Brain Disorders Sourcebook, 6th Ed.

Preface

About This Book

Millions of Americans and their families experience the daily challenges of living with physical, mental, or emotional difficulties that result from brain disorders caused by heredity, infection, injury, tumors, or degeneration. Someone in the United States has a stroke every 40 seconds. Every 4 minutes, someone dies of a stroke. Every year, more than 795,000 people in the United States have a stroke. About 610,000 of these are first or new strokes. An estimated 5.5 ­million Americans are affected by Alzheimer disease (AD), and the number of people living with the disease doubles every 5 years beyond age 65. Although damage to the brain may result in permanent disability, with appropriate treatment and follow-up care, many affected individuals are able to participate fully in life’s activities.

Brain Disorders Sourcebook, Sixth Edition provides readers with updated information about brain function and aging process as well as how the environment can affect brain disorders, neurological emergencies such as a brain attack (stroke) or seizure, and symptoms of brain disorders. It describes the diagnosis, treatment, and rehabilitation therapies for genetic and congenital brain disorders, brain infections, brain tumors, seizures, traumatic brain injuries (TBIs), and degenerative brain disorders such as Alzheimer disease (AD) and other dementias, Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). A glossary of terms related to brain disorders is also included along with a directory of resources for additional information.

How to Use This Book

This book is divided into parts and chapters. Parts focus on broad areas of interest. Chapters are devoted to single topics within a part.

Part 1: Brain Basics describes the human brain and how the aging process and the environment may contribute to brain disorders. It also covers how toxins affect the brain, symptoms of brain disorders, and details about identifying neurological emergencies. Facts about coma, other states of impaired consciousness, and brain death are also included.

Part 2: Diagnosing and Treating Brain Disorders covers contemporary therapies, such as the use of steroids, chemotherapy, radiation therapy, liquid biopsy, and brain surgery, and reviews typical neurological testing and procedures. Information about chemotherapy, deep brain stimulation (DBS), measurements of brain function, and brain rehabilitation is also presented.

Part 3: Genetic and Congenital Brain Disorders discusses adrenoleukodystrophy, Batten disease, and other neurological disorders that cause serious impairment and shorten life expectancy. It also reviews congenital disorders that affect brain function throughout life, but which are not always progressively debilitating. Cerebral palsy (CP), cephalic disorders, and other neurological disorders are among them.

Part 4: Brain Infections provides information about the ailments caused by viruses or parasites in the brain and related structures. These ailments, which can cause severe illness – and even death – in otherwise healthy individuals, include encephalitis, meningitis, progressive multifocal leukoencephalopathy (PML), neurosyphilis, and cysticercosis.

Part 5: Acquired and Traumatic Brain Injuries offers guidelines for identifying traumatic head injuries and offering first aid. Concussion facts are presented, as well as detailed information regarding traumatic brain injury (TBI) and tips to assist individuals and families affected by the condition are provided. Acquired (nontraumatic) brain injuries, such as cerebral aneurysms, agnosia, hydrocephalus, and stroke, are discussed in separate chapters.

Part 6: Brain Tumors describes the symptoms and treatments for primary, metastatic, pituitary, childhood and adult brain tumors as well as benign and tumor-associated brain cysts. It includes information on brain cancer statistics in the United States as well as how to deal with medication side effects, fatigue, cognitive shifts, and work-related issues.

Part 7: Degenerative Brain Disorders discusses neurological disorders that often lead to progressive deterioration of physical or mental functioning. These include Alzheimer disease (AD) and other dementias, amyotrophic lateral sclerosis (ALS), cerebellar degeneration, Creutzfeldt-Jakob disease (CJD), Friedreich ataxia (FA), Huntington disease (HD), multiple sclerosis (MS), Parkinson disease (PD), and progressive supranuclear palsy (PSP).

Part 8: Seizures and Neurological Disorders of Sleep explains sleep and how it resets the brain, as well as epileptic and nonepileptic seizure disorders, myoclonus, restless legs syndrome (RLS), and narcolepsy.

Part 9: Additional Help and Information provides a glossary of terms related to brain disorders and a directory of organizations and resources for additional information.

Bibliographic Note

This volume contains documents and excerpts from publications issued by the following U.S. government agencies: Agency for Toxic Substances and Disease Registry (ATSDR); Alzheimers.gov; Centers for Disease Control and Prevention (CDC); Child Welfare Information Gateway; Eldercare Locator; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Genetic and Rare Diseases Information Center (GARD); MedlinePlus; National Cancer Institute (NCI); National Center on Birth Defects and Developmental Disabilities (NCBDDD); Parkinson’s Disease Biomarkers Program (PDBP); National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA); National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH); News and Events; U.S. Environmental Protection Agency (EPA); U.S. Food and Drug Administration (FDA); and U.S. National Library of Medicine (NLM).

It also contains original material produced by Omnigraphics and reviewed by medical consultants.

About the Health Reference Series

The Health Reference Series is designed to provide basic medical information for patients, families, caregivers, and the general public. Each volume provides comprehensive coverage on a particular topic. This is especially important for people who may be dealing with a newly diagnosed disease or a chronic disorder in themselves or in a family member. People looking for preventive guidance, information about disease warning signs, medical statistics, and risk factors for health problems will also find answers to their questions in the Health Reference Series. The Series, however, is not intended to serve as a tool for diagnosing illness, in prescribing treatments, or as a substitute for the physician–patient relationship. All people concerned about medical symptoms or the possibility of disease are encouraged to seek professional care from an appropriate healthcare provider.

