2.5
INTERLUDE
A brief biography of the brain
All of us started out life as a single cell, a fertilized egg that then divided into two cells. Those two divided into four, and so on, exponentially. Early in this cell-division stage of life, cells begin to differentiate and specialize, eventually to become skin, toes, veins, tendons, pancreas cells, brain cells—all the different parts and components of your body. At around four weeks of gestation, you can see the brain emerging in ultrasound images. What is this young developing brain thinking about? Or is it devoid of thought, waiting for birth to begin its mental life?
The Greek physicians Herophilus and Erasistratus discovered the nervous system in 322 BC, placing the seat of thought in the brain. It might be fair to say that they were the first neuroscientists. Previously, Aristotle and others thought the brain’s function was simply to cool the blood, due to its many folds and creases. It’s been said that the Bible taught us the centrality of ethics and that the ancient Greeks taught us the centrality of knowledge and rationality. Just FYI, the Bible did speak of the brain, in Job 12:3 (Iyov, responding to Tzofar, “But I too have a brain, as much as you”), and in Jeremiah 5:21 (“Hear this, stupid, brainless people, who have eyes but do not see, who have ears but do not hear”). These passages were written three hundred years or so before Herophilus and Erasistratus took to studying the brain. How the authors of the Old Testament knew this centuries before the Greeks is a topic for theologians, literary historians, and philosophers of science, not a simple country neuroscientist like me.
During week four of gestation, you can recognize the brain’s four distinct structures. One of them, the optical vesicle, will grow into the key components of the visual system: the optic nerve, retina, and iris. Within another week, the brain stem and cerebellum start to differentiate—including the neural circuits that will eventually guide movement, sleep-wake cycles, and temperature regulation. Neural growth in the womb will reach a rate of 250,000 neurons per minute. From their humble origins in a single cell, all the different specialized systems find their places in the brain and in the body. These early, undifferentiated cells are called stem cells because they are like the stem of a flower—which will eventually create petals and leaves and pistils and stamens—all the different parts of the flower. Because stem cells have the power to become anything, they are on the frontier of efforts to repair aging and damaged tissue and to cure diseases. In the early days of stem cell research, the only way to get them was to take them from discarded human embryos. This led to an ethical debate during George W. Bush’s presidency. The debate became moot in 2017, when scientists discovered a way to create stem cells from adult human skin cells. Stem cells are promising for a range of medical treatments. In the next twenty years, we may well see stem cell therapies taking the place of contact lenses and hearing aids, skin moisturizers and hormone replacement therapies, and treating diabetes and cancer. They may even reverse decaying memory traces.
As the fetus’s cells divide and differentiate, the brain gets built in bits and pieces. Among the first pieces to arrive is our visual system, followed quickly by our other senses. By week twenty the auditory system is fully functional. The developing fetus can hear the world, filtered by amniotic fluid, uterine walls, and muscle; it sounds like what you’d hear if you put your head underwater in the bathtub or a pool. The fetus can detect variations in loudness, pitch, and the rhythms and durations of sounds. From this information, the developing brain begins to wire itself up, to form neuronal connections that map out the very nature and structure of the auditory world in preparation for life outside the womb. The bass lines and chord progressions of music are extracted alongside the pitch and rhythmic patterns of speech. One year after birth, the infant will show a preference for, and familiarity with, the specific kinds of sound patterns it encountered in the womb.
At week twenty-eight, the eyes open and even start to blink. The nose started to develop at week seven, and two tiny nostrils formed around week eleven, remaining plugged up until around week thirty. At that point, the soon-to-be baby starts to smell and become familiar with its mother’s scent—this is an important part of infant-parent bonding and prepares the infant for nursing, because the smells of the womb are chemically similar to those of the mother’s breast milk. In fact, new research suggests that even before the nostrils become unplugged, the baby becomes familiar with its mother’s scent as the amniotic fluid flows through its mouth and nasal cavity.
