsch and Eduard Hitzig showed in 1870 that applying small electrical currents to a circumscribed region of the exposed surface of the brain of a dog could elicit discrete movements. Scottish neurologist David Ferrier repeated these experiments with monkeys. In 1881, he showed that removal of this same region of the cerebrum causes paralysis of the muscles. Similarly, German physiologist Hermann Munk using experimental ablation found evidence that the occipital lobe of the cerebrum was specifically required for vision.
As you will see in Part II of this book, we now know that there is a very clear division of labor in the cerebrum, with different parts performing very different functions. Today’s maps of the functional divisions of the cerebrum rival even the most elaborate of those produced by the phrenologists. The big difference is that unlike the phrenologists, scientists today require solid experimental evidence before attributing a specific function to a portion of the brain. All the same, Gall seems to have had in part the right general idea. It is natural to wonder why Flourens, the pioneer of brain localization of function, was misled into believing that the cerebrum acted as a whole and could not be subdivided. This gifted experimentalist may have missed cerebral localization for many different reasons, but it seems clear that one reason was his visceral disdain for Gall and phrenology. He could not bring himself to agree even remotely with Gall, whom he viewed as a lunatic. This reminds us that science, for better or worse, was and still is subject to both the strengths and the weaknesses of human nature.
The Evolution of Nervous Systems. In 1859, English biologist Charles Darwin (Figure 1.13) published On the Origin of Species. This landmark work articulates a theory of evolution: that species of organisms evolved from a common ancestor. According to his theory, differences among species arise by a process Darwin called natural selection. As a result of the mechanisms of reproduction, the physical traits of the offspring are sometimes different from those of the parents. If such traits hold an advantage for survival, the offspring themselves will be more likely to survive to reproduce, thus increasing the likelihood that the advantageous traits are passed on to the next generation. Over the course of many generations, this process led to the development of traits that distinguish species today: flippers on harbor seals, paws on dogs, hands on raccoons, and so on. This single insight revolutionized biology. Today, scientific evidence in many fields ranging from anthropology to molecular genetics overwhelmingly supports the theory of evolution by natural selection.
FIGURE 1.13 Charles Darwin (1809–1882). Darwin proposed his theory of evolution, explaining how species evolve through the process of natural selection. (Source: The Bettman Archive.)
Darwin included behavior among the heritable traits that could evolve. For example, he observed that many mammalian species show the same reaction when frightened: The pupils of the eyes get bigger, the heart races, hairs stand on end. This is as true for a human as it is for a dog. To Darwin, the similarities of this response pattern indicated that these different species evolved from a common ancestor that possessed the same behavioral trait, which was advantageous presumably because it facilitated escape from predators. Because behavior reflects the activity of the nervous system, we can infer that the brain mechanisms that underlie this fear reaction may be similar, if not identical, across these species.
The idea that the nervous systems of different species evolved from common ancestors and may have common mechanisms is the rationale for relating the results of animal experiments to humans. For example, many of the details of electrical impulse conduction along nerve fibers were discovered first in the squid but are now known to apply equally well to humans. Most neuroscientists today use animal models to examine processes they wish to understand in humans. For example, rats show clear signs of addiction if they are repeatedly given the chance to self-administer cocaine. Consequently, rats provide a valuable animal model for research focused on understanding how psychoactive drugs exert their effects on the nervous system.
On the other hand, many behavioral traits are highly specialized for the environment (or niche) a species normally occupies. For example, monkeys swinging from branch to branch have a keen sense of sight, while rats slinking through underground tunnels have poor vision but a highly evolved sense of touch using their snout whiskers. Adaptations are reflected in the structure and function of the brain of every species. By comparing the specializations of the brains of different species, neuroscientists have been able to identify which parts of the brain are specialized for different behavioral functions. Examples for monkeys and rats are shown in Figure 1.14.
