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The brain is the center of the nervous system in animals. All vertebrates, and the majority of invertebrates, have a brain. Some "primitive" animals such as jellyfishes and starfishes have a decentralized nervous system without a brain, while sponges lack any nervous system at all. In vertebrates, the brain is located in the head, protected by the skull and close to the primary sensory apparatus of vision, hearing, balance, taste, and smell.

Brains can be extremely complex. The human brain contains roughly 100 billion neurons, linked with up to 10,000 synaptic connections each. These neurons communicate with one another by means of long protoplasmic fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body and target them to specific recipient cells. Charles Sherrington, a pioneering investigator of brain function, visualized the workings of the brain in action in poetic terms:

The great topmost sheet of the mass, that where hardly a light had twinkled or moved, becomes now a sparkling field of rhythmic flashing points with trains of traveling sparks hurrying hither and thither. The brain is waking and with it the mind is returning. It is as if the Milky Way entered upon some cosmic dance. Swiftly the head mass becomes an enchanted loom where millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern though never an abiding one; a shifting harmony of subpatterns.
— C. S. Sherrington, ^[1]

From a philosophical point of view, it might be said that the most important function of the brain is to serve as the physical structure underlying the mind. From a biological point of view, though, the most important function is to generate behaviors that promote the welfare of an animal. Brains control behavior either by activating muscles, or by causing secretion of chemicals such as hormones. Not all behaviors require a brain. Even single-celled organisms may be capable of extracting information from the environment and acting in response to it.^[2] Sponges, which lack a central nervous system, are capable of coordinated body contractions and even locomotion.^[3] In vertebrates, the spinal cord by itself contains neural circuitry capable of generating reflex responses as well as simple motor patterns such as swimming or walking.^[4] However, sophisticated control of behavior on the basis of complex sensory input requires the information-integrating capabilities of a centralized brain.

In spite of rapid scientific progress, the way that brains work remains in many respects a mystery. The operations of individual neurons and synapses are now understood in considerable detail, but the way they cooperate in ensembles of thousands or millions has been very difficult to decipher. Methods of observation such as EEG recording and functional brain imaging tell us that brain operations are highly organized, but these methods do not have enough resolution to reveal the activity of individual neurons. Thus, even the most fundamental principles of neural network computation may to a large extent remain for future investigators to discover.^[5]

This article examines the brains of all types of animals, including humans, in a comparative way: it deals with the human brain to the extent that it shares properties with the brains of other species. For an account of features that only apply to humans, see the human brain article.

Structure of the brain

General anatomy

File:ComparitiveBrainSize.jpg

Brains of 8 species of mammals

The human brain weighs about three pounds, or 1.5 kg.^[6]^[7] In its natural state it is very soft, having approximately the consistency of pudding, although surrounded by leathery membranes. When alive it is pinkish on the outside, and mostly white on the inside, with subtle variations in color. The brains of other species have generally similar properties, but smaller sizes in relation to the body.

The largest part of the human brain is the cerebral hemispheres, situated at the top and covered with a convoluted cortex.^[8] Underneath the cerebrum lies the brainstem, appearing somewhat like a stalk on which the cerebrum is attached. At the back of the brain, beneath the cerebrum and behind the brainstem, is the cerebellum, a structure with a horizontally furrowed surface that makes it look different from any other brain area. In other mammals, the same structures are present, but the cerebrum is not so large in relation to the brain as a whole. As a rule, the smaller the cerebrum, the less convoluted the cortex. The cortex of a rat or mouse is almost completely smooth. The cortex of a dolphin or whale, on the other hand, is more convoluted than the cortex of a human.

In vertebrates, the brain is surrounded by connective tissues called meninges, a system of membranes that separate the skull from the brain.^[7] This three-layered covering is composed of (from the outside in) the dura mater ("hard mother"), arachnoid mater ("spidery mother"), and pia mater ("soft mother"). The arachnoid and pia are physically connected and thus often considered as a single layer, the pia-arachnoid. Below the arachnoid is the subarachnoid space which contains cerebrospinal fluid (CSF), which circulates in the narrow spaces between cells and through cavities called ventricles, and serves to nourish, support, and protect the brain tissue. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood-brain barrier which protects the brain from toxins that might enter through the blood.

The cortex is the part of the brain that most strongly distinguishes mammals from other vertebrates, primates from other mammals, and humans from other primates. In non-mammalian vertebrates, the surface of the cerebrum is lined with a comparatively simple layered structure called the pallium.^[9] In mammals, the pallium evolves into a complex 6-layered structure called neocortex. In primates, the neocortex is greatly enlarged in comparison to its size in non-primates, especially the part called the frontal lobes. In humans, this enlargement of the frontal lobes is taken to an extreme, and other parts of the cortex also become quite large and complex.

Principles of brain architecture

Central nervous systems of a medical leech and a human, illustrating similarity of overall form.

The brain is the most complex biological structure known to us,^[10] and comparing the brains of different species on the basis of overt appearance is often difficult. Nevertheless there are common principles of brain architecture that apply across a very wide range of species. These are revealed mainly by three approaches: evolution, development, and genetics. The evolutionary approach means comparing brain structures of different species, and using the principle that features found in all branches that descend from a given ancient form were probably present in the ancestor as well. The developmental approach means examining how the form of the brain changes during the progression from embyronic to adult stages. The genetic approach means analyzing gene expression in various parts of the brain across a range of species. Each approach complements and informs the other two.

Body plan of a generic bilaterian animal. The nervous system has the form of a nerve cord with segmental enlargements, and a "brain" at the front.

With the exception of a few primitive forms such as sponges and jellyfish, all of the animals on earth today are bilaterians, meaning animals with a bilaterally symmetric body shape (that is, left and right sides that are approximate mirror images of each other). Paleontologists believe that all bilaterians descend from a common ancestor that appeared early in the Cambrian period, 550-600 million years ago.^[11] This ancestor had the shape of a simple tube worm with a segmented body, and at an abstract level, that worm-shape continues to be reflected in the body and nervous system plans of all modern bilaterians, including humans.^[12] The fundamental bilaterian body form is a tube with a hollow gut cavity running from mouth to anus, and a nerve cord with an enlargement (a "ganglion") for each body segment, with an especially large ganglion at the front, called the "brain".

