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A Practical Family Reference from Medical Experts

by Floyd E. Bloom, M.D.;
M. Flint Beal, M.D.;
and David J. Kupfer, M.D.;
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Development of the fetal brain: These five drawings chart the development of the fetal brain. They are not to scale—at 4 weeks, the fetal brain is not much bigger than a grain of salt; at 7 weeks, it measures barely a quarter inch. As the brain grows, it begins to develop the characteristic folds as it expands to fill the cranium. (images credit: Kathryn Born)

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MILESTONES IN DEVELOPMENT

Scientists have studied prenatal brain growth in two main ways. By examining fetuses that did not survive until birth, they learned about the anatomical changes that take place at different stages of human development. Researchers have also conducted experiments in animals, particularly in monkeys (whose brains most resemble those of people), to learn more about normal development and what can disrupt it. Today it is also possible to use imaging technology, while a child is still a fetus in the womb, to examine the developing brain.

With these methods, we have a good picture of how a fetus normally develops. It takes about 38 weeks for a single fertilized egg to grow into a baby. Pinpointing the exact date of conception is often difficult, however, so pregnancy is most often said to last for 40 weeks from the date of the woman’s last period. The timeline below shows how your baby’s brain develops during the various months of pregnancy.

MONTH 1

BRAIN: A preliminary structure known as the neural tube forms. Part of this eventually becomes the spinal cord, and the other part the brain.

OTHER MILESTONES: All major organs are forming by the third week of development, and the heart begins to beat.

MONTH 2

BRAIN: The major structures of the brain begin to form, including the cerebral cortex. As the brain grows, the embryo’s head begins to look more human.

OTHER MILESTONES: All major organs have now developed. The eyes, ears, nose, and mouth begin to take shape.

MONTH 3

BRAIN: The brain continues to grow new cells and make connections between those already in place. The fetus develops physical reflexes.

OTHER MILESTONES: The eyes are in place, and eyelids are beginning to form. The fetus cannot control its movements, but it can react to stimuli by moving its arms and kicking.

MONTH 4

BRAIN: Parts of the brain begin to receive signals from the developing ears and eyes. The fetus can detect bright lights and hear sounds like its mother’s voice, although it will not yet know how to interpret them. As facial muscles develop along with the brain, the fetus can squint and frown.

OTHER MILESTONES: The lungs begin to function, although the fetus still receives its oxygen through the placenta. Taste buds form on the tongue. Eyebrows and eyelashes grow.

MONTH 5

BRAIN: As the brain makes more and more connections, the fetus begins to control its movements, turning and stretching, perhaps even somersaulting. The fetus also begins to react to sounds outside the mother, such as music.

OTHER MILESTONES: The sex organs become visible on an ultrasound. The beginning of an immune system emerges.

MONTH 6

BRAIN: The cerebral cortex is now the largest part of the brain and has started to separate into lobes. As this part of the brain develops, a primitive type of memory and conscious behavior emerge. You may notice the fetus reacts more to some noises and music than others. Some experts believe the fetus will remember music and voices “heard” at this stage and unconsciously react with comfort to them after birth.

OTHER MILESTONES: The facial features are so developed that the fetus looks almost like a newborn. All muscles are in place, and the bones begin to harden.

MONTH 7

BRAIN: The once-smooth fetal brain has begun to form the grooves and indentations typical of a more mature brain. An electroencephalogram (EEG) can detect fetal brain waves. Myelin begins to form a protective sheath around nerves from the brain, like insulation keeping wires from crossing; this sheath enhances communication among nerve cells.

OTHER MILESTONES: The fetus gains weight as it builds up fat stores that will later help to maintain temperature. Eyelids open, the fetus begins to “see” inside the womb. It may swallow or suck its thumb.

MONTH 8

BRAIN: The auditory cortex, the visual cortex, and Broca’s area have begun to function. The fetus is thus developing a primitive ability to interpret sights and sounds and distinguish language.

OTHER MILESTONES: All organs except the lungs have now matured. As the eyes develop further, the fetus can begin to focus. The fetus has grown so large that it can no longer easily move about.

MONTH 9

BRAIN: The brain continues to grow, and by this time most of the neurons your child will ever have are in place. Just before birth, the brain is one fourth the size and weight of an adult brain.

OTHER MILESTONES: The fetus gets into position for birth, usually with its head facing downward toward the mother’s cervix. The lungs mature. The immune system continues to develop.

HOW TO FEED DEVELOPMENT

When it comes to nutrition and the pregnant woman, “experts” abound and the advice is often contradictory. Eat for two. Eat for your baby. Eat for yourself. Give in to your cravings for pickles and ice cream. Don’t give in to your cravings. Give up coffee and switch to herbal tea. Don’t drink herbal tea.

What’s a woman to do? First of all, relax. The best advice nutritionists give pregnant women is remarkably similar to the advice they give all of us: eat a balanced diet low in fat, heavier in carbohydrates, and rich in fruits and vegetables. Of course, there are a few cautions for pregnant women based on the needs of the developing fetus. The best thing you can do is talk with your obstetrician about your particular nutritional requirements. Many physicians recommend that pregnant women take a multivitamin or a special “prenatal” vitamin each day to supplement their diets.