A Note about Spelling and Style

Health Reference Series editors use Stedman’s Medical Dictionary as an authority for questions related to the spelling of medical terms and The Chicago Manual of Style for questions related to grammatical structures, punctuation, and other editorial concerns. Consistent adherence is not always possible, however, because the individual volumes within the Series include many documents from a wide variety of different producers, and the editor’s primary goal is to present material from each source as accurately as is possible. This sometimes means that information in different chapters or sections may follow other guidelines and alternate spelling authorities. For example, occasionally a copyright holder may require that eponymous terms be shown in possessive forms (Crohn’s disease vs. Crohn disease) or that British spelling norms be retained (leukaemia vs. leukemia).

Medical Review

Omnigraphics contracts with a team of qualified, senior medical professionals who serve as medical consultants for the Health Reference Series. As necessary, medical consultants review reprinted and originally written material for currency and accuracy. Citations including the phrase Reviewed (month, year) indicate material reviewed by this team. Medical consultation services are provided to the Health Reference Series editors by:

Dr. Vijayalakshmi, MBBS, DGO, MD

Dr. Senthil Selvan, MBBS, DCH, MD

Dr. K. Sivanandham, MBBS, DCH, MS (Research), PhD

Health Reference Series Update Policy

The inaugural book in the Health Reference Series was the first edition of Cancer Sourcebook published in 1989. Since then, the Series has been enthusiastically received by librarians and in the medical community. In order to maintain the standard of providing high-quality health information for the layperson the editorial staff at Omnigraphics felt it was necessary to implement a policy of updating volumes when warranted.

Medical researchers have been making tremendous strides, and it is the purpose of the Health Reference Series to stay current with the most recent advances. Each decision to update a volume is made on an individual basis. Some of the considerations include how much new information is available and the feedback we receive from people who use the books. If there is a topic you would like to see added to the update list, or an area of medical concern you feel has not been adequately addressed, please write to:

Managing Editor

Health Reference Series

Omnigraphics

615 Griswold St., Ste. 520

Detroit, MI 48226

Part 1 | Brain Basics

Chapter 1 | Know Your Brain

The brain is the most complex part of the human body. This three-pound organ is the seat of intelligence, interpreter of the senses, initiator of body movement, and controller of behavior. Lying in its bony shell and washed by protective fluid, the brain is the source of all the qualities that define our humanity. The brain is the crown jewel of the human body.

For centuries, scientists and philosophers have been fascinated by the brain, but until recently they viewed the brain as nearly incomprehensible. Now, however, the brain is beginning to relinquish its secrets. Scientists have learned more about the brain in the last 10 years than in all previous centuries because of the accelerating pace of research in neurological and behavioral science and the development of new research techniques. As a result, Congress named the 1990s the Decade of the Brain.

This chapter is a basic introduction to the human brain. It may help you understand how the healthy brain works, how to keep it healthy, and what happens when the brain is diseased or dysfunctional.

The Architecture of the Brain

The brain is like a committee of experts. All the parts of the brain work together, but each part has its own special properties. The brain can be divided into three basic units: the forebrain, the midbrain, and the hindbrain.

Figure 1.1. Know Your Brain

(Source: Brain, Surveillance, Epidemiology, and End Results (SEER)

Program, National Cancer Institute (NCI).)

The hindbrain includes the upper part of the spinal cord, the brain stem, and a wrinkled ball of tissue called the cerebellum. The hindbrain controls the body’s vital functions such as respiration and heart rate. The cerebellum coordinates movement and is involved in learned rote movements. When you play the piano or hit a tennis ball you are activating the cerebellum. The uppermost part of the brainstem is the midbrain, which controls some reflex actions and is part of the circuit involved in the control of eye movements and other voluntary movements. The forebrain is the largest and most highly developed part of the human brain: it consists primarily of the cerebrum and the structures hidden beneath it.

When people see pictures of the brain it is usually the cerebrum that they notice. The cerebrum sits at the topmost part of the brain and is the source of intellectual activities. It holds your memories, allows you to plan, enables you to imagine and think. It allows you to recognize friends, read books, and play games.

The cerebrum is split into two halves (hemispheres) by a deep fissure. Despite the split, the two cerebral hemispheres communicate with each other through a thick tract of nerve fibers that lies at the base of this fissure. Although the two hemispheres seem to be mirror images of each other, they are different. For instance, the ability to form words seems to lie primarily in the left hemisphere, while the right hemisphere seems to control many abstract reasoning skills.

For some as-yet-unknown reason, nearly all of the signals from the brain to the body and vice-versa cross over on their way to and from the brain. This means that the right cerebral hemisphere primarily controls the left side of the body and the left hemisphere primarily controls the right side. When one side of the brain is damaged, the opposite side of the body is affected. For example, a stroke in the right hemisphere of the brain can leave the left arm and leg paralyzed.

The Geography of Thought

Each cerebral hemisphere can be divided into sections, or lobes, each of which specializes in different functions. To understand each lobe and its specialty we will take a tour of the cerebral hemispheres, starting with the two frontal lobes, which lie directly behind the forehead. When you plan a schedule, imagine the future, or use reasoned arguments, these two lobes do much of the work. One of the ways the frontal lobes seem to do these things is by acting as short-term storage sites, allowing one idea to be kept in mind while other ideas are considered. In the rearmost portion of each frontal lobe is a motor area, which helps control voluntary movement. A nearby place on the left frontal lobe called Broca’s area allows thoughts to be transformed into words.

When you enjoy a good meal – the taste, aroma, and texture of the food – two sections behind the frontal lobes called the parietal lobes are at work. The forward parts of these lobes, just behind the motor areas, are the primary sensory areas. These areas receive information about temperature, taste, touch, and movement from the rest of the body. Reading and arithmetic are also functions in the repertoire of each parietal lobe.