FIGURE 1.14 Different brain specializations in monkeys and rats. (a) The brain of the macaque monkey has a highly evolved sense of sight. The boxed region receives information from the eyes. When this region is sliced open and stained to show metabolically active tissue, a mosaic of “blobs” appears. The neurons within the blobs are specialized to analyze colors in the visual world. (b) The brain of a rat has a highly evolved sense of touch to the face. The boxed region receives information from the whiskers. When this region is sliced open and stained to show the location of the neurons, a mosaic of “barrels” appears. Each barrel is specialized to receive input from a single whisker on the rat’s face. (Photomicrographs courtesy of Dr. S.H.C. Hendry.) Description
The Neuron: The Basic Functional Unit of the Brain. Technical advances in microscopy during the early 1800s gave scientists their first opportunity to examine animal tissues at high magnifications. In 1839, German zoologist Theodor Schwann proposed what came to be known as the cell theory: All tissues are composed of microscopic units called cells.
Although cells in the brain had been identified and described, there was still controversy at that time about whether the individual “nerve cell” was actually the basic unit of brain function. Nerve cells usually have a number of thin projections, or processes, that extend from a central cell body (Figure 1.15). Initially, scientists could not decide whether the processes from different cells fuse together as do blood vessels in the circulatory system. If this were true, then the “nerve net” of connected nerve cells would represent the elementary unit of brain function.
FIGURE 1.15 An early depiction of a nerve cell. Published in 1865, this drawing by German anatomist Otto Deiters shows a nerve cell, or neuron, and its many projections, called neurites. For a time it was thought that the neurites from different neurons might fuse together like the blood vessels of the circulatory system. We now know that neurons are distinct entities that communicate using chemical and electrical signals. (Source: Clarke and O’Malley, 1968, Fig. 16.)
Chapter 2 presents a brief history of how this issue was resolved. Suffice it to say that by 1900, the individual nerve cell, now called the neuron, was recognized to be the basic functional unit of the nervous system.
The history of modern neuroscience is still being written, and the accomplishments to date form the basis for this textbook. We will discuss the most recent developments in the coming chapters. Before we do, let’s take a look at how brain research is conducted today and why it is so important to society.
History has clearly shown that understanding how the brain works is a big challenge. To reduce the complexity of the problem, neuroscientists break it into smaller pieces for systematic experimental analysis. This is called the reductionist approach. The size of the unit of study defines what is often called the level of analysis. In ascending order of complexity, these levels are molecular, cellular, systems, behavioral, and cognitive.
Molecular Neuroscience. The brain has been called the most complex piece of matter in the universe. Brain matter consists of a fantastic variety of molecules, many of which are unique to the nervous system. These different molecules play many different roles that are crucial for brain function: messengers that allow neurons to communicate with one another, sentries that control what materials can enter or leave neurons, conductors that orchestrate neuron growth, archivists of past experiences. The study of the brain at this most elementary level is called molecular neuroscience.
Cellular Neuroscience. The next level of analysis is cellular neuroscience, which focuses on studying how all those molecules work together to give neurons their special properties. Among the questions asked at this level are: How many different types of neurons are there, and how do they differ in function? How do neurons influence other neurons? How do neurons become “wired together” during fetal development? How do neurons perform computations?
Systems Neuroscience. Constellations of neurons form complex circuits that perform a common function, such as vision or voluntary movement. Thus, we can speak of the “visual system” and the “motor system,” each of which has its own distinct circuitry within the brain. At this level of analysis, called systems neuroscience, neuroscientists study how different neural circuits analyze sensory information, form perceptions of the external world, make decisions, and execute movements.
Behavioral Neuroscience. How do neural systems work together to produce integrated behaviors? For example, are different forms of memory accounted for by different systems? Where in the brain do “mind-altering” drugs act, and what is the normal contribution of these systems to the regulation of mood and behavior? What neural systems account for gender-specific behaviors? Where are dreams created and what do they reveal? These questions are studied in behavioral neuroscience.
Cognitive Neuroscience. Perhaps the greatest challenge of neuroscience is understanding the neural mechanisms responsible for the higher levels of human mental activity, such as self-awareness, imagination, and language. Research at this level, called cognitive neuroscience, studies how the activity of the brain creates the mind.
“Neuroscientist” sounds impressive, kind of like “rocket scientist.” But we were all students once, just like you. For whatever reason—maybe we wanted to know why our eyesight was poor, or why a family member suffered a loss of speech after a stroke—we came to share a thirst for knowledge of how the brain works. Perhaps you will, too.