Here are a few guidelines for eating well during pregnancy:

■ Add 300 to 800 calories per day to your diet to provide the extra energy your body needs. The amount your physician recommends will depend on your weight and activity level. A woman who weighs 125 pounds (56 kg), for instance, might normally consume 2,000 calories a day before pregnancy but should increase that by about 300 calories a day while pregnant.

■ Fresh food is best when it comes to nutrients; frozen foods are next best.

■ Protein is essential throughout pregnancy. Your baby’s vital organs all develop during the first trimester, but the brain continues to grow in spurts throughout pregnancy (and even after birth). All this growth requires energy, so your need for protein increases by one third when you are pregnant. Aim for six to seven ounces (200 g) of protein-containing foods per day. The best sources are cheese, eggs, fish, meat, milk, and poultry (all animal sources, which also provide amino acids that you and your developing baby need). But the FDA recommends that pregnant women not eat shark, swordfish, king mackerel, or tilefish, as they may contain enough mercury to harm your baby’s brain.

■ Make sure you get enough vitamin D and calcium in your diet (either through dairy products or supplements), since these build your baby’s bones and teeth. Aim for four glasses of milk, or 1,200 to 1,300 mg of calcium and 400 IU of vitamin D per day.

■ Drink plenty of fluids. While you are pregnant, the volume of blood circulating in your body (and to your fetus) increases by almost 50 percent. Since water is a component of blood (as well as every other part of our bodies), getting enough to drink is important. Aim for at least eight glasses of water or fruit juice per day.

■ Make sure you get enough iron in your diet. This helps build red blood cells, which supply oxygen to your body and the developing fetus. Since iron supplements may cause stomach irritation (and thus worsen morning sickness), some women prefer to postpone taking them until the second trimester. That’s fine, since maintaining sufficient blood iron levels is most important in the latter part of a pregnancy. Aim for 48 to 78 mg of iron per day, from a supplement or through foods like dried beans, liver, and meat.

■ Many herbal teas are fine, but avoid herbal supplements. To be on the safe side, drink only those herbal teas that contain ingredients naturally found in your diet. These include apple, orange, and mint tea. Some experts advise staying away from ingredients such as chamomile and hibiscus, whose effects during pregnancy are not known.

WHAT TO AVOID (OR REDUCE)

Fetal development, and especially brain development, is full of peril and promise. With millions of cells multiplying each day, and the brain building itself inside out, much can go wrong. Fortunately, the brain has its own built-in repair systems. But if you ingest certain drugs and substances during pregnancy, not only do you increase the risk that a developmental mistake will happen, but you also may prevent the fetal repair systems from working properly. Listed below are some substances to avoid while pregnant.

ALCOHOL: It is best to avoid alcohol altogether while pregnant, and to give up drinking if you are trying to conceive. Alcohol can interfere with brain development. It sometimes causes fetal alcohol syndrome, which involves central nervous system abnormalities, mental retardation, and stunted growth. Because alcohol in the mother’s bloodstream passes into the placenta so easily, the developing fetus receives almost as much from a drink as its mother does. Some experts, in fact, estimate that 2.5 percent of all birth defects are caused by alcohol. If you had a few drinks before discovering you were pregnant, it is likely that any damage to the fetus will be overcome as long as you stop drinking. But speak with your physician if you have any concerns.

DIETARY SUPPLEMENTS: Herbal and dietary supplements, often sold in health food stores and increasingly showing up in grocery stores as well, are not regulated by the U.S. Food and Drug Administration. For the most part, physicians have not studied their use in pregnant women. Most experts therefore recommend avoiding such supplements altogether during pregnancy.

ILLEGAL DRUGS: Substances such as cocaine, heroin, and marijuana can have a devastating effect on fetal development and should be avoided completely during pregnancy. These drugs wreak havoc with brain development and can result in premature delivery, behavioral problems, and learning disorders.

MEDICATIONS: If at all possible, it is best to avoid both over-the-counter and prescription medications during pregnancy, and especially during the first trimester, when your baby’s vital organs are developing. Even some medications you might consider harmless, such as some cough medicines, contain alcohol. If you have a medical condition requiring medication, talk the issue over with your physician. He or she might be able to recommend a strategy that will balance your needs with those of your developing child.

SMOKING: Smoking any form of tobacco can badly affect the fetus’s physical development and perhaps brain development. Smoking has been linked to low weight at birth and a greater risk of miscarriage. Some studies (although the evidence is less conclusive here) have reported that a mother’s smoking may contribute to learning difficulties and behavioral problems later on in her child’s life. Certainly the safest strategy is not to smoke; if you cannot give up the habit, at least cut back as much as possible.

WHY FOLIC ACID COUNTS

Chances are, you have heard about folic acid. This B vitamin, once overlooked, has burst into public awareness in the past ten years or so. And if you are concerned with your child’s developing nervous system, it bears special attention.

In 1989 researchers reported that folic acid deficiency could result in devastating brain and spinal cord abnormalities. These include spina bifida, in which the spinal cord develops outside the vertebrae (C9), and anencephaly, where most of the brain fails to develop. Each year, about one baby out of a thousand suffers some type of neurological damage caused by folic acid deficiency. Fortunately, studies have reported that folic acid supplements can decrease the risk of neurological birth defects by as much as 70 percent.