Invertebrates

In many invertebrates—insects, molluscs, worms of many types, etc.—the components of the brain, and their arrangement, differ so greatly from the vertebrate pattern that it is hard to make meaningful comparisons except on the basis of genetics. Two groups of invertebrates have notably complex brains: arthropods (insects, crustaceans, arachnids, and others), and cephalopods (octopuses, squids, and similar molluscs).^[13] The brains of arthropods and cephalopods arise from twin parallel nerve cords that extend through the body of the animal. Arthropods have a central brain with three divisions and large optical lobes behind each eye for visual processing.^[13] Cephalopods have the largest brains of any invertebrates. The brain of the octopus in particular is highly developed, comparable in complexity to the brains of some vertebrates.

There are a few invertebrates whose brains have been studied intensively. The large sea slug aplysia was chosen by Nobel Prize-winning neurophysiologist Eric Kandel, because of the simplicity and accessibility of its nervous system, as a model for studying the cellular basis of learning and memory, and subjected to hundreds of experiments.^[14] The most thoroughly studied invertebrate brains, however, belong to the fruit fly drosophila and the tiny roundworm Caenorhabditis elegans.

Because of the large array of techniques available for studying their genetics, fruit flies have been a natural subject for studying the role of genes in brain development.^[15] Remarkably, many aspects of drosophila neurogenetics have turned out to be relevant to humans. The first biological clock genes, for example, were identified by examining drosophila mutants that showed disrupted daily activity cycles.^[16] A search in the genomes of vertebrates turned up a set of analogous genes, which were found to play similar roles in the mouse biological clock—and therefore almost certainly in the human biological clock as well.^[17]

Like drosophila, c. elegans has been studied largely because of its importance in genetics.^[18] In the early 1970s, Sydney Brenner chose it as a model system for studying the way that genes control development. One of the advantages of working with this worm is that the body plan is very stereotyped: the nervous system of the hermaphrodite morph contains exactly 302 neurons, always in the same places, making identical synaptic connections in every worm.^[19] In a heroic project, Brenner's team sliced worms into thousands of ultrathin sections and photographed every section under an electron microscope, then visually matched fibers from section to section, in order to map out every neuron and synapse in the entire body.^[20] Nothing approaching this level of detail is available for any other organism, and the information has been used to enable a multitude of studies that would not have been possible without it.

Vertebrates

The first vertebrates appeared over 500 million years ago (Mya), during the Cambrian period, and may have somewhat resembled the modern hagfish in form. Sharks appeared about 450 Mya, amphibians about 400 Mya, reptiles about 350 Mya, and mammals about 200 Mya. It is dangerous to describe any modern species as more "primitive" than others, since all have an equally long evolutionary history, but the brains of modern hagfishes, lampreys, sharks, amphibians, reptiles, and mammals show a gradient of size and complexity that roughly follows the evolutionary sequence.^[21] All of these brains contain the same set of basic anatomical components, but many are rudimentary in hagfishes, whereas in mammals the foremost parts are greatly elaborated and expanded.

Diagram depicting the main subdivisions of the embryonic vertebrate brain. These regions will later differentiate into forebrain, midbrain and hindbrain structures.

All vertebrate brains share a common underlying form, which can most easily be appreciated by examining how they develop.^[22] The first appearance of the nervous system is as a thin strip of tissue running along the back of the embryo. This strip thickens and then folds up to form a hollow tube. The front end of the tube develops into the brain. In its earliest form, the brain appears as three swellings, which eventually become the forebrain, midbrain, and hindbrain. In many classes of vertebrates these three parts remain similar in size in the adult, but in mammals the forebrain becomes much larger than the other parts, and the midbrain quite small.

Main anatomical regions of the vertebrate brain.

Neuroanatomists usually consider the brain to consist of six main regions: the telencephalon (cerebral hemispheres), diencephalon (thalamus and hypothalamus), mesencephalon (midbrain), cerebellum, pons, and medulla.^[23] Each of these areas in turn has a complex internal structure. Some areas, such as the cortex and cerebellum, consist of layers, folded or convoluted to fit within the available space. Other areas consist of clusters of many small nuclei. If fine distinctions are made on the basis of neural structure, chemistry, and connectivity, thousands of distinguishable areas can be identified within the vertebrate brain.

Some branches of vertebrate evolution have led to substantial changes in brain shape, especially in the forebrain. The brain of a shark shows the basic components in a straighforward way, but in teleost fishes (the great majority of modern species), the forebrain has become "everted", like a sock turned inside out. In birds, also, there are major changes in shape.^[24] One of the main structures in the avian forebrain, the dorsal ventricular ridge, was long thought to correspond to the basal ganglia of mammals, but is now thought to be more closely related to the neocortex.^[25]

Crude sketch of the approximate locations of several important parts of the vertebrate brain, on the outline of a shark brain.

Areas of the vertebrate brain and their functions

Several brain areas have maintained their identities across the whole range of vertebrates, from hagfishes to humans. Here is a list of some of the most important areas, along with a very brief description of their functions as currently understood (but note that the functions of most of them are still disputed to some degree):

The medulla, along with the spinal cord, contains many small nuclei involved in a wide variety of sensory and motor functions.
The hypothalamus is a small region at the base of the forebrain, whose complexity and importance belies its size. It is composed of numerous small nuclei, each with distinct connections and distinct neurochemistry. The hypothalamus is the central control station for sleep/wake cycles, control of eating and drinking, control of hormone release, and many other critical biological functions.^[26]
Like the hypothalamus, the thalamus is a collection of nuclei with diverse functions. Some of them are involved in relaying information to and from the cerebral hemispheres. Others are are involved in motivation. The subthalamic area (zona incerta) seems to contain action-generating systems for several types of "consummatory" behaviors, including eating, drinking, defecation, and copulation.^[27]
The cerebellum modulates the outputs of other brain systems to make them more precise. Removal of the cerebellum does not prevent an animal from doing anything in particular, but it makes actions hesitant and clumsy. This precision is not built-in, but learned by trial and error. Learning how to ride a bicycle is an example of a type of neural plasticity that may take place largely within the cerebellum.^[28]
The tectum, often called "optic tectum", allows actions to be directed toward points in space. In mammals it is called the "superior colliculus", and its best studied function is to direct eye movements. It also directs reaching movements, though. It gets strong visual inputs, but also inputs from other senses that are useful in directing actions, such as auditory input in owls, input from the thermosensitive pit organs in snakes, etc. In amphibians, it is the largest part of the brain.^[29]
The pallium is a layer of gray matter that lies on the surface of the forebrain. In reptiles and mammals it is called cortex instead. The pallium is involved in multiple functions, including olfaction and spatial memory. In mammals, where it comes it dominate the brain, it subsumes functions from many subcortical areas.^[30]
The hippocampus, strictly speaking, is found only in mammals. However, the area it derives from, the medial pallium, has counterparts in all vertebrates. There is evidence that this part of the brain is involved in spatial memory and navigation in fishes, birds, reptiles, and mammals.^[31]
The basal ganglia are a group of interconnected structures in the forebrain, of which our understanding has increased enormously over the last few years. The primary function of the basal ganglia seems to be action selection. They send inhibitory signals to all parts of the brain that can generate actions, and in the right circumstances can release the inhbition, so that the action-generating systems are able to execute their actions. Rewards and punishments exert their most important neural effects within the basal ganglia.^[32]
The olfactory bulb is a special structure that processes olfactory sensory signals, and sends its output to the olfactory part of the pallium. It is a major brain component in many vertebrates, but much reduced in primates.