Being a neuroscientist is rewarding, but it does not come easily. Many years of training are required. One may begin by helping out in a research lab during or after college and then going to graduate school to earn a Ph.D. or an M.D. (or both). Several years of post-doctoral training usually follow, learning new techniques or ways of thinking under the direction of an established neuroscientist. Finally, the “young” neuroscientist is ready to set up shop at a university, institute, or hospital.
Broadly speaking, neuroscience research (and neuroscientists) may be divided into three types: clinical, experimental, and theoretical. Clinical research is mainly conducted by physicians (M.D.s). The main medical specialties associated with the human nervous system are neurology, psychiatry, neurosurgery, and neuropathology (Table 1.1). Many who conduct clinical research continue in the tradition of Broca, attempting to deduce from the behavioral effects of brain damage the functions of various parts of the brain. Others conduct studies to assess the benefits and risks of new types of treatment.
Medical Specialists Associated with the Nervous System
An M.D. trained to diagnose and treat diseases of the nervous system
An M.D. trained to diagnose and treat disorders of mood and behavior
An M.D. trained to perform surgery on the brain and spinal cord
An M.D. or Ph.D. trained to recognize the changes in nervous tissue that result from disease
Despite the obvious value of clinical research, the foundation for all medical treatments of the nervous system continues to be laid by experimental neuroscientists, who may hold either an M.D. or a Ph.D. The experimental approaches to studying the brain are so broad that they include almost every conceivable methodology. Neuroscience is highly interdisciplinary; however, expertise in a particular methodology may distinguish one neuroscientist from another. Thus, there are neuroanatomists, who use sophisticated microscopes to trace connections in the brain; neurophysiologists, who use electrodes to measure the brain’s electrical activity; neuropharmacologists, who use drugs to study the chemistry of brain function; molecular neurobiologists, who probe the genetic material of neurons to find clues about the structure of brain molecules; and so on. Table 1.2 lists some of the types of experimental neuroscientists.
Analyzes the development and maturation of the brain
Uses the genetic material of neurons to understand the structure and function of brain molecules
Studies the neural basis of species-specific animal behaviors in natural settings
Examines the effects of drugs on the nervous system
Measures the electrical activity of the nervous system
Physiological psychologist (biological psychologist, psychobiologist)
Theoretical neuroscience is a relatively young discipline, in which researchers use mathematical and computational tools to understand the brain at all levels of analysis. In the tradition of physics, theoretical neuroscientists attempt to make sense of the vast amounts of data generated by experimentalists, with the goals of helping focus experiments on questions of greatest importance and establishing the mathematical principles of nervous system organization.
Neuroscientists of all stripes endeavor to establish truths about the nervous system. Regardless of the level of analysis they choose, they work according to a scientific process consisting of four essential steps: observation, replication, interpretation, and verification.
Observation. Observations are typically made during experiments designed to test a particular hypothesis. For example, Bell hypothesized that the ventral roots contain the nerve fibers that control the muscles. To test this idea, he performed an experiment in which he cut these fibers and then observed whether or not muscular paralysis resulted. Other types of observation derive from carefully watching the world around us, or from introspection, or from human clinical cases. For example, Broca’s careful observations led him to correlate left frontal lobe damage with the loss of the ability to speak.
Replication. Any observation, whether experimental or clinical, must be replicated. Replication simply means repeating the experiment on different subjects or making similar observations in different patients, as many times as necessary to rule out the possibility that the observation occurred by chance.
Interpretation. Once the scientist believes the observation is correct, he or she interprets it. Interpretations depend on the state of knowledge (or ignorance) at the time and on the scientist’s preconceived notions (or “mind set”). Interpretations therefore do not always withstand the test of time. For example, at the time he made his observations, Flourens was unaware that the cerebrum of a bird is fundamentally different from that of a mammal. Thus, he wrongly concluded from experimental ablations in birds that there was no localization of certain functions in the cerebrum of mammals. Moreover, as mentioned before, his profound distaste for Gall surely also colored his interpretation. The point is that the correct interpretation often is not made until long after the original observations. Indeed, major breakthroughs sometimes occur when old observations are reinterpreted in a new light.
