What is the brain?

Structure and Functions

The human brain is a complex structure that is composed of two major classes of individual cells: nerve cells (or neurons) and neuroglial cells (or glial cells). It has been estimated that the adult human brain has around one hundred billion neurons and an even larger number of glial cells. An average adult brain weighs about 1,400 grams and has a volume of 1,200 milliliters. These values tend to vary directly with the person’s body size; therefore, males have a brain that is typically 10 percent larger than that of females. There is no correlation of intelligence with brain size, however, as witnessed by the fact that brains as small as 750 milliliters or larger than 2,000 milliliters still show normal functioning.

Neurons process and transmit information. The usual structural features of a neuron include a cell body (or soma), anywhere from several to several hundred branching dendrites that are extensions from the soma, and a typically longer extension known as the axon with one or several synaptic terminals at its end.

The information that is processed and transmitted in the brain takes the form of very brief electrochemical events, with a typical duration of less than two milliseconds, called action potentials or nerve impulses. These impulses most often originate near the point at which the axon and soma are joined and then travel at speeds of up to 130 meters per second along the axon to the synaptic terminals.

It is at the synaptic terminals that one neuron communicates its information to other neurons in the brain. These specialized structural points of neuron-to-neuron communication are called synapses. Most synapses are found on the dendrites and soma of the neuron that is to receive the nerve signal. A neuron may have as many as fifty thousand synapses on its surface, although the average seems to be around three thousand. It is thought that as many as three hundred trillion synapses may exist in the adult brain.

The neuroglia function as supporting cells. They have a variety of important duties that include acting as a supporting framework for neurons, increasing the speed of impulse conduction along axons, acting as removers of waste or cellular debris, and regulating the composition of the fluid environment around the neurons in order to maintain optimal working conditions in the brain. Neuroglia actually make up about half of the brain’s total volume.

The brain can be divided into two major components: gray matter and white matter, both named for their general appearance. The gray matter is composed primarily of neural soma, dendrites, and axons that transmit information at relatively slow speeds. The white matter is made of collections of axons that have layers of specialized glial cells wrapped around them. This enables much faster information transfer along these axons.

The brain has six major regions. Beginning from the top of the spinal cord and moving progressively upward, these regions are the medulla oblongata, the pons, the cerebellum, the mesencephalon (or midbrain), the diencephalon, and the cerebrum.

The initial lower portion of the medulla oblongata
resembles the spinal cord. The medulla has a variety of functions besides the simple relaying of various categories of sensory information to higher-brain centers. Within the medulla there are a number of centers that are important for the execution and regulation of basic survival and maintenance duties. These duties are called visceral functions and include jobs such as regulating the heart rate, breathing, digestive actions, and blood pressure.

The term pons comes from the Latin word meaning "bridge." The pons serves as a bridge from the medulla oblangata to the cerebellum, which is actually situated on the backside of the brain stem. The pons contains tracts and nuclei that permit communication between the cerebellum and other nervous system structures. Some pontine nuclei facilitate the control of such voluntary and involuntary muscle actions as chewing, breathing, and moving the eyes; other nuclei process information related to the sense of balance.

The cerebellum is a small brain in itself. The two main functions of the cerebellum are to make adjustments, quickly and automatically, to the muscles of the body that assist in maintaining balance and posture and to coordinate the activities of the skeletal muscles involved in movements or sequences of movements, thereby promoting smooth and precise actions. These functions are possible because of the input of sensory information to the cerebellum from position sensors in the muscles and joints; from visual, touch, and balance organs; and even from the sense of hearing. There are also many communication channels to and from the cerebellum and other brain areas concerned with the generation and control of movements. While the cerebellum is not the origin of commands that initiate movements, it does store the memories of how to perform patterns of muscle contractions that are used to execute learned skills, such as serving a tennis ball.

The mesencephalon, or midbrain, is located just above the pons. The midbrain contains pathways carrying sensory information upward to higher-brain centers and transmitting motor signals from higher regions down to lower-brain and spinal cord areas involved in movements.

Two important pairs of nuclei, the inferior and superior colliculi, are found on the backside of the mesencephalon. They coordinate visual and acoustic reflexes involving eye and head movements, such as eye focusing and orienting the head and body toward a sound source. The nucleus known as the substantia nigra operates with nuclei in the cerebrum to generate the patterns and rhythms of such activities as walking and running. Additional mesencephalic nuclei are important for the involuntary control of muscle tone, posture maintenance, and the control of eye movements.

The diencephalon, located above the midbrain, contains the two important brain structures known as the thalamus and hypothalamus. The thalamus is the final relay for all sensory signals (except the sense of smell) before they arrive at the cerebral cortex (the cerebrum’s outer covering of gray matter). The hypothalamus is important for regulating drives and emotions, and it serves as a master link between the nervous and endocrine systems.

The thalamus is a collection of different nuclei. Some cooperate with nuclei in the cerebrum to process memories and generate emotional states. Other nuclei have complex involvement in the interactions of the cerebellum, cerebral nuclei, and motor areas of the cerebral cortex.