Mammals

Increase in relative size of the cerebral hemispheres (shaded) in the evolutionary progression leading to primates.

The hindbrain and midbrain of mammals are generally similar to those of other vertebrates, but dramatic differences appear in the forebrain, which is not only greatly enlarged, but also altered in structure. In mammals, the surface of the cerebral hemispheres is mostly covered with 6-layered isocortex, more complex than the 3-layered pallium seen in most vertebrates. Also the hippocampus of mammals has a distinctive structure.

Unfortunately, the evolutionary history of these mammalian features is difficult to work out. This is largely because of a "missing link" problem. The ancestors of mammals, called synapsids, split off from the ancestors of modern reptiles and birds about 350 million years ago. However, the most recent branching that has left living results within the mammals was the split between monotremes (the platypus and echidna), marsupials (opossum, kangaroo, etc.) and placentals (most living mammals), which took place about 120 million years ago. The brains of monotremes and marsupials are distinctive from those of placentals in some ways, but they have fully mammalian cortical and hippocampal structures. Thus, these structures must have evolved during the "Dark Ages" between 350 and 120 million years ago, a period for which we have no evidence except fossils—but fossils never preserve tissue as soft as brain.

Primates, including humans

The primate brain contains the same structures as the brains of other mammals, but is considerably larger in proportion to body size. Most of the enlargement comes from a massive expansion of the cortex, focusing especially on the parts subserving vision and forethought. The visual processing network of primates is very complex, including at least 30 distinguishable areas, with a bewildering web of interconnections. Taking all of these together, visual processing makes use of about half of the brain. The other part of the brain that is greatly enlarged is the prefrontal cortex, whose functions are difficult to summarize succinctly, but relate to planning, working memory, motivation, attention, and executive control.

Brain size and its significance

There has been quite a bit of study of the relationships between brain size, body size, and other variables across a wide range of species. The reason why all this data exists is probably obvious: the easiest thing to do with any object is to weigh it. Even for extinct species brain size can be estimated by measuring the cavity inside the skull. However, just because data is easy to obtain does not mean that it is easy to understand. There are a few systematic relationships, but their functional significance is far from clear.

As might be expected, brain size tends to increase with body size (measured by weight, which is roughly equivalent to volume). The relationship is not a strict proportionality, though: averaging across all orders of mammals, it follows a power law, with an exponent of about 0.75.^[33] There are good reasons for expecting a power law: for example, the body-size-to-body-length relationship follows a power law with an exponent of 0.33, and the body-size-to-surface-area relationship a power law with an exponent of 0.67. The explanation for an exponent of 0.75 is not obvious, though—however it is worth noting that several physiological variables appear to be related to body size by approximately the same exponent, for example, the basal metabolic rate.^[34]

The formula applies to the "average" brain of mammals taken as a whole, but each family (cats, rodents, primates, etc) departs from it to some degree, in a way that generally reflects the overall "sophistication" of behavior.^[35] Primates, for a given body size, have brains 5 to 10 times as large as the formula predicts. Predators tend to have relatively larger brains than the animals they prey on; placental mammals (the great majority) have relatively larger brains than marsupials such as the opossum.

When the mammalian brain increases in size, not all parts increase at the same rate.^[36] In particular, the larger the brain of a species, the greater the fraction taken up by the cortex. Thus, in the species with the largest brains, most of their volume is filled with cortex: this applies not only to humans, but also to animals such as dolphins, whales, or elephants.

The evolution of homo sapiens over the past two million years has been marked by a steady increase in brain size, but much of it can be accounted for by corresponding increases in body size.^[37] There are, however, many departures from the trend that are difficult to explain in a systematic way: in particular, the appearance of modern man about 100,000 years ago was marked by a decrease in body size at the same time as an increase in brain size. Even so, it is notorious that Neanderthals, which went extinct about 40,000 years ago, had larger brains than modern homo sapiens.^[38]

Not all investigators are happy with the amount of attention that has been paid to brain size. Roth and Dicke, for example, have argued that factors other than size are more highly correlated with intelligence, such as the number of cortical neurons and the speed of their connections.^[39] Moreover they point out that intelligence depends not just on the amount of brain tissue, but on the details of how it is structured.

Microscopic structure

The brain is composed of two broad classes of cells, neurons and glia. Neurons receive more attention, but glial cells actually outnumber them by about 10 to 1. Glia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development.

The property that makes neurons so important is that, unlike glia, they are capable of sending signals to each other over long distances. They send these signals by means of an axon, a thin protoplasmic fiber that extends from the cell body and projects, usually with numerous branches, to other areas, sometimes nearby, sometimes in distant parts of the brain or body. The extent of an axon can be extraordinary: to take an example, if a pyramidal cell of the neocortex were magnified so that its cell body became the size of a human, its axon, equally magnified, would become a cable a few inches in diameter, extending farther than a mile. These axons transmit signals in the form of electrochemical pulses called action potentials, lasting less than a thousandth of a second and traveling along the axon at speeds of 0.1-100 meters per second. Some neurons emit action potentials constantly, at rates of 10-100 per second, usually in irregular temporal patterns; other neurons are quiet most of the time, but occasionally emit a burst of action potentials.

