Interest in the brain and human behavior is as old as the human race. Records dating back to 3000 BC in Egypt describe brain anatomy and various brain injuries. Currently the field of neuroscience is rapidly expanding and includes many disciplines that combine for a more complete understanding of the human brain and how it is integrated with the body and the human environment (Figure 5-1). All nurses should have a working knowledge of the normal structure and function of the brain, just as all nurses should know about the structure and function of the heart.

Structure and Function of the Brain

The brain weighs about 3 pounds. It is composed of trillions of groups of cells that have formed highly specific structures and sophisticated communication pathways that have changed over millions of years of evolution (Box 5-1). A brief review of key brain regions is presented in Figures 5-2 through 5-6 and in Box 5-2.

BOX 5-1   ABOUT THE BRAIN

• At birth, an infant’s brain is almost the same size as an adult’s brain and contains most of the brain cells for one’s entire life.

• From birth, the brain matures from back to front. With aging, it degenerates in the opposite direction.

• A newborn’s brain grows about three times its size in the first year.

• The brains of 2-year-old children consume twice as much glucose as do adult brains.

• Compared to an environment with little stimulation, a stimulating environment can give a child a 25% greater ability to learn.

• By the age of 7 years, our brains are 95% of their adult size.

• It is a myth that we use only 10% of our brains. In fact, we use it all.

• Your skin weighs twice as much as your brain.

• The brain can live for 4 to 6 minutes without oxygen, and then it begins to die. No oxygen for 5 to 10 minutes will result in permanent brain damage.

BOX 5-2   STRUCTURE AND FUNCTION OF THE BRAIN

Cerebrum

Largest portion of the brain

Responsible for conscious perception, thought, and motor activity

Governs muscle coordination and the learning of rote movements

Can override most other systems

Divided into two hemispheres, each of which is divided into four lobes

Dominant Hemisphere

Left side is dominant in most people (in 95% of right-handed and more than 50% of left-handed people)

Responsible for the production and comprehension of language, mathematical ability, and the ability to solve problems in a sequential, logical fashion

Nondominant Hemisphere

Right side is nondominant in most people

Responsible for musical skills, recognition of faces, and tasks requiring comprehension of spatial relationships

Corpus Callosum

Largest fiber bundle in the brain

Connects the two cerebral hemispheres and passes information from one to the other, welding the two hemispheres together into a unitary consciousness, allowing the “right hand to know what the left hand is doing”

Cerebral Cortex

A few millimeters thick and about 2.5 square feet in area

Sheet of gray matter containing 30 billion neurons interconnected by almost 70 miles of axons and dendrites

Forms the corrugated surface of the four lobes of the cerebral hemispheres

Connected to various structures of the brain and has a great deal to do with the abilities we think of as uniquely human, such as language and abstract thinking, as well as basic aspects of perception, movement, and adaptive response to the outside world

Functional areas have been mapped by imaging technology

Damage to certain cortical areas usually results in predictable deficits, depending on the area affected

Frontal Lobes

Aid in planning for the future, motivation, control of voluntary motor function, and production of speech

Play an important part in emotional experience and expression of mood

Clinical example: Aphasia (absent or defective speech or comprehension) results from a lesion in the language areas of the cortex. The several types of aphasia depend on the site of the lesion. Damage to Broca area, which contains the motor programs for the generation of language, results in expressive, or motor, aphasia, with difficulty producing either written or spoken words but no difficulty comprehending language.

Parietal Lobes

Reception and evaluation of most sensory information (excluding smell, hearing, and vision)

Concerned with the initial processing of tactile and proprioceptive (sense of position) information, complex aspects of spatial orientation and perception, and the comprehension of language (share Wernicke area with the temporal lobes)

Damage within the parietal lobe may result in difficulty recognizing familiar objects, surroundings, or people (visual agnosia)

Central Sulcus

Groove or fissure on the surface of the brain that divides the frontal and parietal lobes

Temporal Lobes

Receive and process auditory information, involved in higher-order processing of visual information, involved in complex aspects of memory and learning, and are important in the comprehension of language

Associated with functions such as abstract thought and judgment

Clinical example: Damage to Wernicke area, which contains the mechanisms for the formulation of language, results in receptive, or sensory, aphasia, in which words are produced but their sequence is defective in linguistic content, resulting in paraphasia (word substitutions), neologisms (insertion of new and meaningless words), or jargon (fluent but unintelligible speech), and a general deficiency in the comprehension of language is noted. If the lesion occurs in the connection between Broca area and Wernicke area, conduction aphasia results, in which a person has poor repetition but good comprehension.