Why are humans at the top of the food chain? We’re not the fastest runners—even a cat is faster. We can’t lift the most weight. We don’t have fangs like a lion, poisonous venom like a rattlesnake, armor like a rhino. We learn in school that it’s the opposable thumbs and using tools. But it’s not—it’s the brain.
All our thoughts and experiences are mediated by our brains, and the building blocks of our brains are their specialized cells, neurons. There are 85 billion of them in an adult brain. The electrical machinery of your brain consumes vast amounts of fuel—around 20 percent of all the energy of the entire body, even though the brain represents only 2 percent of our body weight. It uses up about twenty watts of power, enough to power my car stereo at full bore in 1978.
A baby’s brain is a lot like a mass of undeveloped land, and the process of brain development is like bringing in tractors to cut roads through the tall grasses. The neuron is a specialized cell for transmitting information in the form of nerve impulses. Its long transmission line, the axon, is like a highway. Its branching dendrites are like a bustling city of feeder roads, frontage roads, streets, driveways, and alleys. There are constraints in both sides of the analogy. You can’t easily build a road in solid granite or through a mountain; not every neuron can synapse (connect to) every other neuron. The topographical constraints of the brain limit certain kinds of connections and promote others. For example, your plot of undeveloped land may have some existing trails where the deer have already trampled down the grasses and softened the dirt—that would be a path of least resistance for building a road. And there are some places where it is more advantageous to have a trail than others—to the water well, for example. The brain gets general instructions about the topography of its land from information coded in DNA, which we might say is the brain equivalent of trail maps that, among other things, show all the deer trails.
Our brains are predisposed to immense neural growth during the first year of life. An explosion of new connections occurs—more than 1 million per minute at birth, and by six months, up to 2 million new connections a minute. The neurons in the baby’s brain begin connecting to one another as they learn about the world; each of those connections represents an experience, a memory, or a perception. When the infant learns that early-morning sunlight is followed by a meal, or that crying will bring someone to come change a soiled diaper, an electrochemical reaction begins inside its brain. In the tiny space between two neurons a new connection is formed, called a synapse. Once neurons are synaptically connected, their electrical activity will become synchronized. As neuroscientists say, they will fire together. This neural firing in tandem is the essence of thought, learning, memory, and experience. Connections like this are forged throughout the brain, and any given neuron could have up to ten thousand of them. If you work out the math, you’ll find that by adulthood, there will be more connections in a human brain—more possible thoughts and brain states, that is—than there are particles in the known universe. This may be one of the reasons we can have so much trouble predicting one another’s behavior.
Starting around six months, the neural pathways that transmit electrical pulses become more efficient through a biologically ingenious evolutionary adaptation that insulates them. A layer of a fatty, nonconducting biological material called myelin (MY-el-linn) coats the transmission lines and increases the transmission speed. Myelin is white in color, and neuron cell bodies are gray. What we call white matter in the brain are the bundles of these highly efficient transmission lines connecting the gray matter computational hubs.
There are hundreds of different neuronal types. How does a single cell—the fertilized egg—give rise to each of them? Proteins determine how neurons acquire their identities, and the how and where of axons and dendrites growing toward target cells and forming synaptic connections. The protein genes in your DNA contain instructions about how and when to make these proteins. Humans have roughly twenty to twenty-five thousand protein-encoding genes on twenty-three pairs of chromosomes. (The number of non-protein-encoding genes is about twenty-six thousand. Some individuals are missing one chromosome from a pair, leading to monosomic conditions such as Turner syndrome; some individuals have a third chromosome, leading to trisomic conditions such as Down syndrome.)
The growth of the nervous system depends on the expression of particular genes at particular places and particular times during development. Most of the key instructions for the development and formation of the nervous system are found in organisms separated by millions of years of evolution. Humans have 99 percent of our DNA in common with chimps. And that banana that we and our chimp cousins like to eat? We have a whopping 60 percent of our DNA in common with it, as well as with the fruit flies that like to swarm around it. This is because many of the genes that are necessary for cellular housekeeping—basic cellular function, replicating DNA, controlling the life cycle of the cell, and helping cells divide—are shared across plants and animals.