Why is folic acid so important? It is essential for forming new cells because it promotes enzymes that help build genetic material. Folic acid is thus most important when cells are multiplying rapidly—as in early fetal development. Although a mother-to-be needs adequate folic acid throughout her pregnancy, the vitamin is essential in the first few weeks, when the embryo’s neural groove closes to form the neural tube and the brain begins to develop. Since a woman may not even realize she is pregnant during this time, most experts recommend that all women of childbearing age make sure they get enough folic acid.

You can obtain folic acid naturally by eating fortified cereals and green leafy vegetables. Or you can take a supplement. An expectant mother should aim for at least .4 mg (400 mcg) of folic acid a day during the first trimester and, ideally, throughout pregnancy. Some experts recommend as much as 1 mg per day. Check with your physician to determine the best strategy for you.

PRENATAL TESTS AND THE BRAIN

ULTRASOUND is a standard test performed on almost all pregnant women in this country because it reveals a great deal, is not invasive, and has minimal risk of complications. As its name implies, ultrasound uses high-frequency sound waves to produce a picture of the developing fetus. It is generally performed twice during a woman’s pregnancy: first between the eleventh and thirteenth weeks, and then again between the eighteenth and twentieth weeks.

The images generated by an ultrasound reader may appear blurry to you at first, but a trained technician can help identify the head, arms, and legs of a developing fetus. This test helps a physician check how many babies a woman might have, the sex of each fetus, and overall growth and development. For parents, ultrasound provides the first glimpse of the fetus and a chance to listen to its heartbeat. Although most ultrasound scans reveal nothing out of the ordinary, these tests can detect abnormalities such as spina bifida (where the spinal cord has not closed properly; C9) and anencephaly (where most of the brain fails to develop). Further tests, such as those described below, are needed to confirm these diagnoses.

The NUCHAL TRANSLUCENCY SCAN, a form of ultrasound, examines the fetus to see if it has excess fluid between its skin and the underlying tissue along its back. Such excess fluid could be a sign that the fetus has Down’s syndrome or certain inherited heart abnormalities. The diagnosis is confirmed by amniocentesis. The test is usually done between the eleventh and fourteenth weeks of pregnancy.

The ALPHA-FETOPROTEIN (AFP) test is usually performed between the sixteenth and eighteenth weeks of pregnancy. High AFP levels in the mother’s blood may be a sign that the fetus has hydrocephalus or spina bifida. Low levels of this blood chemical may signal Down’s syndrome. But the screening is inexact and must be confirmed with another test.

SERUM SCREENING measures blood levels of AFP, estriol, and human chorionic gonadotropin. It provides a rough estimate of how likely it is that a mother might give birth to a baby with Down’s syndrome. The test, generally done at the sixteenth week of pregnancy, requires further confirmation by amniocentesis.

AMNIOCENTESIS is usually performed only after a screening test has identified a possible chromosomal abnormality in the developing fetus, or if a woman is older than 35 and therefore more at risk for conceiving a baby with Down’s syndrome. Amniocentesis can detect abnormalities with greater accuracy than other tests. It also carries a small risk of causing miscarriage, which is why the test is performed only when its results might affect a couple’s decision about whether to continue the pregnancy.

An amniocentesis begins with taking an ultrasound image of the fetus to determine its location. A physician then inserts a thin needle through a woman’s abdomen into her uterus to extract a small sample of the amniotic fluid surrounding the fetus. This fluid contains fetal cells that can be cultured and tested to detect any abnormalities. Amniocentesis cannot be performed before the sixteenth week of pregnancy, and results usually take two to three weeks, so waiting for the test or the results can be anxious periods for parents.

CHORIONIC VILLUS SAMPLING (CVS) also detects chromosomal abnormalities, but in a way that eventually allows cells to be tested for specific genes as well. In this procedure, a physician takes a tissue sample from the placenta and analyzes it. (To reach the uterus, the doctor may insert a needle into the abdomen or insert a catheter into the vagina and through the cervix.) This test can be done earlier than amniocentesis (generally between the tenth and twelfth weeks of pregnancy). The results are also faster: physicians can offer an initial diagnosis within a day or two, and confirmation within seven days. If a woman decides to have an abortion after learning the results of the test, it can thus be done earlier, which is safer for her. As with amniocentesis, there is a small chance this test might result in miscarriage, so it is performed only on women with a family history of certain disorders, or those who are 35 and older.

BOY BRAIN OR GIRL BRAIN?

Is it a boy or a girl? This is probably one of the first questions expectant parents are asked, or may ask themselves. But when it comes to the brain, it may not matter all that much. Certainly there are both anatomical and hormonal differences between male and female bodies, and these differences begin quite early in development. Some researchers say that there are also differences in the way the sexes think and behave, but not everyone agrees on this. Other scientists point out that most differences in ability emerge after adolescence, suggesting that either hormones or the different socialization of boys and girls may play a role. And they cite recent studies that show that men and women differ only in narrowly defined skills, such as the visual-spatial task of determining how a flat paper with perforations will look when it is folded. With broader challenges, of the sort that come up in daily life, the differences disappear. For instance, men and women usually differ on a test of verbal fluency: coming up with as many words as possible in a given category. They score the same, however, on tests of vocabulary and reading comprehension. The natural differences between male and female brains are so subtle, it seems, that people usually compensate for them.