Lateral Fissure

Separates the temporal lobe from the rest of the cerebrum

Occipital Lobes

Reception and integration of visual input

Damage to the occipital lobes can result in blindness

Diencephalon

Constitutes only 2% of the central nervous system (CNS) by weight

Has extremely widespread and important connections; the great majority of sensory, motor, and limbic pathways involve the diencephalon

Thalamus

Composes 80% of the diencephalon

All sensory pathways and many other anatomical loops relay in the thalamus

Takes sensory information and relays it to areas throughout the cortex

Influences prefrontal cortical functions, such as affect and foresight

Influences mood and general body movements associated with strong emotions, such as fear or rage

Pineal Gland

Endocrine gland involved in reproductive cycles

During darkness it secretes an antigonadotropic hormone called melatonin, which decreases during light, thus increasing gonadal function

Important in mammals with seasonal sexual cycles; its effects in humans are not yet clear, although tumors of the pineal gland affect human sexual development

Also may be involved in the sleep-wake cycle

Hypothalamus

Weighs only 4 grams

Major control center for the pituitary gland; for maintaining homeostasis; and for regulating autonomic, endocrine, emotional, and somatic functions

Controls various visceral functions and activities involved in basic drives and is very important in a number of functions that have emotional and mood relationships

Directly involved in stress-related and psychosomatic illnesses and with feelings of fear and rage

Regulates feeding and drinking behavior, temperature regulation, cardiac function, gut motility, and sexual activity

Coordinates responses for the sleep-wake cycle to other areas of the body

Contains the mamillary bodies, which are involved in olfactory reflexes and emotional responses to odors

Brainstem

Connects the spinal cord to the brain

Location of cranial nerve nuclei

Controls automatic body functions, such as breathing and cardiovascular activity

Midbrain

Contains ascending and descending nerve tracts

Visual cortex center

Part of auditory pathway

Regulates the reflexive movement of the eyes and head

Aids in the unconscious regulation and coordination of motor activities

Contains the part of the basal ganglia, the substantia nigra, that manufactures dopamine

Pons

Contains ascending and descending nerve tracts

Relays between cerebrum and cerebellum

Reflex center

Contains the locus ceruleus, which manufactures most of the brain’s norepinephrine

Medulla Oblongata

Conduction pathway for ascending and descending nerve tracts

Conscious control of skeletal muscles

Involved in functions such as balance, coordination, and modulation of sound impulses from the inner ear

Center for several important reflexes: heart rate, breathing, swallowing, vomiting, coughing, sneezing

Reticular Formation

Central core of the brainstem

Controls cyclical activities, such as the sleep-wake cycle (called the reticular activating system [RAS])

Plays an important role in arousing and maintaining consciousness, alertness, and attention

Contributes to the motor system, respiration, cardiac rhythms, and other vital body functions

Clinical example: Damage to the RAS can result in coma. General anesthetics function by suppressing this system. It also may be the target of many tranquilizers. Ammonia (smelling salts) stimulates the RAS, resulting in arousal.

Basal Ganglia

Several deep gray matter structures that are related functionally and are located bilaterally in the cerebrum, diencephalon, and midbrain

Control muscle tone, activity, and posture

Coordinate large-muscle movements

Major effect is to inhibit unwanted muscular activity

Cause extrapyramidal syndromes when dysfunctional

Clinical example: Parkinson disease (characterized by muscular rigidity; a slow, shuffling gait; and a general lack of movement) is associated with a dysfunction of the basal ganglia, probably a destruction of the dopamine-producing neurons of the substantia nigra (part of the basal ganglia but located in the midbrain).