These blueprints are ancient. The common ancestor that gave rise to both humans and chimps lived between 4 and 13 million years ago. And the overlap with bananas is because animals and plants evolved from a common ancestor some 3 or 4 billion years ago, named LUCA (for last universal common ancestor). Because of this similarity, neuroscientists have learned most of what we know from relatively simpler organisms that are easier to study, both logistically and ethically. If you really want to sound in the know, casually mention in a conversation C. elegans (a worm) and Drosophila melanogaster (the fruit fly)—two organisms that have taught us a great deal about how DNA works.
The Role of Exploration and Input
The job of the infant brain is first to explore the world, and then to create neural circuits that incorporate that understanding of the world. Some understandings appear to be hardwired, such as understanding (at two months) that objects fall down, not up. But whether this is actually innate or learned is still a matter of debate—by two months, babies have had a lot of experience with the world.
These two jobs of the brain—exploration and wiring up the results of that exploration—are robustly supplemented by a third major job that reaches a peak in old age: prediction. Our brains try to find patterns in both the physical world and the world of ideas, and to make predictions about them. This entails forming categories, making inferences, and problem solving—the operations of higher cognition.
Although the brain begins to take in information while still in the womb, it does so in a state that might best be described as semi-awake, or dreamlike. How does the nascent, developing brain get “turned on” to operate more like a postnatal brain? Neurobiologist Evan Balaban describes the fetal brain this way:
Most of us biologists would expect to see something that looked like adult brain function, maybe just not as much of it. We’d expect to see that start off slowly and grow. And what we see instead, almost until birth, is these multiple, different states that the brain is in, none of them that look like being awake.
Are these states like being asleep, or like being in a coma, or a different state entirely? Balaban, who is good with electronics, developed a small transmitter that can record brain-wave activity from embryos to answer this question. One thing we know already is that in fetal brains that are normally not getting much stimulation from the outside world, giving them external stimulation has an enormous effect on their development. And giving external stimulation to a newborn is essential for normal brain development; without it, there can be terrible consequences.
At birth, the receptors for the five senses (vision, hearing, touch, taste, and smell) are continuing the job they started in utero, branching their way to the appropriate part of the brain to deliver to your consciousness an impression of what is out there in the world. But they need perceptual stimulation to grow. At this point, everything is new to the baby—the feel of milk going down their throat, the sound of voices down the hall, the many colors of the environment around them.
During the first six months or so of life, the infant brain is unable to clearly distinguish the source of sensory inputs; vision, hearing, smell, touch, and taste meld into a unitary perceptual representation—as William James called it, a blooming, buzzing confusion. It’s like the Grateful Dead sang, “Trouble with you is the trouble with me / Got two good eyes but you still don’t see.” The regions of the brain that will eventually become the auditory cortex, the sensory cortex, and the visual cortex are experientially undifferentiated, and inputs from the various sensory receptors have the potential to connect to many different parts of the brain, awaiting the pruning that will occur later in life.
With all this sensory cross talk, the senses are merged, and the newborn experiences a jumbled flood of sensory impressions. The stream of information from the eyes mixes in with those from the ears, nose, mouth, and skin. The young infant lives in a state of psychedelic splendor in which a green light might have a taste, or their mother’s voice might elicit a warm and smooth sensation on the skin. Some babies never completely achieve sensory differentiation and then have a condition called synesthesia. There is some evidence that adults who develop certain forms of dementia can revert to this state, and it has been suggested that this may account, in part, for why some older adults develop a new interest in art quite suddenly.
It is only through interacting with the world that our infant selves learn to separate these sensory inputs; we learn that sounds have an internal mental quality distinct from tastes. Once we learn to differentiate the senses, we go through a phase of reintegrating the information from them. We learn that when someone’s lips are moving, sound usually comes out; that the sight of something falling to the ground is usually accompanied by a sound and maybe a vibration; that a pungent smell predicts a sharp taste.