As you look at the words and pictures on this page, two areas at the back of the brain are at work. These lobes, called the occipital lobes, process images from the eyes and link that information

Figure 1.2. The Forebrain

Figure 1.3. The Midbrain

Figure 1.4. The Hindbrain

with images stored in memory. Damage to the occipital lobes can cause blindness.

The last lobes on our tour of the cerebral hemispheres are the temporal lobes, which lie in front of the visual areas and nest under the parietal and frontal lobes. Whether you appreciate symphonies or rock music, your brain responds through the activity of these lobes. At the top of each temporal lobe is an area responsible for receiving information from the ears. The underside of each temporal lobe plays a crucial role in forming and retrieving memories, including those associated with music. Other parts of this lobe seem to integrate memories and sensations of taste, sound, sight, and touch.

The Cerebral Cortex

Coating the surface of the cerebrum and the cerebellum is a vital layer of tissue the thickness of a stack of two or three dimes. It is called the cortex, from the Latin word for bark. Most of the actual information processing in the brain takes place in the cerebral cortex. When people talk about gray matter in the brain they are talking about this thin rind. The cortex is gray because nerves in this area lack the insulation that makes most other parts of the brain appear to be white. The folds in the brain add to its surface area and therefore increase the amount of gray matter and the quantity of information that can be processed.

The Inner Brain

Deep within the brain, hidden from view, lie structures that are the gatekeepers between the spinal cord and the cerebral hemispheres. These structures not only determine our emotional state, they also modify our perceptions and responses depending on that state, and allow us to initiate movements that you make without thinking about them. Like the lobes in the cerebral hemispheres, the structures described below come in pairs: each is duplicated in the opposite half of the brain.

The hypothalamus, about the size of a pearl, directs a multitude of important functions. It wakes you up in the morning, and gets

Figure 1.5. Inner Brain

the adrenaline flowing during a test or job interview. The hypothalamus is also an important emotional center, controlling the molecules that make you feel exhilarated, angry, or unhappy. Near the hypothalamus lies the thalamus, a major clearinghouse for information going to and from the spinal cord and the cerebrum.

An arching tract of nerve cells leads from the hypothalamus and the thalamus to the hippocampus. This tiny nub acts as a memory indexer – sending memories out to the appropriate part of the cerebral hemisphere for long-term storage and retrieving them when necessary. The basal ganglia (not shown) are clusters of nerve cells surrounding the thalamus. They are responsible for initiating and integrating movements. Parkinson disease, which results in tremors, rigidity, and a stiff, shuffling walk, is a disease of nerve cells that lead into the basal ganglia.

Making Connections

The brain and the rest of the nervous system are composed of many different types of cells, but the primary functional unit is a cell called the neuron. All sensations, movements, thoughts, memories, and feelings are the result of signals that pass through neurons. Neurons consist of three parts. The cell body contains

Figure 1.6. A Typical Neuron

the nucleus, where most of the molecules that the neuron needs to survive and function are manufactured. Dendrites extend out from the cell body like the branches of a tree and receive messages from other nerve cells. Signals then pass from the dendrites through the cell body and may travel away from the cell body down an axon to another neuron, a muscle cell, or cells in some other organ. The neuron is usually surrounded by many support cells. Some types of cells wrap around the axon to form an insulating sheath. This sheath can include a fatty molecule called myelin, which provides insulation for the axon and helps nerve signals travel faster and farther. Axons may be very short, such as those that carry signals from one cell in the cortex to another cell less than a hair’s width away. Or axons may be very long, such as those that carry messages from the brain all the way down the spinal cord.

Scientists have learned a great deal about neurons by studying the synapse – the place where a signal passes from the neuron to another cell. When the signal reaches the end of the axon it stimulates the release of tiny sacs. These sacs release chemicals known

Figure 1.7. Synapse

as neurotransmitters into the synapse. The neurotransmitters cross the synapse and attach to receptors on the neighboring cell. These receptors can change the properties of the receiving cell. If the receiving cell is also a neuron, the signal can continue the transmission to the next cell.

Some Key Neurotransmitters at Work

Neurotransmitters are chemicals that brain cells use to talk to each other. Some neurotransmitters make cells more active (called excitatory) while others block or dampen a cell’s activity (called inhibitory).

Acetylcholine is an excitatory neurotransmitter because it generally makes cells more excitable. It governs muscle contractions and causes glands to secrete hormones. Alzheimer disease, which initially affects memory formation, is associated with a shortage of acetylcholine.

Glutamate is a major excitatory neurotransmitter. Too much glutamate can kill or damage neurons and has been linked to disorders including Parkinson disease, stroke, seizures, and increased sensitivity to pain.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that helps control muscle activity and is an important part of the visual system. Drugs that increase GABA levels in the brain are used to treat epileptic seizures and tremors in patients with Huntington disease.

Serotonin is a neurotransmitter that constricts blood vessels and brings on sleep. It is also involved in temperature regulation. Low levels of serotonin may cause sleep problems and depression, while too much serotonin can lead to seizures.

Dopamine is an inhibitory neurotransmitter involved in mood and the control of complex movements. The loss of dopamine activity in some portions of the brain leads to the muscular rigidity of Parkinson disease. Many medications used to treat behavioral disorders work by modifying the action of dopamine in the brain.