Limbic System

Forms the limbus, or border, of the temporal lobes and is intimately connected to many other structures of the brain

Concerned both with subjective emotional experiences and with changes in body functions associated with emotional states

Particularly involved in aggressive, submissive, and sexual behavior and with pleasure, memory, and learning

Associated with mood, motivation, and sensations, all central to preservation

Clinical example: Klüver-Bucy syndrome develops when the entire limbic system is removed or destroyed. Symptoms include fearlessness and placidity (absence of emotional reactions), an inordinate degree of attention to sensory stimuli (ceaseless and intrusive curiosity), and visual agnosia (the inability to recognize anything).

Hippocampus

Consolidates recently acquired information about facts and events, somehow turning short-term memory into long-term memory

Contains large amounts of neurotransmitters

Hippocampal volume loss (atrophy) associated with major depressive episodes; the direct effects of this atrophy are not yet fully understood

Clinical example: Surgical removal of the hippocampus results in the inability to form new memories of facts and events (names of new acquaintances, day-to-day events, inability to remember why a task was begun), although long-term memory, intelligence, and the ability to learn new skills are unaffected. A similar memory problem is Korsakoff syndrome, in which patients have intact intelligence but cannot form new memories. They typically confabulate (make up answers to questions), which occurs when the hippocampus and surrounding areas are damaged by chronic alcoholism. This also is seen in Alzheimer disease, in which the memory loss is profound, and extensive cellular degeneration in the hippocampus is noted.

Amygdala

Generates emotions from perceptions and thoughts (presumably through its interactions with the hypothalamus and prefrontal cortex)

Contains many opiate receptors

Amygdala hypertrophy (enlargement) is associated with various depressive syndromes

Clinical example: Electrical stimulation of the amygdala in animals causes responses of defense, raging aggression, or fleeing. In humans the most common response is fear and its related autonomic responses (dilation of the pupils, increased heart rate, and release of adrenaline). Conversely, bilateral destruction of the amygdala causes a great decrease in aggression, and animals become tame and placid. This is thought to be another kind of memory dysfunction that impairs the ability to learn or remember the appropriate emotional and autonomic responses to stimuli.

Fornix

Two-way fiber system that connects the hippocampus to the hypothalamus

Cerebellum

“Little brain”

Full range of sensory inputs finds its way here and in turn projects to various sites in the brainstem and thalamus

Although it is extensively involved with the processing of sensory information, it also is part of the motor system and is involved in equilibrium, muscle tone, postural control, and coordination of voluntary movements

It is thought that, because of connections to other brain regions, the cerebellum may be involved in cognitive, behavioral, and affective functions

Clinical example: The malnutrition often accompanying chronic alcoholism causes a degeneration of the cerebellar cortex, resulting in the anterior lobe syndrome in which the legs are primarily affected, and the most prominent symptom is a broad-based, staggering gait and a general incoordination, or ataxia, of leg movements.

Ventricles

Each cerebral hemisphere contains a large cavity, the lateral ventricle

A smaller midline cavity, the third ventricle, is located in the center of the diencephalon, between the two halves of the thalamus

The fourth ventricle is in the region of the pons and medulla oblongata and connects with the central canal of the spinal cord, which extends nearly the full length of the spinal cord

Clinical example: Although the clinical significance of these findings is uncertain, imaging techniques have shown enlargement of the ventricles in many psychiatric disorders, suggesting an atrophy of the many critical structures in the brain with these illnesses.

Spinal Fluid

Cerebrospinal fluid (CSF) is procured from the blood choroid plexuses, located in the ventricles, and fills the ventricles, subarachnoid space (between the brain and the skull), and the spinal cord

CSF bathes the brain with nutrients, cushions the brain within the skull, and exits through the bloodstream

Approximately 140 mL of spinal fluid within the CNS travels from its point of origin to the bloodstream at approximately 0.4 mL/min

Clinical example: Neurotransmitters and their metabolites can be measured in the CSF, plasma, and urine and give an approximation of neurotransmitter production and metabolism in the brain. This provides clues to abnormal neurotransmission in some mental illnesses.