Verification. The final step of the scientific process is verification. This step is distinct from the replication the original observer performed. Verification means that the observation is sufficiently robust that any competent scientist who precisely follows the protocols of the original observer can reproduce it. Successful verification generally means that the observation is accepted as fact. However, not all observations can be verified, sometimes because of inaccuracies in the original report or insufficient replication. But failure to verify usually stems from the fact that unrecognized variables, such as temperature or time of day, contributed to the original result. Thus, the process of verification, if affirmative, establishes new scientific fact, or, if negative, suggests new interpretations for the original observation.
Occasionally, one reads in the popular press about a case of scientific fraud. Researchers face keen competition for limited research funds and feel considerable pressure to “publish or perish.” In the interest of expediency, a few have actually published “observations” they in fact never made. Fortunately, such instances of fraud are rare, thanks to the scientific process. Before long, other scientists find they are unable to verify the fraudulent observations and question how they could have been made in the first place. The fact that we can fill this book with so much knowledge about the nervous system stands as a testament to the value of the scientific process.
Most of what we know about the nervous system has come from experiments on animals. In most cases, the animals are killed so their brains can be examined neuroanatomically, neurophysiologically, and/or neurochemically. The fact that animals are sacrificed for the pursuit of human knowledge raises questions about the ethics of animal research.
The Animals. Let’s begin by putting the issue in perspective. Throughout history, humans have considered animals and animal products as renewable natural resources that can be used for food, clothing, transportation, recreation, sport, and companionship. The animals used in research, education, and testing have always been a small fraction of those used for other purposes. For example, in the United States, the number of animals used in all types of biomedical research is very small compared to the number killed for food. The number used specifically in neuroscience research is much smaller still.
Neuroscience experiments are conducted using many different species, ranging from snails to monkeys. The choice of species is generally dictated by the question under investigation, the level of analysis, and the extent to which the knowledge gained can be related to humans. As a rule, the more basic the process under investigation, the more distant can be the evolutionary relationship with humans. Thus, experiments aimed at understanding the molecular basis of nerve impulse conduction can be carried out with a distantly related species, such as the squid. On the other hand, understanding the neural basis of movement and perceptual disorders in humans has required experiments with more closely related species, such as the macaque monkey. Today, more than half of the animals used for neuroscience research are rodents—mice and rats—that are bred specifically for this purpose.
Animal Welfare. In the developed world today, most educated adults have a concern for animal welfare. Neuroscientists share this concern and work to ensure that animals are well treated. Society has not always placed such value on animal welfare, however, as reflected in some of the scientific practices of the past. For example, in his experiments early in the nineteenth century, Magendie used unanesthetized puppies (for which he was later criticized by his scientific rival Bell). Fortunately, heightened awareness of animal welfare has more recently led to significant improvements in how animals are treated in biomedical research.
Today, neuroscientists accept certain moral responsibilities toward their animal subjects:
- Animals are used only in worthwhile experiments that promise to advance our knowledge of the nervous system.
- All necessary steps are taken to minimize pain and distress experienced by the experimental animals (use of anesthetics, analgesics, etc.).
- All possible alternatives to the use of animals are considered.
Adherence to this ethical code is monitored in a number of ways. First, research proposals must pass a review by the Institutional Animal Care and Use Committee (IACUC), as mandated by U.S. federal law. Members of this committee include a veterinarian, scientists in other disciplines, and nonscientist community representatives. After passing the IACUC review, proposals are evaluated for scientific merit by a panel of expert neuroscientists. This step ensures that only the most worthwhile projects are carried out. Then, when neuroscientists submit their observations for publication in the professional journals, the papers are carefully reviewed by other neuroscientists for both scientific merit and animal welfare concerns. Reservations about either issue can lead to rejection of the paper, which in turn can lead to a loss of funding for the research. In addition to these monitoring procedures, federal law sets strict standards for the housing and care of laboratory animals.
Animal Rights. Most people accept the necessity for animal experimentation to advance knowledge, as long as it is performed humanely and with the proper respect for animals’ welfare. However, a vocal and increasingly violent minority seeks the total abolition of animal use for human purposes, including experimentation. These people subscribe to a philosophical position often called animal rights. According to this way of thinking, animals have the same legal and moral rights as humans.