The relatively small hypothalamus plays many crucial roles that help to maintain stability in the body’s internal environment. It regulates food and liquid intake, blood pressure, heart rate, breathing, body temperature, and digestion. Other significant duties encompass the management of sexual activity, rage, fear, and pleasure.

The final major brain region is the cerebrum, which is the largest of the six regions and the seat of higher intellectual capabilities. Sensory information that reaches the cerebrum also enters into a person’s conscious awareness. Voluntary actions originate in the cerebral neural activities.

The cerebrum is divided into two cerebral hemispheres, each covered by the gray matter known as the cerebral cortex. Below the cortex is the white matter, which consists of massive bundles of axons carrying signals between various cortical areas, down from the cortex to lower areas, and up into the cortex from lower areas. Embedded in the white matter are also a number of cerebral nuclei.

The cerebral cortex has areas that are the primary sensory areas for each of the senses and other areas whose major duties deal with the origin and planning of motor activities. The association areas of the cortex integrate and process sensory signals, often resulting in the initiation of appropriate motor responses. Cortical integrative centers receive information from different association areas. The integrative centers perform complex analyses of information (such as predicting the consequences of various possible responses) and direct elaborate motor activities (such as writing).

The cerebral nuclei, also called the basal nuclei or basal ganglia, form components of brain systems that have complex duties such as the regulation of emotions, the control of muscle tone and the coordination of learned patterns of movement, and the processing of memories.

The electrochemical signal that constitutes an action potential
in a neuron, and that is sent along the neuron’s axon to the synaptic contacts formed with other neurons in the brain, is the basic unit of activity in neural tissue. Although the electrical voltage generated by a single action potential is very small and difficult to measure, the tremendous number of neurons active at any moment results in voltages large enough to be measured at the scalp with appropriate instruments called electroencephalographs. The recorded signals are known as an electroencephalogram (EEG).

Although interpreting an EEG can be compared to standing outside a football stadium filled with screaming fans and trying to discern what is happening on the playing field by listening to the crowd noises, it still provides clinically useful information and is used regularly in clinics around the world each day. The typical EEG signal appears as a series of wavy patterns whose size, length, shape, and location of best recording on the head provide valuable indications concerning the conditions of brain regions beneath the recording electrodes placed on the scalp.

Disorders and Diseases

One of the most useful applications of the EEG is in the diagnosis of epilepsy. Epilepsy
is a group of disorders originating in the brain. There are multiple possible causes. Epilepsy is characterized by malfunctions of the motor, sensory, or even psychic operations of the brain, and there are often accompanying convulsive movements during the attack.

The most common type is known as idiopathic epilepsy, so called because there is no known cause of the attacks. The usual episode occurs suddenly as a large group of neurons begins to produce action potentials in a very synchronized fashion (called a seizure), which is not the typical mode of action in neural tissue. There may be no impairment of consciousness or a complete loss of consciousness, and the seizure may be restricted to a localized area of brain tissue or may spread over the entire brain. When areas of the brain that generate or control movements become involved, the patient will exhibit varying degrees of involuntary muscle contractions or convulsions.

Some cases of epilepsy can be traced to definite causes such as brain tumors, brain injuries, drug abuse, adverse drug reactions, or infections that have entered the brain. Regardless of the cause, the diagnosis is often made through examination of the EEG, whereby a trained examiner can quickly identify the EEG abnormalities characteristic of epilepsy.

The usual treatment is directed toward preventing the synchronized bursts of neural activity. This is most often achieved by administering anticonvulsive drugs such as phenobarbital or phenytoin. These agents block the transmission of neural signals in the epileptic regions and thereby suppress the explosive episodes of synchronized neuronal discharges that induce the seizures. Many epileptics are successfully treated by this approach and are able to lead normal, productive lives, free from the uncontrollable seizures. In some cases, the medication can eventually be discontinued and the patient will never again suffer a seizure.

Unfortunately, there are also cases where even the strongest medications do not prevent the seizures, or only do so with debilitating side effects. In the most severe cases, the patients may have dozens of seizures each day, making any form of normal existence impossible. In addition, the large number of seizures eventually can lead to permanent brain damage. For some of these patients, the most drastic form of treatment has been used: surgical removal of the brain tissue responsible for the seizures. This technique is accompanied by great risk because of the danger that removing a portion of brain tissue may leave the patient unable to speak or to speak intelligently, unable to understand spoken words, unable to interpret visual information, or suffering from any of a wide variety of behavioral disturbances, depending on the precise area of the brain that has been removed.

Although this approach is not appropriate in all cases, it has been successful in many. For these patients, success is usually defined as the possibility, following surgery, to control or prevent future seizures through the use of anticonvulsive drugs and to resume a normal life or a life that is much more normal than it was before surgery.