Axons transmit signals to other neurons, or to non-neuronal cells, by means of specialized junctions called synapses. A single axon may make as many as several thousand synaptic connections. When an action potential, traveling along an axon, arrives at a synapse, it causes a chemical called a neurotransmitter to be released. The neurotransmitter binds to receptor molecules in the membrane of the target cell. Some types of neuronal receptors are excitatory, meaning that they increase the rate of action potentials in the target cell; other receptors are inhibitory, meaning that they decrease the rate of action potentials; others have complex modulatory effects on the target cell.

Nissl-stained cross section of Chlorocebus monkey brain. Source: brainmaps.org

Axons actually fill most of the space in the brain. Often large groups of them travel together in bundles called "nerve fiber tracts". In many cases, each axon is wrapped in a thick sheath of a fatty substance called myelin, which serves to greatly increase the speed of action potential propagation. Myelin is white in color, so parts of the brain filled exclusively with nerve fibers appear as "white matter", in contrast to the "gray matter" that marks areas where high densities of neuron cell bodies are located. The illustration on the right shows a thin section of one hemisphere of the brain of a Chlorocebus monkey, stained using a Nissl stain, which colors the nuclei of neurons. This makes the gray matter show up as a dark blue, and the white matter show up as a paler blue. Several important forebrain structures, including the cortex, can easily be identified in brain sections that are stained in this way. Neuroanatomists have invented hundreds of stains that color different types of neurons, or different types of brain tissue, in distinct ways: the Nissl stain shown here is probably the most widely used.

Development

The brain does not simply grow; it develops in an intricately orchestrated sequence of steps.^[40] Many neurons are created in special zones that contain stem cells, and then migrate through the tissue to reach their ultimate locations.^[41] In the cortex, for example, the first stage of development is the formation of a "scaffold" by a special group of glial cells, called radial glia, which send fibers vertically across the cortex. New cortical neurons are created at the bottom of the cortex, and then "climb" along the radial fibers until they reach the layers they are destined to occupy in the adult.

Once a neuron is in place, it begins to extend dendrites and an axon into the area around it.^[42] Axons, because they commonly extend a great distance from the cell body and need to make contact with specific targets, grow in a particularly complex way. The tip of a growing axon consists of a blob of protoplasm called a "growth cone", studded with chemical receptors. These receptors sense the local environment, causing the growth cone to be attracted or repelled by various cellular elements, and thus to be pulled in a particular direction at each point along its path. The result of this pathfinding process is that the growth cone navigates through the brain until it reaches its destination area, where other chemical cues cause it to begin generating synapses. Taking the entire brain into account, many thousands of genes give rise to proteins that influence axonal pathfinding.

The synaptic network that finally emerges is only partly determined by genes, though. In many parts of the brain, axons initially "overgrow", and then are "pruned" by mechanisms that depend on neural activity.^[43] In the projection from the eye to the midbrain, for example, the structure in the adult contains a very precise mapping, connecting each point on the surface of the retina to a corresponding point in a midbrain layer. In the first stages of development, each axon from the retina is guided to the right general vicinity in the midbrain by chemical cues, but then branches very profusely and makes initial contact with a wide swath of midbrain neurons. The retina, before birth, contains special mechanisms that cause it to generate waves of activity that originate spontaneously at some point and then propagate slowly across the retinal layer.^[44] These waves are useful because they cause neighboring neurons to be active at the same time: that is, they produce a neural activity pattern that contains information about the spatial arrangement of the neurons. This information is exploited in the midbrain by a mechanism that causes synapses to weaken, and eventually vanish, if activity in an axon is not followed by activity of the target cell. The result of this sophisticated process is a gradual tuning and tightening of the map, leaving it finally in its precise adult form.

Similar things happen in other brain areas: an initial synaptic matrix is generated as a result of genetically determined chemical guidance, but then gradually refined by activity-dependent mechanisms, partly driven by internal dynamics, partly by external sensory inputs. In some cases, as with the retina-midbrain system, activity patterns depend on mechanism that operate only in the developing brain, and apparently exist solely for the purpose of guiding development.

In humans, and many other mammals, new neurons are created mainly before birth. In humans, the infant brain actually contains substantially more neurons than the adult brain.^[45] There are, however, a few areas where new neurons continue to be generated throughout life. The two areas for which this is well established are the olfactory bulb, which is involved in the sense of smell, and the dentate gyrus of the hippocampus, where there is evidence that the new neurons play a role in storing newly acquired memories. With these exceptions, however, the set of neurons that are present in early childhood is the set that are present for life. (Glial cells are different: as with most types of cells in the body, these are generated throughout the lifespan.)

Although the pool of neurons is largely in place by birth, their axonal connections continue to develop for years afterward. In particular, in humans full myelination is not completed until the age of 5 or 6.

Nature versus nurture

There has long been debate about whether the qualities of mind, personality, and intelligence can mainly be attributed to heredity or to upbringing.^[46] This is not just a philosophical question: it has great practical relevance to parents and educators. Although many details remain to be settled, neuroscience clearly shows that both factors are essential. Genes determine the general form of the brain, and genes determine how the brain reacts to experience. Experience, however, is required to refine the matrix of synaptic connections. In some respects it is mainly a matter of presence or absence of experience during critical periods of development.^[47] In other respects, the quantity and quality of experience may be more relevant: for example, there is substantial evidence that animals raised in enriched environments have thicker cortices (indicating a higher density of synaptic connections) than animals whose levels of stimulation are restricted.^[48]

Functions of the brain

Vertebrate brains receive signals through nerves arriving from sensory systems. These signals are then processed throughout the central nervous system; reactions are formulated based upon reflex and learned experiences. A similarly extensive nerve network delivers signals from the brain to muscles throughout the body. Anatomically, the majority of afferent (incoming) and efferent (outgoing) nerves are connected to the spinal cord, which then transfers the signals to and from the brain. There are also, however, several cranial nerves that connect parts of the body directly to the brain.

Sensory input is processed by the brain to recognize danger, find food, identify potential mates, and perform more sophisticated functions. Visual, touch, and auditory sensory pathways of vertebrates are routed to specific nuclei of the thalamus and then to regions of the cerebral cortex that are specific to each sensory system, the visual system, the auditory system, and the somatosensory system. Olfactory pathways are routed to the olfactory bulb, then to various parts of the olfactory system. Taste is routed through the brainstem and then to other portions of the gustatory system.