Neurological Disorders

The brain is one of the hardest working organs in the body. When the brain is healthy it functions quickly and automatically. But when problems occur, the results can be devastating. Some 100 million Americans suffer from devastating brain disorders at some point in their lives. Some of the major types of disorders include: neurogenetic diseases (such as Huntington disease and muscular dystrophy), developmental disorders (such as cerebral palsy), degenerative diseases of adult life (such as Parkinson disease and Alzheimer disease), metabolic diseases (such as Gaucher disease), cerebrovascular diseases (such as stroke and vascular dementia), trauma (such as spinal cord and head injury), convulsive disorders (such as epilepsy), infectious diseases (such as AIDS and dementia), and brain tumors.

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This chapter includes text excerpted from Brain Basics – Know Your Brain, National Institute of Neurological Disorders and Stroke (NINDS), June 9, 2021.

Chapter 2 | Brain Development and Aging

Chapter Contents

Section 2.1—Brain Development in Childhood

Section 2.2—The Adolescent Brain

Section 2.3—The Aging Brain

Section 2.1 | Brain Development in Childhood

This section contains text excerpted from the following sources: Text under the heading Early Brain Development is excerpted from Early Brain Development and Health, National Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and Prevention (CDC), February 22, 2021; Text under the heading How the Brain Develops is excerpted from Understanding the Effects of Maltreatment on Brain Development, Child Welfare Information Gateway, U.S. Department of Health and Human Services (HHS), April 2015. Reviewed July 2021.

Early Brain Development

The early years of a child’s life are very important for later health and development. One of the main reasons is how fast the brain grows starting before birth and continuing into early childhood. Although the brain continues to develop and change into adulthood, the first 8 years can build a foundation for future learning, health, and life success.

How well a brain develops depends on many factors in addition to genes, such as:

Proper nutrition starting in pregnancy

Exposure to toxins or infections

The child’s experiences with other people and the world

Nurturing and responsive care for the child’s body and mind is the key to supporting healthy brain development. Positive or negative experiences can add up to shape a child’s development and can have lifelong effects. To nurture their child’s body and mind, parents and caregivers need support and the right resources. The right care for children, starting before birth and continuing through childhood, ensures that the child’s brain grows well and reaches its full potential.

The Importance of Early Childhood Experiences for Brain Development

Children are born ready to learn and have many skills to learn over many years. They depend on parents, family members, and other caregivers as their first teachers to develop the right skills to become independent and lead healthy and successful lives. How the brain grows is strongly affected by the child’s experiences with other people and the world. Nurturing care for the mind is critical for brain growth. Children grow and learn best in a safe environment where they are protected from neglect and from extreme or chronic stress with plenty of opportunities to play and explore.

Parents and other caregivers can support healthy brain growth by speaking to, playing with, and caring for their child. Children learn best when parents take turns when talking and playing, and build on their child’s skills and interests. Nurturing a child by understanding their needs and responding sensitively helps to protect children’s brains from stress. Speaking with children and exposing them to books, stories, and songs helps strengthen children’s language and communication, which puts them on a path towards learning and succeeding in school.

Exposure to stress and trauma can have long-term negative consequences for the child’s brain, whereas talking, reading, and playing can stimulate brain growth. Ensuring that parents, caregivers, and early childhood-care providers have the resources and skills to provide safe, stable, nurturing, and stimulating care is an important public-health goal.

When children are at risk, tracking children’s development and making sure they reach developmental milestones can help ensure that any problems are detected early and children can receive the intervention they may need.

A Healthy Start for the Brain

To learn and grow appropriately, a baby’s brain has to be healthy and protected from diseases and other risks. Promoting the development of a healthy brain can start even before pregnancy. For example, a healthy diet and the right nutrients such as sufficient folic acid will promote a healthy pregnancy and a healthy nervous system in the growing baby. Vaccinations can protect pregnant women from infections that can harm the brain of the unborn baby.

During pregnancy, the brain can be affected by many types of risks, such as by infectious diseases such as cytomegalovirus or Zika virus, by exposure to toxins, including from smoking or alcohol, or when pregnant mothers experience stress, trauma, or mental health conditions such as depression. Regular healthcare during pregnancy can help prevent complications, including premature birth, which can affect the baby’s brain. Newborn screening can detect conditions that are potentially dangerous to the child’s brain, such as phenylketonuria (PKU).

Healthy brain growth in infancy continues to depend on the right care and nutrition. Because children’s brains are still growing, they are especially vulnerable to traumatic head injuries, infections, or toxins, such as lead. Childhood vaccines, such as the measles vaccine, can protect children from dangerous complications such as swelling of the brain. Ensuring that parents and caregivers have access to healthy foods and places to live and play that are healthy and safe for their child can help them provide more nurturing care.

How the Brain Develops

What we have learned about the process of brain development helps us understand more about the roles both genetics and the environment play in our development. It appears that genetics predispose us to develop in certain ways, but our experiences, including our interactions with other people, have a significant impact on how our predispositions are expressed. In fact, research now shows that many capacities thought to be fixed at birth are actually dependent on a sequence of experiences combined with heredity. Both factors are essential for optimum development of the human brain.

Early Development

The raw material of the brain is the nerve cell, called the neuron. During fetal development, neurons are created and migrate to form the various parts of the brain. As neurons migrate, they also differentiate, or specialize, to govern specific functions in the body in response to chemical signals. This process of development occurs sequentially from the bottom-up, that is, from areas of the brain controlling the most primitive functions of the body (e.g., heart rate, breathing) to the most sophisticated functions (e.g., complex thought).