While all this is going on, the infant brain overwires, making many more connections than it will need; axons and dendrites extend to more targets than are required for normal function in adulthood. The primary mission of the brain during the first few years of life is to make as many connections as possible based on sensory inputs, because the infant brain doesn’t know which ones it will need later on. New neural connections grow exuberantly. Think of it as building a new house—before the walls are put in you might add many more wires and cables than you’ll actually need because the cost of putting them in at this early stage is relatively low; you can always ignore the ones you don’t need. But the brain, being a biological organism, doesn’t simply ignore the ones it doesn’t need; it gets rid of them, by retracting them or using cellular housekeeping procedures to dismantle them.
Starting at around age two, the brain begins this two-decade-long pruning process, getting rid of synaptic connections that aren’t being used. By age ten, the brain will have pruned out 50 percent of the connections it had at age two, and this pruning continues into your twenties. Some adult, late-onset mental disorders, such as schizophrenia, may result from incomplete pruning of the prefrontal cortex during adolescence. You might ask, “Why don’t all neurons connect to every other neuron and just stay that way?” For one thing, the brain would be gigantic if it did this—twenty kilometers across. For another, pruning lets us sculpt an efficient brain in response to our particular environment. The pruning forces the brain to specialize, to create local circuits that can function apart from others and that can automate certain tasks. The end result is thousands of modules, each doing their own thing.
Take language, for example. The infant brain is configured so that it is receptive to learning any of the languages spoken in the world. We’re born with circuits that extract the form and structure of individual consonant and vowel sounds, grammar, syntax, and all the other features of language. A baby of Chinese parents is no more predisposed to learning Chinese than it is to learning Spanish—it is what that brain is exposed to that determines the language the child will speak. And there appears to be no limit to the number of languages a very young child can learn. Studies have disproven the old folk wisdom that a multilingual child is only a fraction as good at each of the languages it speaks—the different languages coexist in the brain and don’t take away from one another. In other words, it’s not like you’ve got a maximum capacity for a vocabulary of thirty thousand words that needs to be shared among the three or four languages you speak; each language gets its own vocabulary storage space in the brain, and no one has yet found a limit.
Guinness World Records lists Ziad Fazah as being able to speak fifty-nine languages. (He himself claims to be fluent in “only” fifteen at a time and requires a practice period to get up to speed on the others he knows.) The seventeenth-century poet John Milton could speak English, Latin, French, German, Greek, Hebrew, Italian, Spanish, Aramaic, and Syriac. One of the most impressive polyglots I know is the cognitive scientist Douglas Hofstadter, whose hobby is translating poems from one language to another while observing all of the formal and structural constraints of the poetic form. I once heard him take a five-hundred-year-old poem written in Old French and translate it into modern English, Shakespearean English, French, Italian, German, and Russian while trying to preserve the metric features of the original. He even did an English translation in which the first letter of each line spelled out the name of the poem and the poet.
How does pruning fit into all of this? The infant brain has the capacity to learn any of the thousand or so sounds of the world’s languages. As it hears a subset of those sounds in its environment, it wires itself up to them. No infant will hear all of these thousand sounds, and many of the sounds it hears it will not need—the passing foreign language speaker in the street, the mispronunciation because a talker’s mouth is full. We recognize speech sounds so quickly and effortlessly because there is little competition in our brains from the sounds of other languages that have been pruned out. Even multilinguals enjoy this efficiency because when they are immersed in conversation in a given language, their brain expects that language’s sounds to be heard, and so the neurons for that particular set of sounds are primed and on alert, and the neurons representing other sounds remain in the background.
Much of this pruning and synaptic connecting is based on our brains’ ability to take in a large amount of data and extract order and structure from it. Think of the world as having statistical structure that shapes the brain from repeated interactions. In that sense, the brain is a giant statistical analysis engine.