To control movement the brain has several parallel systems of muscle control. The motor system controls voluntary muscle movement, aided by the motor cortex, cerebellum, and the basal ganglia. The system eventually projects to the spinal cord and then out to the muscle effectors. Nuclei in the brain stem control many involuntary muscle functions such as heart rate and breathing. In addition, many automatic acts (simple reflexes, locomotion) can be controlled by the spinal cord alone.

Feedforward versus feedback processing

Comparison of signal flow within the brain for an eye movement driven by detection of a change in the visual scene (left), versus an eye movement driven by internal brain dynamics (i.e., "thought"). The final stages are the same, but the early stages of the internally generated movement involve feedback signal flow between multiple cortical areas.

It is useful to distinguish between two ways of thinking about how the brain generates behavior. In the "feedforward mode", signals originating from sensory inputs are propagated through the brain until they ultimately reach motor output areas. In the "feedback mode", signals are generated within the brain by ongoing dynamic activity, and influence behaviors in ways that are not immediately caused by sensory inputs. As an example, consider the neural processing involved in two somewhat similar behaviors: first, an eye movement directed toward an object that has unexpectedly moved; second, an eye movement directed toward an object that has just entered our thoughts.

In the first case, the neural processing sequence begins with photoreceptors in the retina, which send axons to the visual part of the thalamus, among other places. We can trace the resulting brain activation through a series of areas: the primary visual cortex, secondary visual cortex, motion-detecting visual cortex (area MT), frontal eye fields, superior colliculus, and ultimately the oculomotor nuclei of the brainstem, which are capable of directly activating the muscles that move the eyes. There are also a number of side-paths that modulate the response, but this is probably the primary circuit.

In the second case, no clear beginning can be identified: instead, neural activity patterns circulating among several cortical areas, including the prefrontal cortex, parietal areas involved in attention, temporal areas involved in memory and object recognition, and occipital areas directly involved in vision, all combine at some moment to produce activation in an "executive" part of the prefrontal cortex. From this point, the sequence overlaps with the other: the prefrontal cortex activates the frontal eye fields, superior colliculus, etc.

On the whole, neuroscientists understand feedforward processing considerably better than feedback processing. This is largely a result of experimental convenience: it is much easier to study a process if an experimenter has control over the event that triggers it. Nevertheless, both anatomical and functional considerations indicate that feedback signal flow is at least as important as feedforward flow. The great majority of connections in the brain, especially in the cerebral cortex, are reciprocal, and in many cases feedback connections are numerically dominant. In fact, neural connections that can be identified with feedforward signal processing pathways only make up a small fraction of the connections in the brain.

Brain systems

The brain can be divided into subsystems in a number of ways: anatomically (as described above), chemically, and functionally.

Neurotransmitter systems

With few exceptions, each neuron in the brain releases the same neurotransmitter, or set of neurotransmitters, at all of the synaptic connections it makes with other neurons.^[49] Thus, a neuron can be characterized by the neurotransmitters it releases. The two neurotransmitters that appear most frequently are glutamate (which is almost always excitatory), and GABA (which is almost always inhibitory). Neurons using these transmitters can be found in nearly every part of the brain. In fact, they combine numerically to make up more than 99% of the brain's entire pool of synapses.

This does not mean that other neurotransmitters are unimportant, though. The great majority of psychoactive drugs exert their effects by altering neurotransmitter systems, and only a small proportion of them act directly on glutamatergic or GABAergic transmission. Drugs such as caffeine, nicotine, heroin, cocaine, Prozac, Thorazine, etc., etc. act on other neurotransmitters. Many of these other transmitters come from neurons that are localized in particular parts of the brain. Serotonin, for example—the primary target of antidepressant drugs and many dietary aids—comes exclusively from a small brainstem area called the Raphe nuclei. Norepinephrine, which is involved in arousal, comes exclusively from a nearby small area called the locus ceruleus. Histamine, as a neurotransmitter, comes from a tiny part of the hypothalamus called the tuberomammilary nucleus (histamine also has non-CNS functions, but the neurotransmitter function is what causes antihistamines to have sedative effects). Other neurotransmitters such as acetylcholine and dopamine have multiple sources in the brain, but are not as ubiquitously distributed as glutamate and GABA.

Sensory systems

One of the primary functions of a brain is to extract biologically relevant information from sensory inputs. Even in the human brain, sensory processes go well beyond the classical five senses of sight, sound, taste, touch, and smell: our brains are provided with information about temperature, balance, limb position, and the chemical composition of the bloodstream, among other things. All of these modalities are detected by specialized sensors that project signals into the brain. In non-humans, additional senses may be present, such as the infrared heat-sensors in the pit organs of snakes; or the "standard" senses may be used in nonstandard ways, as in the auditory "sonar" of bats.

Every sensory system has idiosyncrasies, but here is a list of a few general principles, using the sense of hearing for examples:

Each system begins with specialized "sensory receptor" cells. These are neurons, but unlike most neurons, they are not controlled by synaptic input from other neurons: instead they are activated by membrane-bound receptors that are sensitive to some physical modality, such as light, temperature, or physical stretching. The axons of sensory receptor cells travel into the spinal cord or brain. For the sense of hearing, the receptors are located in the inner ear, on the cochlea, and are activated by vibration.
For most senses, there is a "primary nucleus" or set of nuclei, located in the brainstem, that gathers signals from the sensory receptor cells. For the sense of hearing, these are the cochlear nuclei.
In many cases, there are secondary subcortical areas that extra special information of some sort. For the sense of hearing, the superior olivary area and inferior colliculus are involved in comparing the signals from the two ears to extract information about the direction of the sound source, among other functions.
Each sensory system also has a special part of the thalamus dedicated to it, which serves as a relay to the cortex. For the sense of hearing, this is the medial geniculate nucleus.
For each sensory system, there is a "primary" cortical area that receives direct input from the thalamic relay area. For the auditory system this is A1, located in the upper part of the temporal lobe.
There are also usually a set of "higher level" cortical sensory areas, which analyze the sensory input in specific ways. For the auditory system, there are areas that analyze sound quality, rhythm, and temporal patterns of change, among other features.
Finally, there are multimodal areas that combine inputs from different sensory modalities, for example auditory and visual. At this point, the signals have reached parts of the brain that are best described as integrative rather than specifically sensory.