The first areas of the brain to fully develop are the brainstem and midbrain; they govern the bodily functions necessary for life, called the autonomic functions. At birth, these lower portions of the nervous system are very well developed, whereas the higher regions (cerebral cortex) are still rather primitive. Higher function brain regions involved in regulating emotions, language, and abstract thought grow rapidly in the first 3 years of life.

The Growing Child’s Brain

Brain development, or learning, is actually the process of creating, strengthening, and discarding connections among the neurons; these connections are called synapses. Synapses organize the brain by forming pathways that connect the parts of the brain governing everything we do – from breathing and sleeping to thinking and feeling. This is the essence of postnatal brain development, because, at birth, very few synapses have been formed. The synapses present at birth are primarily those that govern our bodily functions such as heart rate, breathing, eating, and sleeping.

The development of synapses occurs at an astounding rate during a child’s early years in response to that child’s experiences. At its peak, the cerebral cortex of a healthy toddler may create 2 million synapses per second. By the time children are 2 years old, their brains have approximately 100 trillion synapses, many more than they will ever need. Based on the child’s experiences, some synapses are strengthened and remain intact, but many are gradually discarded. This process of synapse elimination – or pruning – is a normal part of development. By the time children reach adolescence, about half of their synapses have been discarded, leaving the number they will have for most of the rest of their lives.

Another important process that takes place in the developing brain is myelination. Myelin is the white fatty tissue that forms a sheath to insulate mature brain cells, thus ensuring clear transmission of neurotransmitters across synapses. Young children process information slowly because their brain cells lack the myelin necessary for fast, clear nerve impulse transmission. Like other neuronal growth processes, myelination begins in the primary motor and sensory areas (the brain stem and cortex) and gradually progresses to the higher-order regions that control thought, memories, and feelings. Also, like other neuronal growth processes, a child’s experiences affect the rate and growth of myelination, which continues into young adulthood.

By 3 years of age, a baby’s brain has reached almost 90 percent of its adult size. The growth in each region of the brain largely depends on receiving stimulation, which spurs activity in that region. This stimulation provides the foundation for learning.

Responding to Stress

We all experience different types of stress throughout our lives. The type of stress and the timing of that stress determine whether and how there is an impact on the brain. The National Scientific Council on the Developing Child (2014) outlines three classifications of stress:

Positive stress is moderate, brief, and generally a normal part of life (e.g., entering a new child care setting). Learning to adjust to this type of stress is an essential component of healthy development.

Tolerable stress includes events that have the potential to alter the developing brain negatively, but which occur infrequently and give the brain time to recover (e.g., the death of a loved one).

Toxic stress includes strong, frequent, and prolonged activation of the body’s stress response system (e.g., chronic neglect).

Healthy responses to typical life stressors (i.e., positive and tolerable stress events) are very complex and may change depending on individual and environmental characteristics, such as genetics, the presence of a sensitive and responsive caregiver, and past experiences. A healthy stress response involves a variety of hormone and neurochemical systems throughout the body, including the sympathetic-adrenomedullary (SAM) system, which produces adrenaline, and the hypothalamicpituitary-adrenocortical (HPA) system, which produces cortisol. Increases in adrenaline help the body engage energy stores and alter blood flow. Increases in cortisol also help the body engage energy stores and also can enhance certain types of memory and activate immune responses. In a healthy stress response, the hormonal levels will return to normal after the stressful experience has passed.

Section 2.2 | The Adolescent Brain

This section contains text excerpted from the following sources: Text under the heading Adolescent Brain Development is excerpted from Understanding the Effects of Maltreatment on Brain Development, Child Welfare Information Gateway, U.S. Department of Health and Human Services (HHS), April 2015. Reviewed July 2021; Text beginning with the heading The Changing Brain and Behavior in Teens is excerpted from The Teen Brain: Still under Construction, National Institute of Mental Health (NIMH), July 28, 2011. Reviewed July 2021.

Adolescent Brain Development

Studies using MRI techniques show that the brain continues to grow and develop into young adulthood (at least to the mid twenties). White matter, or brain tissue, volume has been shown to increase in adults as old as 32. Right before puberty, adolescent brains experience a growth spurt that occurs mainly in the frontal lobe, which is the area that governs planning, impulse control, and reasoning. During the teenage years, the brain goes through a process of pruning synapses – somewhat like the infant and toddler brain – and also sees an increase in white matter and changes to neurotransmitter systems. As the teenager grows into young adulthood, the brain develops more myelin to insulate the nerve fibers and speed neural processing, and this myelination occurs last in the frontal lobe. MRI comparisons between the brains of teenagers and the brains of young adults have shown that most of the brain areas were the same – that is, the teenage brain had reached maturity in the areas that govern such abilities as speech and sensory capabilities.

The major difference was the immaturity of the teenage brain in the frontal lobe and in the myelination of that area.

Normal puberty and adolescence lead to the maturation of a physical body, but the brain lags behind in development, especially in the areas that allow teenagers to reason and think logically. Most teenagers act impulsively at times, using a lower area of their brains – their gut reaction – because their frontal lobes are not yet mature. Impulsive behavior, poor decisions, and increased risk-taking are all part of the normal teenage experience. Another change that happens during adolescence is the growth and transformation of the limbic system, which is responsible for our emotions. Teenagers may rely on their more primitive limbic system in interpreting emotions and reacting since they lack the more mature cortex that can override the limbic response.

The Changing Brain and Behavior in Teens

In teens, the parts of the brain involved in emotional responses are fully online, or even more active than in adults, while the parts of the brain involved in keeping emotional, impulsive responses in check are still reaching maturity. Such a changing balance might provide clues to a youthful appetite for novelty, and a tendency to act on impulse – without regard for risk.