If you are an animal lover, you may be sympathetic to this position. But consider the following questions. Are you willing to deprive yourself and your family of medical procedures that were developed using animals? Is the death of a mouse equivalent to the death of a human being? Is keeping a pet the moral equivalent of slavery? Is eating meat the moral equivalent of murder? Is it unethical to take the life of a pig to save the life of a child? Is controlling the rodent population in the sewers or the roach population in your home morally equivalent to the Holocaust? If your answer is no to any of these questions, then you do not subscribe to the philosophy of animal rights. Animal welfare—a concern that all responsible people share—must not be confused with animal rights.
Animal rights activists have vigorously pursued their agenda against animal research, sometimes with alarming success. They have manipulated public opinion with repeated allegations of cruelty in animal experiments that are grossly distorted or blatantly false. They have vandalized laboratories, destroying years of hard-won scientific data and hundreds of thousands of dollars of equipment (that you, the taxpayer, had paid for). With threats of violence they have driven some researchers out of science altogether.
Fortunately, the tide is turning. Thanks to the efforts of a number of people, scientists and nonscientists alike, the false claims of the extremists have been exposed, and the benefits to humankind of animal research have been extolled (Figure 1.16). Considering the staggering toll in terms of human suffering that results from disorders of the nervous system, neuroscientists take the position that it is our responsibility to wisely use all the resources nature has provided, including animals, to gain an understanding of how the brain functions in health and in disease.
FIGURE 1.16 Our debt to animal research. This poster counters the claims of animal rights activists by raising public awareness of the benefits of animal research. (Source: Foundation for Biomedical Research.)
Modern neuroscience research is expensive, but the cost of ignorance about the brain is far greater. Table 1.3 lists some of the disorders that affect the nervous system. It is likely that your family has felt the impact of one or more of these. Let’s look at a few brain disorders and examine their effects on society.
A progressive degenerative disease of the brain, characterized by dementia and always fatal
A disorder emerging in early childhood characterized by impairments in communication and social interactions, and restricted and repetitive behaviors
A motor disorder caused by damage to the cerebrum before, during, or soon after birth
A serious disorder of mood, characterized by insomnia, loss of appetite, and feelings of dejection
A condition characterized by periodic disturbances of brain electrical activity that can lead to seizures, loss of consciousness, and sensory disturbances
A progressive disease that affects nerve conduction, characterized by episodes of weakness, lack of coordination, and speech disturbance
A progressive disease of the brain that leads to difficulty in initiating voluntary movement
A severe psychotic illness characterized by delusions, hallucinations, and bizarre behavior
A loss of feeling and movement caused by traumatic damage to the spinal cord
A loss of brain function caused by disruption of the blood supply, usually leading to permanent sensory, motor, or cognitive deficit
Alzheimer’s disease and Parkinson’s disease are both characterized by progressive degeneration of specific neurons in the brain. Parkinson’s disease, which results in a crippling impairment of voluntary movement, currently affects over 500,000 Americans.1 Alzheimer’s disease leads to dementia, a state of confusion characterized by the loss of ability to learn new information and to recall previously acquired knowledge. Dementia affects an estimated 18% of people over age 85.2 The number of Americans with dementia totals well over 4 million. Indeed, dementia is now recognized as not an inevitable outcome of aging, as was once believed, but as a sign of brain disease. Alzheimer’s disease progresses mercilessly, robbing its victims first of their mind, then of control over basic bodily functions, and finally of their life; the disease is always fatal. In the United States, the annual cost of care for people with dementia is greater than $100 billion and rising at an alarming rate.
Depression and schizophrenia are disorders of mood and thought. Depression is characterized by overwhelming feelings of dejection, worthlessness, and guilt. Over 30 million Americans will experience a major depressive illness at some time in their lives. Depression is the leading cause of suicide, which claims more than 30,000 lives each year in the United States.3
Schizophrenia is a severe psychiatric disorder characterized by delusions, hallucinations, and bizarre behavior. This disease often strikes at the prime of life—adolescence or early adulthood—and can persist for life. Over 2 million Americans suffer from schizophrenia. The National Institute of Mental Health (NIMH) estimates that mental disorders, such as depression and schizophrenia, cost the United States in excess of $150 billion annually.