All of these rules have exceptions, for example: (1) For the sense of touch (which is actually a set of at least half-a-dozen distinct mechanical senses), the sensory inputs terminate mainly in the spinal cord, on neurons that then project to the brainstem. (2) For the sense of smell, there is no relay in the thalamus; instead the signals go directly from the primary brain area—the olfactory bulb—to the cortex.

Motor systems

Motor systems are areas of the brain that are more or less directly involved in producing body movements, that is, in activating muscles. With the exception of the muscles that control the eye, all of the "voluntary" muscles^[50] in the body are directly innervated by motor neurons in the spinal cord, which therefore are the "final common path" for the movement-generating system. Spinal motor neurons are controlled both by neural circuits intrinsic to the spinal cord, and by inputs that descend from the brain. The intrinsic spinal circuits implement many reflex responses, and also contain pattern generators for rhythmic movements such as walking or swimming. The descending connections from the brain allow for more sophisticated control.

The brain contains a number of areas that project directly to the spinal cord. At the lowest level are motor areas in the medulla and pons. At a higher level are areas in the midbrain, such as the red nucleus, which is responsible for coordinating movements of the arms and legs. At a higher level yet is the primary motor cortex, a strip of tissue located at the posterior edge of the frontal lobe. The primary motor cortex sends projections to the subcortical motor areas, but also sends a massive projection directly to the spinal cord, via the so-called pyramidal tract. This direct corticospinal projection allows for precise voluntary control of the fine details of movements.

Other "secondary" motor-related brain areas do not project directly to the spinal cord, but instead act on the cortical or subcortical primary motor areas. Among the most important secondary areas are the premotor cortex, basal ganglia, and cerebellum:

The premotor cortex (which is actually a large complex of areas) adjoins the primary motor cortex, and projects to it. Whereas elements of the primary motor cortex map to specific body areas, elements of the premotor cortex are often involved in coordinated movements of multiple body parts.
The basal ganglia are a set of structures in the base of the forebrain that project to many other motor-related areas. Their function has been difficult to understand, but the most popular theory currently is that they play a key role in action selection. Most of the time they restrain actions by sending constant inhibitory signals to action-generating systems, but in the right circumstances, they release this inhibition and therefore allow their targets to take control of behavior.
The cerebellum is a very distinctive structure attached to the back of the brain. It does not control or originate behaviors, but instead generates corrective signals to make movements more precise. People with cerebellar damage are not paralyzed in any way, but their body movements become erratic and uncoordinated.

In addition to all of the above, the brain and spinal cord contain extensive circuitry to control the autonomic nervous system, which works by secreting hormones and by modulating the "smooth" muscles of the gut. The autonomic nervous system affects heart rate, digestion, respiration rate, salivation, perspiration, urination, and sexual arousal—but most of its functions are not under direct voluntary control.

Arousal systems

Perhaps the most obvious aspect of the behavior of any animal is the daily cycle between sleeping and waking. Arousal and alertness are also modulated on a finer time scale, though, by an extensive network of brain areas.

A key component of the arousal system is the suprachiasmatic nucleus (SCN), a tiny part of the hypothalamus located directly above the point at which the optic nerves from the two eyes cross. The SCN contains the body's central biological clock. Neurons there show activity levels that rise and fall with a period of about 24 hours: these activity fluctuations are driven by rhythmic changes in expression of a set of "clock genes". The SCN continues to keep time even if it is excised from the brain and placed in a dish of warm nutrient solution, but it ordinarily receives input from the optic nerves that allow daily light-dark cycles to calibrate the clock.

The SCN projects to a set of areas in the hypothalamus, brainstem, and midbrain that are involved in implementing sleep-wake cycles. An important component of the system is the so-called reticular formation, a group of neuron-clusters scattered diffusely through the core of the lower brain. Reticular neurons send signals to the thalamus, which in turn sends activity-level-controlling signals to every part of the cortex. Damage to the reticular formation can produce a permanent state of coma.

Sleep involves great changes in brain activity. Until the 1950s it was generally believed that the brain essentially shuts off during sleep, but this is now known to be far from true: activity continues, but the pattern becomes very different. In fact, there are two types of sleep, slow wave sleep (non-dreaming) and REM sleep (dreaming), each with its own distinct brain activity pattern. During slow wave sleep, activity in the cortex takes the form of large synchronized waves, where in the waking state it is noisy and desynchronized. Levels of the neurotransmitters norepinephrine and serotonin drop during slow wave sleep, and fall almost to zero during REM sleep; levels of acetylcholine show the reverse pattern.

PET Image of the human brain showing energy consumption

Brain energy consumption

Although the brain represents only 2% of the body weight, it receives 15% of the cardiac output, 20% of total body oxygen consumption, and 25% of total body glucose utilization.^[51] The demands of the brain limit its size in some species, such as bats.^[52] The brain mostly utilizes glucose for energy, and deprivation of glucose, as can happen in hypoglycemia, can result in loss of consciousness. The energy consumption of the brain does not vary greatly over time, but active regions of the cortex consume somewhat more energy than inactive regions: this fact forms the basis for the functional brain imaging methods PET and fMRI.^[53]

Effects of damage and disease

Even though it is protected by the skull and meninges, surrounded by cerebrospinal fluid, and isolated from the bloodstream by the blood-brain barrier, the delicate nature of the brain makes it vulnerable to numerous diseases and several types of damage. Because these problems generally manifest themselves differently in humans than in other species, an overview of brain pathology and how it can be treated is deferred to the Human brain, Brain damage, and Neurology articles.

Brain and mind

It is not easy to understand the relationship between the physical brain and something as ethereal as the mind. It is hard to doubt that a relationship of some sort exists: the clearest evidence is that numerous drugs, which obviously act directly on the physical substance of the brain, have strong effects on the mind. But what is the upshot? Does this mean that the brain is the mind? Or only that they are bound together in some intimate way? Many people have had a strong intuition, or at least a strong wish to believe, that the mind is fundamentally a separate thing, with an independent existence, capable perhaps of detaching from the body and surviving even after death.