We learn based on co-occurrences of things. Babies learn that the /st/ sound at the beginning of the English words start or stop is a common cluster for starting words in English, but not in Spanish. (This is why Spanish speakers speaking English put a vowel in front of the word start, saying estart). Babies learn that the combination of /wszczn/ never appears in English (although it does in Polish). Statistical inferencing is the basis for other types of knowledge too. We learn that touching a hot burner, statistically, leads to pain. That statistically, crying tends to bring Mommy to the infant.
The more experience you have with something, the better your database of what is normal, and the more fine-tuned your mental representations become. A baby who has heard thirty instances of the vowel ă is not going to be as effective at recognizing it as a teenager who has heard thirty thousand instances of it. This statistical inferencing applies not just to language but to nearly everything we learn. It’s how we learn to read, by recognizing letters of the alphabet even when they appear in different fonts, and fonts you’ve never seen before. Your brain knows what an average letter a looks like and pulls variations of that form in, like a magnet, toward the average. This is a general principal of perceptual learning. Squares, circles, the color red, dogs, houses, tables, cups, hamburgers . . . our brains form categories for these based on the myriad examples of them that we see. We get to the point where we can see a distorted or geometrically impossible triangle that may not look like any one we’ve ever seen before, and we still see it as a triangle.
Interacting with the environment through movement and exploration is also important for proper neural growth and development. In infancy, it is the way that we learn to reach and grab, develop depth perception and those important visual-motor circuits. Successfully making contact with a moving target, such as a spinning mobile over the crib, or catching a ball, is so important that it has a special name, interceptive timing. This skill is a precursor to mathematical ability: It usually has to develop before a child can represent abstract concepts such as numbers.
Interceptive timing requires that we hone and develop prediction circuits in the brain—we have to predict where a moving object is going to be in the future, based on where it is now, its velocity, and its trajectory. You have to make a similar set of calculations about the movement of your hand in order to calibrate your grasp. Intrinsic in all of this is a sense of quantity and order. It may even be the case that interceptive timing is a prerequisite to language, because successful language use requires temporal order discrimination—in order to understand spoken or written language, sounds that appear quite close together in time have to be put in the proper order. The word tsar does not mean the same thing as star and it’s only because we have refined millisecond timing about whether the /t/ came before or after the /s/ that we can make sense of things.
Interceptive timing is a form of neuroplasticity—the brain accommodating information about the environment into its very wiring, changing itself to develop eye-hand coordination based on experience.
Critical Periods, Infant and Adult Neuroplasticity
The development of mental abilities is an intricate four-way dance of genetic instructions carried by DNA, the topography of the brain, environmental stimulation, and the culture we are raised in. Cortical development is dependent on experience. At birth, the perceptual system is waiting for information to come in that it can assimilate and wire itself up to. Depriving babies of the normal environment, both social and physical, during early critical periods of development can have profound effects much later in life. The term critical period is used to describe a time window within which a particular skill or ability needs to be cultivated with the right environmental input, or it can never be acquired. The time course of these windows is a statistical distribution, meaning that after a certain age it becomes extremely unlikely that an ability can be developed at all. Neural development during critical periods involves a multitude of processes in combination, making it difficult to reopen the windows once they’ve been closed.
You may remember some of these famous examples if you ever took a psychology class. Kittens who are deprived of normal visual input during a critical period never develop normal eyesight. Kittens that wore an eye patch, depriving them of input from one eye, never develop binocular vision or depth perception even after the eye patch is removed. Kittens raised in the dark never learn to see, even though their eyes are fine. (Many scientists today regret that the kitten experiments were considered ethical at the time, in the 1950s.) Although no one has done these experiments with humans, human children who are born without sight in one eye and have it restored after the critical period (by removing a cataract, for example) never develop depth perception either. The key fact here is that signals from the eye tell the visual brain when to grow and how to organize itself. It works this way for the other senses as well.