While much is being learned about the teen brain, it is not yet possible to know to what extent a particular behavior or ability is the result of a feature of brain structure – or a change in brain structure. Changes in the brain take place in the context of many other factors, among them, inborn traits, personal history, family, friends, community, and culture.

The Adolescent and Adult Brain

It is not surprising that the behavior of adolescents would be a study in change, since the brain itself is changing in such striking ways. Scientists emphasize that the fact that the teen brain is in transition does not mean it is somehow not up to par. It is different from both a child’s and an adult’s in ways that may equip youth to make the transition from dependence to independence. The capacity for learning at this age, an expanding social life, and a taste for exploration and limit testing may all, to some extent, be reflections of age-related biology.

Understanding the changes taking place in the brain at this age presents an opportunity to intervene early in mental illnesses that have their onset at this age. Research findings on the brain may also serve to help adults understand the importance of creating an environment in which teens can explore and experiment while helping them avoid behavior that is destructive to themselves and others.

Section 2.3 | The Aging Brain

This section contains text excerpted from the following sources: Text under the heading How the Aging Brain Affects Thinking is excerpted from How the Aging Brain Affects Thinking, National Institute on Aging (NIA), National Institutes of Health (NIH), October 19, 2020; Text beginning with the heading Potential Threats to Brain Health and Preventing It is excerpted from Brain Health You Can Make a Difference, Eldercare Locator, Administration for Community Living (ACL), November 21, 2014. Reviewed July 2021.

How the Aging Brain Affects Thinking

The brain controls many aspects of thinking – remembering, planning, and organizing, making decisions, and much more. These cognitive abilities affect how well we do everyday tasks and whether we can live independently.

Some changes in thinking are common as people get older. For example, older adults may have:

Be slower to find words and recall names

Find they have more problems with multitasking

Experience mild decreases in the ability to pay attention

Aging may also bring positive cognitive changes. For example, many studies have shown that older adults have more extensive vocabularies and greater knowledge of the depth of meaning of words than younger adults. Older adults may also have learned from a lifetime of accumulated knowledge and experiences. Whether and how older adults apply this accumulated knowledge, and how the brain changes as a result, is an area of active exploration by researchers.

Despite the changes in cognition that may come with age, older adults can still do many of the things they have enjoyed their whole lives. Research shows that older adults can still:

Learn new skills

Form new memories

Improve vocabulary and language skills

Changes in the Aging Brain

As a person gets older, changes occur in all parts of the body, including the brain.

Certain parts of the brain shrink, especially those important to learning and other complex mental activities.

In certain brain regions, communication between neurons (nerve cells) may not be as effective.

Blood flow in the brain may decrease.

Inflammation, which occurs when the body responds to an injury or disease, may increase.

These changes in the brain can affect mental function, even in healthy older people. For example, some older adults may find that they do not do as well as younger individuals on complex memory or learning tests. However, if given enough time to learn a new task, they usually perform just as well. Needing that extra time is normal as we age. There is growing evidence that the brain maintains the ability to change and adapt so that people can manage new challenges and tasks as they age.

Potential Threats to Brain Health and Preventing It

Health Conditions

Some health conditions can negatively affect your brain. Heart disease, high blood pressure and diabetes can alter or damage blood vessels throughout your body, including the brain. Alzheimer disease and other types of dementia also harm the brain. While no one knows how to prevent dementia, many approaches that are good for your health in other ways, including engaging in exercise and eating a healthy diet, are being tested.

Medicines

Some medications and certain combinations of drugs can affect your thinking and the way your brain works. Older adults taking medications should be particularly careful when consuming alcohol, as drugs may interact negatively with it.

Alcohol

Drinking alcohol can slow or impair communication among your brain cells. This can cause slurred speech, a fuzzy memory, drowsiness and dizziness; it can also lead to long-term difficulties with your balance, memory, coordination and body temperature.

Smoking

The risks associated with smoking are heart attacks, stroke and lung disease.

Brain Injury

Older adults are at higher risk of falling and other accidents that can cause brain injury

Action You Can Take to Help Protect Your Brain

Take Charge

Get recommended health screenings regularly.

Manage health conditions, such as diabetes, high blood pressure and high cholesterol.

Be sure to talk with your doctor or pharmacist about the medications you take and any possible side effects on memory, sleep and how your brain works.

Eat Right

Try to maintain a balanced diet of fruits and vegetables, whole grains, lean meats (including fish and poultry) and low-fat or nonfat dairy products. Monitor your intake of solid fat, sugar and salt, and eat proper portion sizes.

Get Moving

Being physically active may help reduce the risk of conditions that can harm brain health, such as diabetes, heart disease, depression and stroke; it may also help improve connections among your brain cells. Older adults should get at least 150 minutes of exercise each week.

Drink Moderately, If at All

Staying away from alcohol can reverse some negative changes related to brain health.

Do not Smoke

Quitting smoking at any age will be beneficial to the health of your mind and body. Nonsmokers have a lower risk of heart attacks, stroke and lung diseases, as well as increased blood circulation.

Be Safe

To reduce the risk of falling, exercise to improve balance and coordination, take a falls prevention class, and make your home safer.

Think and Connect

Keep your mind active by doing mentally stimulating activities such as reading, playing games, learning new things, teaching or taking a class and being social. Older adults who remain active and engaged with others by doing activities such as volunteering report being happier and healthier overall.

Taking the First Step

You can start to support your brain health with some small, first steps, and build from there.

Begin an exercise routine, such as a daily walk, with the goal of increasing the amount of time and speed.

Add an extra serving of fruit and vegetables each day.

Make an appointment for a health screening or a physical exam.