Through most of history the great majority of people, including philosophers, found it inconceivable that anything like thought could be implemented by what is in essence a mere piece of meat. Even Descartes, with his mechanistic philosophy, could not imagine how this could be. He had no problem explaining reflexes and other simple behaviors in mechanistic terms, but he could not believe that complex thought—and language in particular—could be explained in the same way. The invention of computers has made a great difference here. We can now see all around us machines capable of processing language in sophisticated ways—not with the full sophistication of a human mind, but nevertheless in ways that earlier generations could not guess at. Nevertheless, some philosophers continue to argue that there are properties of the human mind that cannot, in principle, be explained mechanistically.

This problem—the mind-body problem—is one of the central issues in the history of philosophy. The brain is the physical and biological matter contained within the skull, responsible for electrochemical neuronal processes while the mind consists of mental attributes, like beliefs, desires, and perceptions. There are scientifically demonstrable correlations between mental events and neuronal events; the philosophical question is whether these phenomena are identical, at least partially distinct, or related in some unknown way. There are three major schools of thought concerning the answer: dualism, materialism, and idealism. Dualism holds that the mind exists independently of the brain;^[54] materialism holds that mental phenomena are identical to neuronal phenomena;^[55] and idealism holds that only mental substances and phenomena exist.^[55]

In addition to the philosophical questions, the relationship between mind and brain involves a number of scientific questions. What is the detailed relationship between thought and brain activity? What are the mechanisms by which drugs influence thought? What is consciousness, in physical terms, and what are the neural correlates of consciousness? These questions fall into the domain of cognitive neuroscience.

How the brain is studied

Fields of study

Neuroscience seeks to understand the nervous system, including the brain, from a biological and computational perspective. Psychology seeks to understand behavior and the brain. Neurology refers to the medical applications of neuroscience. The brain is also one of the most important organs studied in psychiatry, the branch of medicine which exists to study, prevent, and treat mental disorders.^[56]^[57]^[58] Cognitive science seeks to unify neuroscience and psychology with other fields that concern themselves with the brain, such as computer science (artificial intelligence and similar fields) and philosophy.

Methods of observation

Each method for observing activity in the brain has its advantages and drawbacks.

Electrophysiology

Electrophysiology allows scientists to record the electrical activity of individual neurons or groups of neurons.

EEG

By placing electrodes on the scalp one can record the summed electrical activity of the cortex in a technique known as electroencephalography (EEG). EEG measures the mass changes in electrical current from the cerebral cortex, but can only detect changes over large areas of the brain with very little sub-cortical activity.

MEG

Apart from measuring the electric field around the skull it is possible to measure the magnetic field directly in a technique known as magnetoencephalography (MEG). This technique has the same temporal resolution as EEG but much better spatial resolution, although admittedly not as good as fMRI. The main advantage over fMRI is a direct relationship between neural activation and measurement.

fMRI and PET

Functional magnetic resonance imaging (fMRI) measures changes in blood flow in the brain, but the activity of neurons is not directly measured, nor can it be distinguished whether this activity is inhibitory or excitatory. fMRI is a noninvasive, indirect method for measuring neural activity that is based on BOLD; Blood Oxygen Level Dependent changes. The changes in blood flow that occur in capillary beds in specific regions of the brain are thought to represent various neuronal activities (metabolism of synaptic reuptake). Similarly, a positron emission tomography (PET), is able to monitor glucose and oxygen metabolism as well as neurotransmitter activity in different areas within the brain which can be correlated to the level of activity in that region.

Behavioral

Behavioral tests can measure symptoms of disease and mental performance, but can only provide indirect measurements of brain function and may not be practical in all animals. In humans however, a neurological exam can be done to determine the location of any trauma, lesion, or tumor within the brain, brain stem, or spinal cord.

Anatomical

Autopsy analysis of the brain allows for the study of anatomy and protein expression patterns, but is only possible after the human or animal is dead. Magnetic resonance imaging (MRI) can be used to study the anatomy of a living creature and is widely used in both research and medicine.

Other studies

Computer scientists have produced simulated "artificial neural networks" loosely based on the structure of neuron connections in the brain. Some artificial intelligence research seeks to replicate brain function—although not necessarily brain mechanisms—but as yet has been met with only limited success.

Creating algorithms to mimic a biological brain is very difficult because the brain is not a static arrangement of circuits, but a network of vastly interconnected neurons that are constantly changing their connectivity and sensitivity. More recent work in both neuroscience and artificial intelligence models the brain using the mathematical tools of chaos theory and dynamical systems. Current research has also focused on recreating the neural structure of the brain with the aim of producing human-like cognition and artificial intelligence.

History of understanding of the brain

Early views were divided as to whether the seat of the soul lies in the brain or heart. On one hand, it was impossible to miss the fact that awareness feels like it is localized in the head, and that blows to the head can cause unconsciousness much more easily than blows to the chest, and that shaking the head causes dizziness. On the other hand, the brain to a superficial examination seems inert, whereas the heart is constantly beating. Cessation of the heartbeat means death; strong emotions produce changes in the heartbeat; and emotional distress often produces a sensation of pain in the region of the heart ("heartache"). Aristotle favored the heart, and thought that the function of the brain is merely to cool the blood. Democritus, the inventor of the atomic theory of matter, favored a three-part soul, with intellect in the head, emotion in the heart, and lust in the vicinity of the liver.^[59] Hippocrates, the "father of medicine", was entirely in favor of the brain. In On the Sacred Disease, his account of epilepsy, he wrote:

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 the same organ we become mad and delirious, and fears and terrors assail us, some by night, and some by day, and dreams and untimely wanderings, and cares that are not suitable, and ignorance of present circumstances, desuetude, and unskilfulness. All these things we endure from the brain, when it is not healthy…
— Hippocrates, ^[60]

The famous Roman physician Galen also advocated the importance of the brain, and theorized in some depth about how it might work. Even after physicians and philosophers had accepted the primacy of the brain, though, the idea of the heart as seat of intelligence continued to survive in popular idioms, such as "learning something by heart".^[61] Galen did a masterful job of tracing out the anatomical relationships between brain, nerves, and muscles, demonstrating that all muscles in the body are connected to the brain via a branching network of nerves. He postulated that nerves activate muscles mechanically, by carrying a mysterious substance he called pneumata psychikon, usually translated as "animal spirits". His ideas were widely known during the Middle Ages, but not much further progress came until the Renaissance, when detailed anatomical study resumed, combined with the theoretical speculations of Descartes and his followers. Descartes, like Galen, thought of the nervous system in hydraulic terms. He believed that the highest cognitive functions—language in particular—are carried out by a non-physical res cogitans, but that the majority of behaviors of humans and animals could be explained mechanically. The first real progress toward a modern understanding of nervous function, though, came from the investigations of Luigi Galvani, who discovered that a shock of static electricity applied to an exposed nerve of a dead frog could cause its leg to contract.