Similar to vision, the auditory system requires input from the environment in order to develop normally. Infants with peripheral hearing loss (a problem with the ear and not the auditory parts of the brain) are also subject to a critical period. Cochlear implants, which can provide needed input to the cortex, need to be introduced early in life in order to be fully effective. Implantation in the teen years or later never results in normal speech perception, although it does have the survival advantage of allowing the recipient to hear approaching objects that are not visible, such as a car coming up behind them.
The developing brain starts out with some biological biases—for example, that auditory output from the ear will wire up to the auditory cortex. But if experience doesn’t yield that, say, because of peripheral ear damage, different things will happen. The brain is thus like a block of clay in its early years and can be molded to its environment, almost any environment, within limits.
For decades we thought that auditory input was necessary for children to acquire any kind of language. Based on a new study just published in 2018, we now know that it’s not sound that the brain needs to acquire the statistical underpinnings of language; it’s language—even sign language. If deafness is identified early enough and the young child is exposed to sign language during the critical period for language development, the brain doesn’t miss a beat—it acquires sign language as a full-fledged native language just like it would acquire Dutch or Japanese or Swahili. This finding explains why deaf children who receive cochlear implants after ages eighteen to twenty-four months often don’t develop as well as deaf children who are exposed to sign language during their first year of life.
Language acquisition and sensory learning in general are possible because of neuroplasticity, the ability of the brain to change itself. It’s called neuroplasticity because the neuronal connections are shapeable and flexible, like soft plastic. And the brain is at its most plastic during the first few years of life. Fortunately, some form of neuroplasticity is with us throughout our life spans, even in our older years.
The term sensitive period refers to neuroplastic learning that can take place outside a critical period but which tends to be qualitatively different because it is less constrained by biological events. Two examples are playing a musical instrument and speaking a foreign language. These can be learned at any age, but those who take up either late in life may end up less fluent than those who do so early, say, before the ages of eight to twelve.
Although it’s not usually called a critical period, the time in the womb is certainly critical. Because the fetus is living within its mother’s body and sharing a blood supply and nutrients, things can go terribly wrong if the mother ingests anything that interferes with normal neural development. Steroids, hormones, alcohol, heroin, opiates, and other prescription drugs can all cause developmental defects. A famous case in my era was the prescription drug thalidomide, prescribed for morning sickness in pregnant women starting in 1957. More than ten thousand babies of mothers taking the drug were born with malformed arms and legs—twisted hands, an arm that stopped at the elbow, no thumbs. Taking the antidepressants Paxil and Prozac during pregnancy in rare cases has led to heart and lung defects. The use of Valium or other antianxiety drugs during the first trimester has been associated with facial clefts and malformations. And it’s not just mothers’ behaviors that contribute to fetal development—having an alcoholic father may increase the risk of having poorly developed organs, lowered ability to deal with anxiety, and motor deficits. A current threat to fetal health is the Zika virus, which causes microencephalopathy, a smaller than normal brain. There are a lot of syndromes with complicated-sounding names, but they all boil down to one thing: interference in the fetus’s environment.
Infants who are deprived of physical or emotional contact with their parents or caregivers experience a range of socialization problems that can last the rest of their lives. Infants don’t just need food and sleep; they need warmth and they need to be held, and as they develop into toddlers and children, they need adults to interact with them. This applies across species, not just to mammals, and across the life span. A child’s social development is a fragile system and good parenting is not a given, particularly among people who themselves may not have had good parenting. Parents who are inconsistent in their affections and attentions can also cause psychological harm. Many children who lacked healthy parental interactions grow into adults who cannot trust other people.
Neuroplasticity and Remapping
The brain has specific regions and circuits devoted to particular mental activities—we refer to the auditory cortex, for example, or the visual cortex or the motor cortex; we refer to the language areas of the brain. When brain development proceeds in a typical fashion, neurons from the eye find their way to the visual cortex. Similarly the sensory receptors in the fetus’s developing tongue wind their way through the brain to end up in the gustatory (taste) cortex so that a particular combination of impulses gets interpreted as “sour” or “sweet.” Neurons from the inner ear grow until they find the auditory cortex, stopping first at five relay stations that help to prepare the sound for detailed processing. (For those of you keeping track, the relay stations are the cochlear nuclei in the brain stem, the superior olivary complex, the inferior colliculus, the superior colliculus—for control of head turning toward startling sounds—and the medial geniculate body.)