At the anatomical level, the brains of men and women look remarkably alike. Neuroanatomists have so far identified only four structures that differ in any way:

■ The CORPUS CALLOSUM, a bridge between the left and right hemispheres, is larger in women than in men, according to some studies but not others.

■ The ANTERIOR COMMISSURE, another structure that connects the two hemispheres, is larger in women than in men.

■ The MASSA INTERMEDIA, which connects the left and right sections of the thalamus, may be larger in women than in men.

■ The PLANUM TEMPORALE, the name for the uppermost level of the temporal lobe, is usually larger on the left hemisphere, where it overlaps the part of the brain involved in language. In some women, it may be larger on the right side.

So what does all this mean? It’s not clear. There is some evidence that the brains of men and women are organized slightly differently. Typically, the right hemisphere of men’s brains is involved in visual and spatial activities, while the left side is involved in language. But studies of people who have suffered brain damage have revealed that while that left-right split holds true for men, it does not seem to matter for women. This has led researchers to speculate that brain skills are distributed differently between the sexes. It is also uncertain what effect hormones exert on the brain. Most of the information we have about this comes from studies of people born with mutations in their sex chromosomes. These mutations include one responsible for a rare condition called idiopathic hypogonadotropic hypogonadism, in which boys do not produce testosterone when they reach puberty. Men with this condition do poorly on visual-spatial tests, suggesting that testosterone may help the part of the brain involved in spatial tasks to mature.

The bottom line is that boys and girls are born with brains that are equal in most ways. And with the right encouragement and challenges, they grow up with a full range of abilities, regardless of their sex.

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Structures that differ in male and female brains (images credit: Kathryn Born)

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Prenatal Development — The Dana Guide

By Ann McDonald
November 2007

Sections include: nature and nurture, building blocks of the brain, growing by leaps and bounds, the first glimpse and flutters, moving, thinking, being: the cerebral cortex, cells start to talk, preparing for birth

The first signs of pregnancy are subtle. A woman’s menstrual period does not arrive on time. Her breasts may feel sore to the touch, and she may need to urinate more often. Perhaps she feels more tired than usual. She may suffer from nausea when she smells certain foods, or might crave others. But all these signs can have other explanations besides pregnancy. To confirm their suspicions, many people buy a home pregnancy testing kit, available in any pharmacy. Such tests work as soon as the first missed period, but they are more reliable if you wait another two weeks. By that time, the developing fetus is about a month old. And the basic components of its brain have already formed.

Many people do not realize just how early a child’s brain begins to develop—and how long it continues to mature after birth. The process starts between the second and third week of fetal development, and it continues well into early adulthood. No other organ in the human body takes so long to develop as the brain does or goes through as many changes. This unique growth process explains the brain’s complexity and amazing activities, as well as its vulnerability to injury.

Nature and Nurture

You have probably heard the phrase nature versus nurture. It tends to pop up whenever we gain some new insight into human development. Has some aspect of personality or intelligence come about as a result of genes, part of our inborn nature? Or because of the influence of parents, teachers, or other aspects of the environment that nurtured us?

When it comes to the brain, the answer is really both. Some neuroscientists have compared the building of a human brain to the weaving of cloth: some threads are supplied by genes, others by the environment. In the resulting fabric, the different strands are so tightly woven that they are virtually indistinguishable. Other theoristshave compared the brain to a seedling, which is full of potential but needs the right mixture of nutrients, sun, and rain in order to growinto a tree. So the debate in brain development is not one of nature versus nurture, but of how these factors interact and which is more important in the development of particular traits, behaviors, and disorders. The consensus on these questions tends to change as we learn new information.

The brain is malleable because it develops partly as a result of the preprogrammed instructions encoded in genes, and partly as a result of exposure to the outside environment. Genes govern the type of brain cell produced, its location and function, and what type of neurotransmitters it will respond to. But whether a particular neuron will develop further and realize its full potential, or go unused and wither away, depends on external stimulation—everything from sight to sound to stress.

In the beginning your developing child follows a standard and predictable course of development. And what you or your mate continue to experience may feel like a straightforward, linear process: the baby becomes steadily larger in the womb, the ultrasound reveals more and more features, the mother feels more vigorous activity. But while a baby’s nine-month gestation includes many clearly defined stages, at the cellular level these processes tend to overlap. Some are repeated several times. This development is guided by the genes built into every cell of the embryo. It is by following those genes’ complex instructions that your child’s brain is able to develop from a group of primordial cells into one of the most powerful organs in the universe.

Building Blocks of the Brain

In the first month of pregnancy, the changes you notice in your body (or your mate’s) are subtle; the changes the developing embryo undergoes are enormous. At birth the child’s brain will consist of 100 billion neurons, organized into groups that perform such particular functions as interpreting sounds, storing memories, and learning new skills. Yet this complex organ, like every other part of the human body, must grow from a single fertilized egg. The brain develops at a phenomenal rate in the nine months from conception to delivery. At the height of this process, a quarter of a million new brain cells are born every minute.

In the first week, the fertilized egg goes through a series of divisions, giving birth to a hundred or so progenitor cells, all exactly alike. The cells are clustered in a small ball known as a blastocyst.