Notes

^ Man on his nature
^ Gehring, 2005
^ Nickel, 2002
^ Grillner & Wallén, 2002
^ 23 Problems in Systems Neuroscience
^ Principles of neural science, Ch. 17
^ ^a ^b Carpenter's Human Neuroanatomy, Ch. 1
^ Principles of neural science, p 324
^ Aboitiz et al, 2003
^ Neurobiology, p 3
^ Balavoine & Adoutte, 2003
^ Evolution of Organ Systems, p 110
^ ^a ^b Butler, 2000
^ In Search of Memory
^ Flybrain web site
^ Konopka & Benzer, 1971
^ Shin et al, 1985
^ WormBook web site
^ Hobert, WormBook
^ White et al, 1986
^ Principles of brain evolution
^ Principles of Neural Science, p 1019
^ Principles of Neural Science, Ch. 17
^ Northcutt, 2008
^ Reiner et al, 2005
^ Swaab et al, The human hypothalamus
^ Jones, The thalamus
^ Principles of Neural Science, Ch. 42
^ Saitoh et al, 2007
^ Puelles, 2001
^ Salas et al, 2003
^ Grillner et al, 2005
^ Armstrong, 1983
^ Savage et al, 2004
^ Jerison, 1973
^ Finlay et al, 2001
^ Kappelman, 1993
^ Holloway, 1995
^ Roth & Dicke, 2005
^ Principles of Neural Development, Ch. 1
^ Principles of Neural Development, Ch. 4
^ Principles of Neural Development, Chs. 5, 7
^ Principles of Neural Development, Ch. 12
^ Wong, 1999
^ Principles of Neural Development, Ch. 6
^ Ridley, Nature vs Nurture
^ Wiesel, 1982
^ van Praag et al, 2000
^ See Dale's principle
^ See muscle
^ Clark & Sokoloff, 1999
^ Safi et al, 2005
^ Raichle & Gusnard, 2002
^ Hart, 1996
^ ^a ^b Lacey, 1996
^ Storrow, H.A. (1969). Outline of Clinical Psychiatry. New York: Appleton-Century-Crofts, p. 1. ISBN 978-0-39-085075-1
^ Lyness, J.M. (1997). Psychiatric Pearls. Philadelphia: F.A. Davis Company, p. 3. ISBN 978-0-80-360280-9
^ Guze, S.B. (1992). Why Psychiatry Is a Branch of Medicine. New York: Oxford University Press, p. 4. ISBN 978-0-19-507420-8
^ History of Neuroscience, p 14
^ On the Sacred Disease
^ Encylopedia of Word and Phrase Origins

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External links

How Your Brain Works at HowStuffWorks
The HOPES Brain Tutorial at hopes.stanford.edu
Comparative Mammalian Brain Collection
Brain Research News from ScienceDaily
BrainInfo for Neuroanatomy
Neuroscience for kids
Everything you wanted to know about the brain – Provided by New Scientist.
Fact sheets on brain injury - causes, effects and coping strategies
Neuroscience wiki.
BrainMaps.org, interactive high-resolution digital brain atlas based on scanned images of serial sections of both primate and non-primate brains
Scientific American Magazine (September 2003 Issue) Ultimate Self-Improvement
Brain Research and Information Network B.R.A.I.N.
The Brain from Top to Bottom

Template:Link FA

[1] Man on his nature

[2] Gehring, 2005

[3] Nickel, 2002

[4] Grillner & Wallén, 2002

[5] 23 Problems in Systems Neuroscience

[6] Principles of neural science, Ch. 17

[CarpenterCh1-7] Carpenter's Human Neuroanatomy, Ch. 1

[8] Principles of neural science, p 324

[9] Aboitiz et al, 2003

[10] Neurobiology, p 3

[11] Balavoine & Adoutte, 2003

[12] Evolution of Organ Systems, p 110

[butler-13] Butler, 2000

[14] In Search of Memory

[15] Flybrain web site

[16] Konopka & Benzer, 1971

[17] Shin et al, 1985

[18] WormBook web site

[19] Hobert, WormBook

[20] White et al, 1986

[21] Principles of brain evolution

[22] Principles of Neural Science, p 1019

[23] Principles of Neural Science, Ch. 17

[24] Northcutt, 2008

[25] Reiner et al, 2005

[26] Swaab et al, The human hypothalamus

[27] Jones, The thalamus

[28] Principles of Neural Science, Ch. 42

[29] Saitoh et al, 2007

[30] Puelles, 2001

[31] Salas et al, 2003

[32] Grillner et al, 2005

[33] Armstrong, 1983

[34] Savage et al, 2004

[35] Jerison, 1973

[36] Finlay et al, 2001

[37] Kappelman, 1993

[38] Holloway, 1995

[39] Roth & Dicke, 2005

[40] Principles of Neural Development, Ch. 1

[41] Principles of Neural Development, Ch. 4

[42] Principles of Neural Development, Chs. 5, 7

[43] Principles of Neural Development, Ch. 12

[44] Wong, 1999

[45] Principles of Neural Development, Ch. 6

[46] Ridley, Nature vs Nurture

[47] Wiesel, 1982

[48] van Praag et al, 2000

[49] See Dale's principle

[50] See muscle

[51] Clark & Sokoloff, 1999

[52] Safi et al, 2005

[53] Raichle & Gusnard, 2002

[54] Hart, 1996

[DicPhil-55] Lacey, 1996

[Storrow1-56] Storrow, H.A. (1969). Outline of Clinical Psychiatry. New York: Appleton-Century-Crofts, p. 1. ISBN 978-0-39-085075-1

[Lyness3-57] Lyness, J.M. (1997). Psychiatric Pearls. Philadelphia: F.A. Davis Company, p. 3. ISBN 978-0-80-360280-9

[Guze4-58] Guze, S.B. (1992). Why Psychiatry Is a Branch of Medicine. New York: Oxford University Press, p. 4. ISBN 978-0-19-507420-8

[59] History of Neuroscience, p 14

[60] On the Sacred Disease

[61] Encylopedia of Word and Phrase Origins

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

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