Seek out volunteer opportunities that interest you.

Sign up for a class or program at your community college or community center.

Chapter 3 | How Toxins Affect the Brain

Chapter Contents

Section 3.1—Neurotoxicity

Section 3.2—Impact of Drug Abuse and Addiction on the Brain

Section 3.3—Mercury and Neurodevelopment

Section 3.4—Dangers of Lead Exposure

Section 3.5—Manganese and Brain Damage

Section 3.1 | Neurotoxicity

This section includes text excerpted from Neurotoxicity, U.S. National Library of Medicine (NLM), March 4, 2021.

The nervous system is very complex and toxins can act at many different points in this complex system. The focus of this section is to provide a basic overview of how the nervous system works and how neurotoxins affect it. Due to the complexity of these topics, this section does not include extensive details related to the anatomy and physiology of the nervous system or the many neurotoxins in our environment and the subtle ways they can damage the nervous system or interfere with its functions.

Since the nervous system innervates all areas of the body, some toxic effects may be quite specific and others generalized depending upon where in the nervous system the toxin exerts its effect.

All the functions of the nervous system are potentially vulnerable to the actions of toxicants.

Toxic Damage to Nervous System

The nervous system is quite vulnerable to toxins since chemicals interacting with neurons can change the critical voltages, which must be carefully maintained. However, the nervous system has defense mechanisms that can protect it from toxins.

Most of the CNS is protected by an anatomical barrier between the neurons and blood vessels, known as the blood-brain barrier. It is protected from some toxin exposures by tightening junctions between endothelial cells of the blood vessels in the CNS and having astrocytes surround the blood vessels. This prevents the diffusion of chemicals out of the blood vessels and into the intracellular fluid except for small, lipid-soluble, nonpolar molecules. Specific transport mechanisms exist to transport essential nutrients (such as glucose and amino acids and ions) into the brain. Another defense mechanism within the brain to counter chemicals that pass through the vascular barrier is the presence of metabolizing enzymes. Certain detoxifying enzymes, such as monoamine oxidase, can biotransform many chemicals to less toxic forms as soon as they enter the intercellular fluid.

The basic types of changes due to toxins can be divided into three categories – sensory; motor; and interneuronal – depending on the type of damage sustained.

Damage can occur to sensory receptors and sensory neurons, which can affect the basic senses of pressure, temperature, vision, hearing, taste, smell, touch, and pain.

For example, heavy metal poisoning (especially lead and mercury) can cause deafness and loss of vision.

Several chemicals including inorganic salts and organophosphorus compounds can cause a loss of sensory functions.

Damage to motor neurons can cause muscular weakness and paralysis.

Isonicotinic hydrazide (used to treat tuberculosis) can cause such damage.

Interneuronal damage can cause learning deficiencies, loss of memory, incoordination, and emotional conditions.

Low levels of inorganic mercury and carbon monoxide can cause depression and loss of memory.

Mechanisms for Toxic Damage to the Nervous System

Toxic damage to the nervous system occurs by the following basic mechanisms:

Death of Neurons and Glial Cells

The most common cause of death of neurons and glial cells is anoxia, an inadequate oxygen supply to the cells or their inability to utilize oxygen. Anoxia may result from the blood’s decreased ability to provide oxygen to the tissues (impaired hemoglobin or decreased circulation) or from the cells unable to utilize oxygen.

For example, carbon monoxide and sodium nitrite can bind to hemoglobin preventing the blood from being able to transport oxygen to the tissues.

Hydrogen cyanide and hydrogen sulfide can penetrate the blood-brain barrier and is rapidly taken up by neurons and glial cells.

Another example is sodium fluoroacetate (commonly known as Compound 1080, a rodent pesticide) which inhibits a cellular enzyme.

Those chemicals interfere with cellular metabolism and prevent nerve cells from being able to utilize oxygen. This is called histotoxic anoxia.

Neurons are among the most sensitive cells in the body to inadequate oxygenation. Lowered oxygen for only a few minutes is sufficient to cause irreparable changes leading to the death of neurons.

Several other neurotoxins directly damage or kill neurons, including:

Lead

Mercury

Some halogenated industrial solvents including methanol (wood alcohol)

Toluene

Trimethyltin polybrominated diphenyl ethers (PBDEs)

While some neurotoxic agents affect neurons throughout the body, others are quite selective.

For example, methanol specifically affects the optic nerve, retina, and related ganglion cells while trimethyltin kills neurons in the hippocampus, a region of the cerebrum.

Other agents can degrade neuronal cell function by diminishing its ability to synthesize protein, which is required for the normal function of the neuron.

Organomercury compounds exert their toxic effect in this manner.

With some toxins, only a portion of the neuron is affected. If the cell body is killed, the entire neuron will die. Some toxins can cause death or loss of only a portion of the dendrites or axon while the cell itself survives but with diminished or total loss of function. Commonly axons begin to die at the very distal end of the axon with necrosis slowly progressing toward the cell body. This is referred to as dying-back neuropathy.

Some organophosphate chemicals (including some pesticides) cause this distal axonopathy. The mechanism for the dying back is not clear but may be related to the inhibition of an enzyme (neurotoxic esterase) within the axon.

Other well-known chemicals can cause distal axonopathy include ethanol, carbon disulfide, arsenic, ethylene glycol (in antifreeze), and acrylamide.

Interference with Electrical Transmission

There are two basic ways that a foreign chemical can interrupt or interfere with the propagation of the electrical potential (impulse) down the axon to the synaptic junction:

To interfere with the movement of the action potential down the intact axon

To cause structural damage to the axon or its myelin coating. Without an intact axon, transmission of the electrical potential is not possible.