But what about people who are born deaf, who don’t get any inputs from their ears to the brain? When this happens, the brain often adapts, rewiring itself to maximize its efficiency. Visual information, particularly that which conveys communicative information like sign language does, routes its way into the so-called auditory cortex, using that plot of neural real estate for communication. Sign languages have syntax and grammar just like spoken language—they are not composed of a bunch of unstructured gestures—and they use many of the same brain regions that spoken languages do. Consistent with the principle of critical periods outlined a moment ago, infants born deaf have to be exposed to sign language or receive cochlear implants during the critical period for language development or they will never achieve language fluency.
Similarly, blind people who read braille are using regions of their so-called visual cortex to do so, remapping their fingers’ touch information into areas of the brain that are normally activated by visual input. Neuroplasticity provides this compensatory mechanism for people who are blind from birth, and the altered cerebral organization allows their visual cortex to be activated by braille—tactile reading—as well as by speech.
How this remapping occurs is still unclear. We don’t know exactly how “auditory” neurons find the visual cortex, or how “visual” neurons find the auditory cortex. What would happen if the taste receptors from the tongue ended up in the visual cortex instead of the gustatory cortex? Would you see tastes? Would a sour flavor fill your eyes with a particular color or shape? This may be what is going on in infants during their stage of nondifferentiation, the psychedelic splendor.
In an extraordinary series of experiments, researchers have begun to understand a little about this. A team led by Mriganka Sur of MIT blocked the path from the retina to the visual cortex in young ferrets. With their usual pathway blocked, where did those retinal neurons connect? They not only found their way to the auditory cortex, but once they got there, they created a kind of topographical map of the ferret’s visual world inside of the auditory cortex. In humans, the existence of this sort of cross-modal plasticity may underlie the instances in which some people who are blind or deaf often have superior abilities in their intact senses.
Specific Effects of Aging on the Brain
Infancy is a time of perceptual and mental growth, but before that growth is complete we might say it is also a time of some confusion and lack of control over our bodies. In some respects, then, aging is similar to infancy. We may become incontinent. We may become unable to feed ourselves. We have trouble understanding speech and can’t always express ourselves as fluently and seamlessly as we’d like. Although sensory integration can begin to fail as we age, in general, older adults are more apt to use both auditory and visual information when presented together—which can be a good thing. They may need more time than younger adults do to successfully imprint new information.
Most of us will face a range of mental challenges as we age, and they come from multiple sources. Due to plaque buildup and partially blocked arteries (arteriosclerosis), blood flow may not be as smooth as it used to be. A reduction in the ability to produce neurochemicals may cause neurons to fire less efficiently. Dopamine levels fall about 10 percent per decade, and serotonin- and brain-derived neurotrophic factor levels also fall off with increasing age. Years of alcohol consumption can lead to neuronal death and are implicated in brain shrinkage. A decrease in the efficiency of synaptic connections leads to a general slowing of mental processes. There is decay or failure to regenerate the insulating myelin sheath surrounding axons—causing reduced electrical conductivity. Finally, most adults experience a gradual reduction in brain volume after the age of thirty-five of about 5 percent per decade through age sixty, with the decline speeding up after age seventy. All of these factors lead to a general slowing of cognitive function.
Much of this volume and weight reduction comes from shrinkage of the prefrontal cortex and hippocampus. The prefrontal cortex is what we use to set goals, make plans, divide a large project up into smaller pieces, exercise impulse control, and decide what we’re going to pay attention to. As I mentioned earlier, the prefrontal cortex is the last region to develop in childhood and doesn’t fully mature until well after puberty—into the late twenties. Because of its involvement in impulse control, there have been several cases in which defense attorneys argued that eighteen- to twenty-year-olds shouldn’t be held responsible for law-breaking acts because they lack an adult-like, mature prefrontal cortex that would allow them to exercise adult-like impulse control.