Blood-Brain and Blood-CSF Barriers

Neuronal function requires a microenvironment that is protected from changes elsewhere in the body that may have an adverse effect

Blood-brain and blood-CSF barriers protect the CNS in several ways: Large molecules, such as plasma proteins, present in the blood, are excluded from the CSF and nervous tissue. The brain and spinal cord are protected from neurotransmitters in the blood, such as epinephrine produced by the adrenal gland. Neurotransmitters produced in the CNS are prevented from precipitously leaking into the general circulation. Toxins are excluded either because of their molecular size (too big) or because of their solubility (only substances soluble in water and cell-membrane lipids can pass these barriers); therefore many drugs are not able to enter the brain and spinal cord

The brain develops and changes in utero and throughout the life span. This is known as neural plasticity. During adolescence the efficiency of the brain is refined by eliminating unneeded circuits, called synaptic pruning, and strengthening others. This process allows humans to have a brain that accommodates both its genetic potential and the environmental influences surrounding it.

The changing brain reacts to a variety of influences that can support health or promote illness, both before birth and across the life span. About 100 billion brain cells, or neurons, form groups or structures that are highly specialized. Neurotransmission is the process by which neurons communicate with each other through electrical impulses and chemical messengers.

This communication among neurons is carried out by chemical “first” messengers called neurotransmitters, and gives rise to human activity, body functions, consciousness, intelligence, creativity, memory, dreams, and emotion. Neurotransmission is a key factor in understanding how various regions of the brain function and how interventions, such as medications and other therapies, affect brain activity and human behavior.

Neurotransmitters are manufactured in the neuron and released from the axon, or presynaptic cell, into the synapse, which is the space between neurons. From there the neurotransmitters are received by the dendrite, or postsynaptic cell, of the next neuron. This neurotransmission process makes communication among brain cells possible (Figure 5-7).

Like a key inserted into a lock, each of these chemicals fits precisely into specific receptor cells (made of protein) embedded in the membranes of the axons and dendrites. These receptor cells then either open or close doors (ion channels) into the cell, allowing for the interchange of chemicals, such as ions like sodium (Na⁺), potassium (K⁺), and calcium (Ca²⁺).

This process, known as depolarization, changes the electrical charge of the cell. This change then triggers a cascade of chemical and electrical processes that are caused by a variety of chemicals called second messengers within the cell itself. The second messengers regulate the function of the ion channels, the production of neurotransmitters, and the release of neurotransmitters into the synapse—they continue the process of neurotransmission.

Depending on the chemical composition of the neurotransmitter, the signal it gives either excites the receiving cells, causing them to produce an action, or inhibits the receiving cells, which slows or stops an action. After release into the synapse and communication with receptor cells, the neurotransmitters are transported back from the synapse into the axon in a process called reuptake, where they are stored for future use or are inactivated (metabolized) by enzymes.

The nervous system cells are surrounded by myelin sheaths formed by specialized groups of cells called glial cells. These are support cells that insulate neurons, remove excess transmitters and ions from the extracellular spaces in the brain, provide glucose to some nerve cells, and direct the flow of blood and oxygen to various parts of the brain. Several chambers or ventricles within the brain carry cerebrospinal fluid (CSF). The CSF cushions, protects, and bathes the brain and spinal cord, carrying chemicals, nutrients, and wastes to and from the bloodstream.

Neurons are very specialized, and neurotransmitters perform vital functions in the normal working brain. Their absence or excess can play a major role in brain disease and behavioral disorders. A single neurotransmitter can affect other brain chemicals as well as several different subtypes of receptor cells, each located along tracts connecting different regions of the brain. Thus the same neurotransmitter can have one effect in one part of the brain and different effects in another part of the brain. Nearly all known neurotransmitters fall into one of two categories: small amine molecules (monoamines, acetylcholine, amino acids) and peptides. These are described in Table 5-1.