Agents that can block or interfere with the sodium and potassium channels and sodium-potassium pump cause interruption of the propagation of the electrical potential. This will weaken, slow, or completely interrupt the movement of the electrical potential. Many potent neurotoxins exert their toxicity by this mechanism.

Tetrodotoxin (a toxin in frogs, pufferfish, and other invertebrates) and saxitoxin (a cause of shellfish poisoning) blocks sodium channels. Batrachotoxin (a toxin in South American frogs used as arrow poison) and some pesticides (DDT and pyrethroids) increases the permeability of the neuron membrane preventing closure of sodium channels which leads to repetitive firing of the electrical charge and an exaggerated impulse.

A number of chemicals can cause demyelination. Many axons (especially in the PNS) are wrapped with a protective myelin sheath that acts as insulation and restricts the electrical impulse within the axon. Agents that selectively damage these coverings disrupt or interrupt the conduction of high-speed neuronal impulses. Loss of a portion of the myelin can allow the electrical impulse to leak out into the tissue surrounding the neuron so that the pulse does not reach the synapse with the intended intensity.

In some diseases, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), the myelin is lost, causing paralysis and loss of sensory and motor function.

A number of chemicals can cause demyelination:

Diphtheria toxin causes loss of myelin by interfering with the production of protein by the Schwann cells that produce and maintain myelin in the PNS.

Triethyltin (used as a biocide, preservative, and polymer stabilizer) interrupts the myelin sheath around peripheral nerves.

Lead causes loss of myelin primarily around peripheral motor axons.

Interference with Chemical Neurotransmission

Synaptic dysfunction is a common mechanism for the toxicity of a wide variety of chemicals. There are two types of synapses: those between two neurons (axon of one neuron and dendrites of another) and those between a neuron and a muscle cell or gland. The basic mechanism for the chemical transmission is the same. The major difference is that the neurotransmitting chemical between a neuron and muscle cell is acetylcholine whereas there are several other types of neurotransmitting chemicals involved between neurons, depending on where in the nervous system the synapse is located.

There are four basic steps involved in neurotransmission at the synapse:

Synthesis and storage of neurotransmitter (synaptic knob of axon)

Release of the neurotransmitter (synaptic knob with movement across synaptic cleft)

Receptor activation (effector membrane)

Inactivation of the transmitter (enzyme breaks down neurotransmitter stopping induction of action potential)

The arrival of the action potential at the synaptic knob initiates a series of events culminating in the release of the chemical neurotransmitter from its storage depots in vesicles. After the neurotransmitter diffuses across the synaptic cleft, it complexes with a receptor (membrane-bound macromolecule) on the postsynaptic side. This binding causes an ion channel to open, changing the membrane potential of the postsynaptic neuron or muscle or gland. This starts the process of impulse formation or action potential in the next neuron or receptor cell. However, unless this receptor-transmitter complex is inactivated, the channel remains open with continued pulsing. Thus, the transmitter action must be terminated. Specific enzymes that can break the bond and return the receptor-membrane to its resting state do this.

Drugs and environmental chemicals can interact at specific points in this process to change the neurotransmission. Depending on where and how the xenobiotics act, the result may be either an increase or a decrease in neurotransmission. Many drugs (such as tranquilizers, sedatives, stimulants, beta-blockers) are used to correct imbalances to neurotransmissions (such as occurs in depression, anxiety, and cardiac muscular weakness). The mode of action of some analgesics is to block receptors, which prevent transmission of pain sensations to the brain.

Exposure to environmental chemicals that can perturb neurotransmission is a very important area of toxicology. Generally, neurotoxins affecting neurotransmission act to:

Increase or decrease the release of a neurotransmitter at the presynaptic membrane.

Block receptors at the postsynaptic membrane.

Modify the inactivation of the neurotransmitter.

This is a list of only a few examples of neurotoxins to show the range of mechanisms:

α-Bungarotoxin (a potent venom of elapid snakes) prevents the release of neurotransmitters.

Scorpion venom potentiates the release of a neurotransmitter (acetylcholine).

Black widow spider venom causes an explosive release of neurotransmitters.

Botulinum toxin blocks the release of acetylcholine at neuromuscular junctions.

Atropine blocks acetylcholine receptors.

Strychnine inhibits the neurotransmitter glycine at postsynaptic sites resulting in an increased level of neuronal excitability in the CNS.

Nicotine binds to certain cholinergic receptors.

A particularly important type of neurotoxicity is the inhibition of acetylcholinesterase. The specific function of acetylcholinesterase is to stop the action of acetylcholine once it has bound to a receptor and initiated the action potential in the second nerve or at the neuro-muscular or glandular junction. If the acetylcholine-receptor complex is not inactivated, continual stimulation will result leading to paralysis and death.

Many commonly used chemicals, especially organophosphate and carbamate pesticides, poison mammals by this mechanism.

The major military nerve gases are also cholinesterase inhibitors.

Section 3.2 | Impact of Drug Abuse and Addiction on the Brain

This section includes text excerpted from Understanding Drug Use and Addiction Drug Facts, National Institute on Drug Abuse (NIDA), June 2018.

Many people do not understand why or how other people become addicted to drugs. They may mistakenly think that those who use drugs lack moral principles or willpower and that they could stop their drug use simply by choosing to. In reality, drug addiction is a complex disease, and quitting usually takes more than good intentions or a strong will. Drugs change the brain in ways that make quitting hard, even for those who want to. Fortunately, researchers know more than ever about how drugs affect the brain and have found