During the second week, the original generation of cells has given birth to others, which begin to differentiate, or take on unique characteristics that distinguish them from their cousins and forebears. As the cells differentiate, the developing embryo evolves from a small round cluster of cells into an elongated disk that consists of three layers of tissue. The upper layer of the disk, or ectoderm, will eventually give rise to the outer covering of a person (skin, fingernails, and hair) and—with help from the middle layer, or mesoderm—to the brain and central nervous system. The bottom layer, or endoderm, gives rise to internal organs, such as the lungs and stomach.

Brain development begins with a process known as induction, which takes place in the third week of embryonic growth. Cells multiply rapidly along the lines of the ectoderm so that a structure called the neural plate forms. This process is not completely understood, but it seems to be sparked by contact between the ectoderm and mesoderm. Chemical factors produced in the mesoderm create a reaction in the neighboring ectoderm, pushing some cells along the developmental pathway that leads to skin and hair, and others on a different developmental pathway that leads to brain and spinal cord.

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At about the third or fourth week after conception, the neural tube begins to form and to show bulges that will become parts of the brain and spinal cord. (image credit: Kathryn Born)

By the fourth week, part of the neural plate has folded in on itself to form a neural tube. At this point, primitive brain cells called neuroepithelial cells begin to divide rapidly, or proliferate. At first the wall of the neural tube is composed of only a single layer of such cells. Yet this initial layer grows, forming additional layers. Cells proliferate at a furious pace, in part because the neuroepithelial cells begin to divide into three new cells rather than two.

Three bulges emerge from the top of the neural tube, eventually giving rise to the forebrain, midbrain, and hindbrain. The rest of the neural plate becomes the neural crest, which will become the spinal cord. As cells proliferate in the three primitive brain structures, the brain begins to grow and fluid-filled spaces known as ventricles form in the middle. Even at this early stage, primitive brain cells are organized into distinct groupings known as neuromeres, visible as tiny grooves on the ventricles. Although the neuromeres disappear in another two weeks, they are precursors of the large-scale differences between parts of the brain that we can easily see.

Thus, as the embryo enters its second month of development (before the mother may even realize she is pregnant), the brain and the central nervous system have already begun to take shape. That’s one reason it is so important to take care of your health, even at this early stage.

Growing by Leaps and Bounds

By the second month of pregnancy, you may know that you are pregnant, or that your mate is. A mother may feel morning sickness, but aside from that the external signs of a pregnancy are still subtle. But probably you have begun to wonder what this child might be like when it is born. Will it be a boy or a girl? Will it have its mother’s eyes, or its father’s? Will this child grow up to be an athlete? Or an astronaut? A gifted musician?

While you daydream and speculate, your developing child is busy building a brain that will one day allow him or her to do the same. During this second month of fetal development, the brain grows by leaps and bounds. Construction begins on all its major components. What happens in this month will lay the foundation for your child’s ability to see, hear, speak, and one day imagine his or her own child.

During the second and third months of fetal development, the growing brain begins to take shape. The hindbrain gives rise to the medulla oblongata and the pons (part of the brain stem), which are involved in many functions essential to life, such as breathing and heartbeat. The cerebellum, the part of the brain involved in maintaining balance and coordinating movement, emerges partly from the hindbrain and partly from the midbrain.

But it is the forebrain that undergoes the most complicated changes. The forebrain divides into two distinct structures: the diencephalon and telencephalon. The diencephalon develops into the thalamus and hypothalamus, which will affect everything from emotions to sensory perception. The telencephalon gives rise to several parts. First come the hippocampus, which eventually will be involved in short-term memory, and other structuresinvolved in the olfactory pathways, which will enable your child to smell. Next, the telencephalon produces the basal ganglia, which will eventually contain structures that control movement, sensory information, and some types of learning. The amygdala will eventually help the brain attach emotional significance to signals it relays elsewhere.

The last structure to evolve out of the telencephalon is the cerebral cortex, one of the most complex parts of the brain and the site of what are considered “higher functions”: learning, language, and abstract thought. The cerebral cortex begins to develop in the eighth week of embryonic growth but will continue to form during much of the prenatal period. The connections between neurons in the cerebral cortex continue to mature into early adulthood, and some experts say they never stop maturing.

This tremendous growth is possible because the neurons are still proliferating. Although cells have been dividing since the moment of conception, this activity builds to a fevered pace about day 40 (or in the sixth week) of embryonic development. This process, known as neurogenesis, continues until day 125 (around the seventeenth week). Even then, it does not completely stop but only slows down.

In these early months of prenatal development, cells not only proliferate—they begin to take on particular identities. This process starts when some of the cells in the ventricular zone stop dividing and begin to do a microscopic dance. Precursor cells divide on the innermost surface of the neural tube, which borders the ventricles, then move to the outermost surface to synthesize DNA, the blueprint of life. Then the precursor cells return to the ventricular surface to divide again. The cells repeat these steps a set number of times, depending on their types.

With all this back and forth, patterns of similar cells develop into columns, or what the neuroscientist Pasko Rakic has suggested is a protomap for the fully developed brain. According to this model, columns of cells form on the surface of the ventricles with genetic instructions on how many particular cells the brain needs, where they will eventually be located, and what they will do. The result is both a prototype of the brain and a map of it—hence the term protomap. Some neuroscientists have challenged this theory as too simplistic, but it offers a helpful way to picture how the parts of the brain develop.