Stroke is the fourth leading cause of death in the United States. Stroke victims who do not die, over half a million every year, are likely to be permanently disabled. The annual cost of stroke nationwide is $54 billion.4
Alcohol or drug addiction affects virtually every family in the United States. The cost in terms of treatment, lost wages, and other consequences exceeds $600 billion per year.5
These few examples only scratch the surface. More Americans are hospitalized with neurological and mental disorders than with any other major disease group, including heart disease and cancer.
The economic costs of brain dysfunction are enormous, but they pale in comparison with the staggering emotional toll on victims and their families. The prevention and treatment of brain disorders require an understanding of normal brain function, and this basic understanding is the goal of neuroscience. Neuroscience research has already contributed to the development of increasingly effective treatments for Parkinson’s disease, depression, and schizophrenia. New strategies are being tested to rescue dying neurons in people with Alzheimer’s disease and those who have had a stroke. Major progress has been made in our understanding of how drugs and alcohol affect the brain and how they lead to addictive behavior. The material in this book demonstrates that a lot is known about the function of the brain. But what we know is insignificant compared with what is still left to be learned.
The historical foundations of neuroscience were established by many people over many generations. Men and women today are working at all levels of analysis, using all types of technology, to shed more light on the functions of the brain. The fruits of this labor form the basis for this textbook.
The goal of neuroscience is to understand how nervous systems function. Many important insights can be gained from a vantage point outside the head. Because the brain’s activity is reflected in behavior, careful behavioral measurements inform us of the capabilities and limitations of brain function. Computer models that reproduce the brain’s computational properties can help us understand how these properties might arise. From the scalp, we can measure brain waves, which tell us something about the electrical activity of different parts of the brain during various behavioral states. New computer-assisted imaging techniques enable researchers to examine the structure of the living brain as it sits in the head. And using even more sophisticated imaging methods, we are beginning to see which different parts of the human brain become active under different conditions. But none of these noninvasive methods, old or new, can fully substitute for experimentation with living brain tissue. We cannot make sense of remotely detected signals without being able to see how they are generated and what their significance is. To understand how the brain works, we must open the head and examine what’s inside—neuroanatomically, neurophysiologically, and neurochemically.
The pace of neuroscience research today is truly breathtaking, raising hopes that soon we will have new treatments for the wide range of nervous system disorders that debilitate and cripple millions of people annually. However, despite the progress in recent decades and the centuries preceding them, we still have a long way to go before we fully understand how the brain performs all of its amazing feats. But this is the fun of being a neuroscientist: Because our ignorance of brain function is so vast, a startling new discovery lurks around virtually every corner.
1. What are brain ventricles, and what functions have been ascribed to them over the ages?
2. What experiment did Bell perform to show that the nerves of the body contain a mixture of sensory and motor fibers?
3. What did Flourens’ experiments suggest were the functions of the cerebrum and the cerebellum?
5. A region of the cerebrum is now called Broca’s area. What function do you think this region performs, and why?
6. What are the different levels of analysis in neuroscience research? What questions do researchers ask at each level?
7. What are the steps in the scientific process? Describe each one.
Allman JM. 1999. Evolving Brains. New York: Scientific American Library.
Clarke E, O’Malley C. 1968. The Human Brain and Spinal Cord, 2nd ed. Los Angeles: University of California Press.
Corsi P, ed. 1991. The Enchanted Loom. New York: Oxford University Press.
Crick F. 1994. The Astonishing Hypothesis: The Scientific Search for the Soul. New York: Macmillan.
Finger S. 1994. Origins of Neuroscience. New York: Oxford University Press.
Glickstein M. 2014. Neuroscience: A Historical Introduction. Cambridge, MA: MIT Press.
1National Institute of Neurological Disorders and Stroke. “Parkinson Disease Backgrounder.” October 18, 2004.
2U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality. “Approximately 5 Percent of Seniors Report One or More Cognitive Disorders.” March 2011.
3National Institute of Mental Health. “Suicide in the U.S.: Statistics and Prevention.” September 27, 2010.
4American Heart Association /American Stroke Association. “Impact of Stroke (Stroke Statistics).” May 1, 2012.
5National Institutes of Health, National Institute of Drug Abuse. “DrugFacts: Understanding Drug Abuse and Addiction.” March 2011.
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