A varied group of disorders known as dyskinesias causes difficulty in the performance of voluntary movements. The movements actually look like normal body movements or portions of normal movements. Dyskinesia often results from problems involving the basal nuclei. When the basal nuclei are affected, the dyskinesic movements usually do not occur during sleep and are reduced during periods of emotional tranquillity. Anxiety, emotional tension, and stressful conditions, however, cause the dyskinesia to become worse. These observations can be explained by the fact that neural pathways are known to connect the brain centers involved with the generation of emotional states to the basal nuclei.

One example of a dyskinesia affecting the basal nuclei is the inherited condition of Huntington’s disease (or Huntington’s chorea), for which no cure exists. A chorea is a dyskinesia in which the patient’s movements are quick and irregular. Huntington’s chorea first makes its appearance when the patient is in middle age. It results in the progressive degeneration of the basal nuclei, known as the corpus striatum, that are located in the cerebrum. Some of the common symptoms are involuntary facial grimacing, jaw and tongue movements, twisting and turning movements of the torso, and speaking difficulties. As the brain atrophy (degeneration) progresses, the patients become totally disabled. Death usually results ten to fifteen years following the appearance of the first symptoms.

A category of generalized disturbances of higher-brain function is known as dementia. Dementia is characterized by a generalized deficiency of intellectual performance, mental deterioration, memory impairment, and limited attention span. These are often accompanied by changes in personality such as increased irritability and moodiness.

Various diseases can cause dementia. One of the most frequently observed is known as Alzheimer’s disease; it is progressive and usually develops between the ages of forty and sixty. The disease is marked by the death of neurons in the cerebral cortex and the deep cerebral regions known as the nucleus basalis and the hippocampus. The exact cause of neural death in Alzheimer’s disease is unknown. While some cases are inherited, other instances seem to appear without any family history of the disease. Death usually occurs within ten years after the appearance of the first symptoms, and no cure exists.

The areas of the brain showing neural degeneration also have abnormal collections of a specific type of protein. The appearance of this protein in the blood and the fluids that surround the brain is a clinical sign of Alzheimer’s disease. The areas of the brain that deteriorate during the progression of this disease illustrate the functional roles played by these regions. The hippocampus, in particular, is crucial for learning, the storage of long-term memories, memory of recent events, and the sense of time. Therefore, the death of hippocampal neurons helps to explain the memory disturbances and related behavioral changes seen in Alzheimer’s disease patients.

Perspective and Prospects

Given the complexity of the human brain, understanding its structure and function is the ultimate challenge to medical science. The challenge exists because in order to treat brain disorders rationally, it is necessary to know how a normal brain functions. An appreciation of this can be gleaned by studying the history of some approaches used through the ages to treat brain disorders.

For example, in the Middle Ages it was a common practice to treat people with epilepsy by cutting open the patient’s scalp and pouring salt into the wound (all of which was performed without anesthesia, since anesthetics were not yet known). The purpose of this treatment was to poison the spirits possessing the patient, forcing them to leave.

As modern science discovered the cellular basis of life, such measures were gradually replaced with treatments directed toward the biochemical imbalances, infections, or interruptions of blood flow that were found to be the cause of many brain disorders. The development of nonsurgical techniques permitting the visualization of the brain regions that are active, or inactive, during various tasks or illnesses greatly advanced the understanding of brain function and improved diagnosis, the planning of effective treatments, and the tracking of either the improvement or the deterioration of patients.

Late in the 1970s, the disease known as acquired immunodeficiency syndrome (AIDS) attracted the attention of the world’s scientists. AIDS is caused by the human immunodeficiency virus (HIV). A significant portion of AIDS patients experience various neurological problems, including difficulties of movement, loss of memory, and cognitive disturbances. In some cerebral cortical areas, as many as half of the neurons may die. To understand how the virus causes these effects, it is necessary to analyze how the brain’s components function when infected by the virus and then form a clear explanation of the consequences of viral infection.

HIV actually infects certain classes of neuroglial cells. Infection of these glial cells causes them to release distinct types of chemicals that can be toxic to neurons. One type of glial cell, known as the astrocyte, can begin to appear in abnormally large numbers as a result of these chemicals being released. In turn, the presence of large numbers of astrocytes provokes the release of even more of the toxic chemicals. This sort of effect is referred to as a positive feedback loop. The significance of this cascade of mutually stimulating events (neurotoxic chemicals causing astrocytes to appear in greater numbers, and increased numbers of astrocytes causing more production of neurotoxic chemicals) is that only a few HIV-infected cells can trigger extensive neural damage.

Additionally, a protein part of the virus, called gp120, can stimulate release of the same neurotoxic chemicals and can disrupt the normal functioning of the astrocytes. One important function of astrocytes is to regulate the chemical environment of neurons by removing certain types of chemicals. One of these chemicals, called glutamate, is normally present and used by some neurons to send signals to other neurons at their synaptic contacts. When glutamate is not promptly removed from the environment of the target neurons, however, it becomes toxic to the neurons and kills them. The HIV protein gp120 disrupts the ability of astrocytes to remove glutamate, thereby increasing the death of neurons in the brain as they become exposed to toxic levels of glutamate.

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