The primordial cells in the neural tube eventually become either neurons or long, thin glial cells. The neurons are the brain cells that do the actual work of thinking and controlling movement. The glial cells have been compared to scaffolding that helps guide the building of the brain, especially the cerebellum. These glial cells sprout from the ventricular zone, extending upward to the outer surface of the developing brain. Neurons begin to migrate in different directions, depending on their preprogrammed roles.

Guiding all this movement are genes, which we can compare to blueprints. Each contains instructions for creating a protein, which in turn might induce cells to divide or perform particular functions. Early embryonic cells divide and give rise to progenitor cells, which then give birth over several generations of divisions to more specialized cells. No one gene contains a master plan. Rather, one set of genes controls the initial phase of development, other genes then kick in and take it to the next level, and so on.

The First Glimpse and Flutters

During the first months of pregnancy, you probably do not notice much external change. If you are the mother, perhaps your waist has begun to thicken a bit as your uterus grows. You may have trouble wearing some tighter-fitting clothing but are probably not yet in maternity clothes. As the middle period of pregnancy arrives, however, you are likely to become more aware of the life growing within.

Your earliest glimpse may come from an ultrasound, often performed for the first time in the third month of pregnancy. (A second ultrasound may be performed later in pregnancy as well.) Though its image is blurry, the fetus is starting to look human. An expert can usually point out the large head, fingers and toes, even tiny eyes and ears. As the ultrasound technician prods your abdomen with the probe, the fetus might dart away. Its movements are jerky and uncoordinated, and you probably will not be able to feel them. At the end of the third month, the fetus is still very small—about 3.5 inches (9 cm) from head to rump, and weighing only 1.7 ounces (48 g).

An expectant mother’s experience changes at the end of the fourth month, or more likely the beginning of the fifth. Many women then feel the first slight movement, or a fluttering in the abdomen. Known as quickening, this is the first physical sign a mother has that the fetus has begun to move. This is often the most exciting time for parents, the point at which they start to become acquainted with their child and anticipate its birth. The fetal movements, which will grow to somersaults, jabs, kicks, and the like in the sixth and seventh months, can seem deliberate. And in a way, they are. Your child is helping to develop its own brain, with each turn and move accelerating processes that have been under way for some time.

Moving, Thinking, Being: The Cerebral Cortex

The middle part of pregnancy is a significant time in fetal development, when the brain evolves from a primitive structure into a much more complex form. Cells continue to proliferate and differentiate during this phase, but they do much more besides. They have begun to travel (migration), form communities (aggregation), and make connections that facilitate the communication necessary to brain function (synaptic formation). All of this lays the foundation for what makes us human: movement, learning, conscious thought, and memory.

Although all of brain development involves some combination of cell growth, migration, aggregation, and synaptic formation, this process is most dramatic in the cerebral cortex. This is the largest part of the human brain and the site of the so-called higher functions. The cerebral cortex builds itself from the inside out, with the neurons of the deeper layers being made before those of the outer layers. But all the neurons are born deep inside the brain, in the ventricles, so some must travel to the outermost reaches of the organ. At about the eighth week of embryonic development, primitive brain cells begin to migrate outward from the innermost part of the brain and start to build the first layer of the cerebral cortex. Succeeding groups of cells follow, slowly building all six layers of the cortex, a process that continues for most of gestation.

Meanwhile, neurons continue to proliferate, creating new cells. The peak growth occurs in the fourth and fifth months of pregnancy, when the cortex (also known as the brain’s gray matter) grows much more rapidly than the supporting structures underneath (known as white matter). By the time the cortical growth spurt ends, in the sixth or seventh month of development, 70 percent of the brain’s neurons are located in the cerebral cortex. At the same time, the fetal skull has begun to harden as cartilage turns to bone throughout the body. Both the rapid growth and the hardening skull help explain why the cortex acquires its characteristic folds, but that wrinkling is far from random. The fully developed cortex has peaks and valleys that are generally the same from one person to the next, pointing to some underlying genetic blueprint. Even so, there are many small differences between individual brains, even the brains of identical twins, who share the same genes. The exact contours of the cortex are thus a product of both nature and nurture.

Dana Guide - Chapter 5, Page 73 - Spotlight

Neuron climbing a glial cell: During development, neurons follow specific cues and migrate along glial cells (the support cells that act as the “road” on which the neurons travel) to their designated locations in the brain, spinal cord, and nervous system. Scientists say this journey, for some neurons, is like walking from New York to California. (image credit: Kathryn Born)

As cells migrate, they travel along particular pathways to reach their preprogrammed destination. Exactly how the cells know where to go is not entirely clear. Rakic’s theory suggests that the protomap contains instructions that point the cells in the right direction and then, as the cells head out, other signals guide them along the way. Most cells use other neurons’ offshoots, known as axons, and chemical signals to guide their journey. Others climb along glial cells, which are so elongated they resemble strings or small plants; when these glia are no longer needed, they either degenerate or become permanent supporting cells in the white matter of the brain.