TABLE 5-1

NEUROTRANSMITTERS AND NEUROMODULATORS IN THE BRAIN

SUBSTANCE	LOCATION	FUNCTION
Amines
Amines are neurotransmitters that are synthesized from amino acid molecules such as tyrosine, tryptophan, and histidine. Found in various regions of the brain, amines affect learning, emotions, motor control, and other activities.
Monoamines
Norepinephrine (NE)	Derived from tyrosine, a dietary amino acid; located in brainstem (particularly locus ceruleus) Effect: can be excitatory or inhibitory	Levels fluctuate with sleep and wakefulness. Plays a role in changes in levels of attention and vigilance. Involved in attributing a rewarding value to a stimulus and in regulation of mood. Plays a role in affective and anxiety disorders. Antidepressants block reuptake of NE into presynaptic cell or inhibit monoamine oxidase from metabolizing it.
Dopamine (DA)	Derived from tyrosine, a dietary amino acid; located mostly in brainstem (particularly substantia nigra) Effect: generally excitatory	Involved in control of complex movements, motivation, and cognition and in regulating emotional responses. Many drugs of abuse (e.g., cocaine, amphetamines) cause DA release, suggesting a role in sensation of pleasure. Involved in movement disorders seen in Parkinson disease and in many of the deficits seen in schizophrenia and other forms of psychosis. Antipsychotic drugs block DA receptors in postsynaptic cells.
Serotonin (5-HT)	Derived from tryptophan, a dietary amino acid; located only in brain (particularly in raphe nuclei of brainstem) Effect: mostly inhibitory	Levels fluctuate with sleep and wakefulness, suggesting a role in arousal and modulation of general activity levels of CNS,∗ particularly onset of sleep. Plays a role in mood and probably in delusions, hallucinations, and withdrawal symptoms of schizophrenia. Involved in temperature regulation and pain-control system of body. The hallucinogenic drug LSD acts at 5-HT receptor sites. Plays a role in affective and anxiety disorders. Antidepressants block its reuptake into presynaptic cells.
Melatonin	Further synthesis of serotonin produced in pineal gland Effect: mostly inhibitory	Induces pigment-lightening effects on skin cells and regulates reproductive and immune function.
Acetylcholine	Synthesized from choline; located in brain and spinal cord but is more widespread in peripheral nervous system, particularly neuromuscular junction of skeletal muscle Effect: can have an excitatory or inhibitory effect	Plays a role in sleep-wakefulness cycle. Signals muscles to become active. Alzheimer disease is associated with degeneration in acetylcholine neurons. Myasthenia gravis (weakness of skeletal muscles) results from reduction in acetylcholine receptors.
Amino Acids
Glutamate	Found in all cells of body, where it is used to synthesize structural and functional proteins; also found in CNS, where it is stored in synaptic vesicles and used as a neurotransmitter Effect: excitatory	Implicated in schizophrenia; glutamate receptors control the opening of ion channels that allow calcium (essential to neurotransmission) to pass into nerve cells, propagating neuronal electrical impulses. Its major receptor, NMDA, helps regulate brain development. This receptor is blocked by drugs (e.g., PCP) that cause schizophrenic-like symptoms. Overexposure to glutamate is toxic to neurons and may cause cell death in stroke and Huntington disease.
Gamma-aminobutyric acid (GABA)	A glutamate derivative; most neurons of CNS have receptors Effect: major transmitter for postsynaptic inhibition on CNS	Drugs that increase GABA function, such as benzodiazepines, are used to treat anxiety and epilepsy and to induce sleep.
Histamine	Located in diencephalon, particularly hypothalamus (see Figure 5-4) Effect: can be excitatory or inhibitory	May play a role in alertness and learning. Is being investigated as potential mechanism for side effects commonly associated with psychotropic medications (weight gain, hyperlipidemia). Same substance as involved with immunological/allergic responses.
Peptides
Peptides are chains of amino acids found throughout the body. New peptides are continually being identified, with 100 neuropeptides active in the brain, but their role as neurotransmitters is not well understood. Although they appear in very low concentrations in the CNS, they are very potent. They also appear to play a “second messenger” role in neurotransmission; that is, they modulate messages of nonpeptide neurotransmitters through G protein–linked receptors.
Endorphins, enkephalins, dynorphins, and endomorphins	Widely distributed in CNS Effect: generally inhibitory	The opiates morphine and heroin bind to these endogenous opioid receptors on presynaptic neurons, blocking release of neurotransmitters and thus reducing pain.
Substance P	Spinal cord, brain, and sensory neurons associated with pain Effect: generally excitatory	Found in pain transmission pathway. Blocking release of substance P by morphine reduces pain.

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