Sometimes, in spite of all the signals and directions, migrating cells lose their way through the layers of other cells. About 3 percent arrive at the wrong place. If too many neurons lose their way, part of the cerebral cortex may never develop. Some neuroscientists believe that errors in cortical cell migration contribute to certain types of mental retardation, epilepsy, developmental delays, and perhaps even schizophrenia. In extreme cases, the cortex will be smooth rather than wrinkled, a condition known as lissencephaly. A dramatic example of problems with cell migration appeared in the aftermath of the nuclear blasts over Hiroshima and Nagasaki. Many people who were exposed to the radiation between the tenth and seventeenth weeks of their fetal development grew up with impaired higher brain functions; they could not hold jobs and were institutionalized. Autopsies revealed not only that these victims’ cerebral cortices were thinner than normal (indicating that not all cells had migrated successfully), but also that errant cortical neurons were scattered throughout the supporting white matter.

Cells Settle In and Start to Talk

Much as people do when they move to a new place, cells that have recently arrived at their proper destination seek out similar cells and begin to form their own versions of communities. The technical term for this is aggregation. The cells recognize each other by their distinct biochemical properties and receptors. Cell adhesion molecules, sometimes called sticky molecules, help the cells bind.

Once settled, a neuron sprouts an axon for sending signals to other brain cells, and numerous dendrites for receiving signals from others. In forming connections, neurons do not simply reach out randomly to the closest cells. They seem to be programmed to seek out specific targets. In some parts of the brain, such as the cerebral cortex, the cells even align themselves in the same way, axons pointing down and dendrites pointing up.

The axons that send signals and the dendrites that receive them communicate for this purpose at specialized contact zones, where the sending axon physically connects to the dendrite. These specialized contact zones are called synapses; they were named from the Greek word that means “to grasp.” Although there is a thin gap between the axon and the dendrite at such connections, the chemical signals (neurotransmitters) from the axon can diffuse rapidly across it to deliver the signal to the dendrite. As the signal spreads from the cell body of the sending neuron, a wave of activity flows down the axon, caused by the movement of sodium ions from outside the cell into the axon. As the wave of activity reaches the nerve terminal at the synaptic contact point, calcium ions also enter the axon and trigger the release of the neurotransmitter. The neurotransmitters bond with receptors on the target cell, prompting a new electrical signal to surge through that neuron. In this fashion, brain cells can send many different messages to each other with varying degrees of urgency.

Although most neurons connect to a limited number of other brain cells, some send signals to as many as 10,000. This web of communication helps explain the brain’s vast computing power. Scientists are still trying to explain how so many connections are made, and so precisely, in the developing brain. In some cases, the distance an axon travels before reaching its target is astounding, as much as a thousand times the diameter of the cell itself. At other times, axons must twist and turn along their route. Some grow as long as a few inches. Although more remains to be discovered, several mechanisms have been identified that help explain how synapses form.

For starters, time determines, to a great degree, when a neuron will first sprout an axon and begin making connections. We believe that neurons form the bulk of their connections during a particular period in their development, soon after they arrive at their destinations and sprout axons. At that time, they can make connections only with cells already in place. If other cells arrive later, the neuron will no longer be able to forge a link. Neurons that arrive early seem to connect to their neighbors. Later, when the communities grow in number, cells need additional help to find the right targets for their connections.

Although the sprouting of an axon is directed by every cell’s genetic instructions, the path of further growth is aided by various chemicals and molecules in the surrounding tissue. The tip of the axon, known as the growth cone, sprouts tiny filaments (filopodia) that continuously extend and retract, almost as if they are testing the environment and feeling their way ahead. Meanwhile, target cells produce various chemicals, called chemotrophic factors, that both encourage an axon to grow and attract it in the desired direction. (Cells that are not appropriate targets produce chemicals that repel the axon.) These factors spread through the tissue, and axons with receptors that can bind with them grow in that direction. Meanwhile, filopodia that do not encounter the appropriate chemicals retract, so that the growth does not go off in the wrong direction.

In this way, the axons find their targets by taking the cell equivalent of baby steps, rather than one long leap into the unknown. They grow toward higher concentrations of chemicals that they find attractive, avoiding cells that produce chemicals that are repugnant. Chemotrophic factors are usually present in small, well-defined areas. When the journey is long, still other molecules function almost as beacons, or what the neuroscientist Per Brodal has called signposts, along the way, helping guide growing axons on their journey so that they reach their proper targets. Other axons come up behind, following their lead.

Like-minded axons, which share the same sorts of targets, also ease the process by squeezing out sticky substances called neuronal cell adhesion molecules, or N-CAMs. These N-CAMs help keep individual axons from getting lost. Such axons may actually huddle together, forming collective groups known as fascicles. Like any clique, these groupings are exclusive; axons that do not express the same N-CAM, or express none at all, are discouraged from coming near.

External stimuli also help cells in the developing brain make connections and strengthen them. When the fetus kicks or sucks its thumb, the neurons that control movement are exercised and form more connections between more axons and dendrites. Typically, for instance, a fetus begins moving its arms and legs around the tenth week of development. At first these movements are uncoordinated and random. But gradually the fetus becomes more purposeful in its movements (as any pregnant woman knows). The child’s increasing ability to coordinate movements, which continues to grow after birth, is due to the gradual development and strengthening of the appropriate transmitters, receptors, and connections between all the cells involved. Practice helps make perfect.

Preparing for Birth

During the last stage of pregnancy, parents and fetus both are preparing for birth. You may take childbirth classes, decorate the nursery, and be guests of honor at a shower. The developing fetus, meanwhile, has grown so large that it has difficulty moving within the uterus. Its brain is maturing rapidly. By month seven, electroencephalography (EEG) can detect fetal brain waves. The fetus can see and hear, although these senses are only in the earliest stages of development and will become much more refined outside the womb. During this last phase of development, the earlier processes of cell proliferation and migration continue to some degree, and synapses continue to form all over the brain. But two new processes begin in earnest: a pruning of unnecessary cells and connections, known as apoptosis, or programmed cell death, and the protection, known as myelination, of vulnerable neurons and connections.

Until this point, everything about brain growth has been about more: more cells, more axons and dendrites, more synaptic connections. And the result is more than the brain needs. The brain overproduces cells and synapses. Apoptosis provides balance. This large-scale elimination of neurons affects some parts of the brain more than others. Relatively few neurons in the spinal column die, as compared with five in ten motor neurons (which control muscle movement), and nine in ten cells in the cerebral cortex.

How all this happens is still a matter of investigation and conjecture. We know that when a cell undergoes apoptosis, its DNA begins to fragment and it eventually dies. What is not as clear is what triggers apoptosis. One theory is that cells need growth factors in order to survive, much as people need nutritious meals on a regular basis. Once a neuron makes the right connections with other brain cells, it receives the growth factors it needs. Cells unable to make appropriate connections “starve” and die. Another theory is that neurons are preprogrammed to self-destruct but that exposure to growth factor inactivates the genes that contain these instructions.

In the final months of pregnancy, the brain also begins to protect itself. Around the eighth month of prenatal development, myelination begins; it will continue well into childhood. Myelin is a protective membrane produced by oligodendrocytes, which are types of glial cells. The membrane extends from the oligodendrocyte’s body and wraps itself many times around an adjacent axon, forming layers. Myelin has sometimes been compared to the rubber that coats electrical wires, but it is actually even more useful. Myelin not only protects the brain cells; it helps them communicate by facilitating, and speeding, the transmission of their signals. Since electrical signals can enter and exit the axon only where it is exposed, the myelin covering ensures that those signals will pass quickly to the target brain cell. In multiple sclerosis, Guillain-Barré syndrome, and other conditions, the myelin covering is damaged; the axon is thus exposed to signals from neurons it normally does not communicate with, and the result is something like an electrical short circuit, causing loss of motor control and other problems.

Myelination occurs at different times in different parts of the brain. Generally, motor and sensory brain cells are protected first, before birth. The last area to be myelinated is the cerebral cortex, and that happens long after birth, in childhood. The process of myelination coincides with the development of more advanced and coordinated skills. Your child will become better able to control arm and leg movements, and will thus be better able to crawl and walk. Over the same period your child’s cerebral cortex becomes myelinated, he or she will start to form words, string them into sentences, and finally form abstract thoughts, one of the highest brain functions of all.

Breathing Lessons—and Bedtime Stories

By the eighth and ninth months of pregnancy, you are probably practicing your breathing in preparation for the birth. (You may be eager to get this over with at last!) As the baby’s due date approaches, many parents wonder if they should begin to talk to the developing fetus, or even begin to teach it in some way, such as exposing it to music. Certainly some intriguing research shows babies pick up on prenatal experiences. Newborns suck harder when they hear their own mothers’ voices than when they hear another woman’s, for instance. In one set of experiments, researchers asked women to read a Dr. Seuss book aloud twice a day in their eighth and ninth months of pregnancy. Subsequently, the newborn babies sucked more energetically when their mothers read that book to them than when they read another.

Other researchers have gone so far as to assert that a program of stimulation before birth can produce a brighter, more active baby afterward. But most neurologists are not so sure. They worry that well-intended parents may overstimulate their offspring in the womb. A large part of the meaning that babies pick up from their parents’ talk and play is emotional, based on the tone of the interactions; if parents are stimulating babies in an anxious way, or doing so without happiness because they feel obliged to, the effect may be counterproductive. The consensus advice is fairly straightforward:

■ Remember that the major developments your fetus undergoes in the womb are physical rather than mental. The best advice for mothers is to eat well and avoid such toxic substances as alcohol and drugs.

■ As long as you do it in moderation, talking with your fetus and exposing it to music and stories can’t hurt. This is best done in the eighth and ninth months, when your fetus has developed the brain capacity to hear and perhaps even remember sounds.

■ A fetus needs periods of rest, just as we all do. As active as the fetus may seem at times, it also needs to drowse quietly. Overstimulation can disrupt these rhythms and may even be stressful.

■ Be wary of any “fetal development” program that is sold commercially, especially if it carries a hefty price tag. When the marketing pitch comes across more clearly than the medical research, it is wise to be skeptical. When in doubt, check with your obstetrician or pediatrician.

If nothing else, remember that your child’s brain continues to develop well into young adulthood. You will have plenty of time to interact with, and challenge, your child after he or she is born. And then you will also have the satisfaction of seeing your child react, learn, and grow.

Myelin—the white fatty insulation around axons—helps move the electrical impulses more efficiently. Myelin sheaths are formed by a type of glial (supporting) cell known as an oligodendrocyte. As the brain and nervous system develop in the embryo, the oligodendrocyte wraps around and around the axon in layers resembling an onion. Lengths of oligodendrocytes wrap around the entire length of the axon in a pattern much like links of sausage. (image credit: Kathryn Born)

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The Dana Guide to Brain Health