The prefrontal cortex is also the first cortical region to show wear and tear as we get older. “That is why one of the most significant problems in older adults is the ability to keep track of thoughts and prevent stray ones from interfering,” says Art Shimamura. “Brain fitness as we age depends significantly on maintaining a healthy and active prefrontal cortex. The more we engage this brain region during daily activities, the better we will be able to control our thoughts and think flexibly.”
Another important brain region that we need for mental engagement is the medial temporal lobe, above and behind your ears. This brain region includes that seahorse-shaped region called the hippocampus that is crucial for memory storage and retrieval. Imagine you’re out with friends seeing a play. It’s your prefrontal cortex that makes you want to read the program notes, that helps you to attend to what your companions are saying and to think up coherent things to say in return. Once the play starts, it’s your prefrontal cortex that restrains your impulse to talk or shout during the performance. In the meantime, the medial temporal lobe is linking up features of this experience with previous, similar experiences—the previous times you were at a play, the previous times you were in this theater, the previous times you were with these particular friends—and in addition, the medial temporal lobe is helping to store all these thoughts and experiences so that your brain will be able to retrieve them in the future. Without the medial temporal lobe, these links would all be lost and you wouldn’t be able to recollect the experience later as an encapsulated event. And without hippocampal function, you wouldn’t remember all the fun you had when you woke up the next morning.
Another big factor in mental decline has to do with myelin, that fatty coating around axons that serves as an insulator. White-matter tracts—the transmission lines of the brain, the myelin-coated axons—decay with age starting at age fifty or so, and remyelination slows down to the point where it can no longer keep up. While the gray matter of the human frontal lobe and hippocampus shrinks an average of about 14 percent between the ages of thirty and eighty, shrinkage of white matter is even more drastic, averaging 24 percent. Moreover, unlike gray matter, which shows a more gradual shrinkage over time, the decline in white matter is particularly steep between the ages of seventy and eighty. It’s not that the tracts themselves disappear; it’s that the loss of insulation causes misfirings and disturbances of the electrical signal and slows down the transmission of thoughts in the brain.
This leads to a generalized slowing in older adults, affecting all of our mental systems, including the transmission of perceptual information, memory, decision making, and motor movements. That in turn may account for memory problems and other cognitive slowing because the white-matter tracts that are most compromised are those in the prefrontal cortex and the hippocampus.
Now, with declining efficacy of the prefrontal cortex and the medial temporal lobe, along with overall shrinking brain volume and white-matter reduction, you can see why older adults can find it more difficult to integrate and act on the information coming in from multiple sources, and why they find multitasking especially difficult. This is why when we age, we can have a harder time both focusing and switching our attention. It’s why we get distracted. And it’s why we have trouble dealing with new technology, especially new cell phones: The brain has slowed down, it’s smaller, and the shaping of our brains by repeated exposure to existing structures in the environment has made it easier to deal with familiar situations but harder to deal with new ones.
You can try out this slowing down yourself. Hold a pen upright, pinched between your thumb and forefinger near the writing end of the instrument. Open your grip and then, as the pen is falling, try to grab it as quickly as you can, and measure how much of the pen passed through your fingers. Compare this to what younger people can do, or make a monthly log to see if you can stay quick or start to slow down.
One of the most important things we can do to promote neural health involves myelin, which is 80 percent lipids. Our bodies’ ability to create and maintain myelin relies on dietary fats. Without them, or with a reduced ability to metabolize them, we see even more decay of the myelin sheath than is caused by aging alone. Not every word retrieval problem or lost wallet is due to demyelination, but improving and maintaining myelination does help. Two easy mechanisms are eating fatty fish and getting enough vitamin B12. You may have heard the expression that fish is brain food, and that’s true. Fish oil provides the omega-3 fatty acids that the body uses to create myelin, and it can even repair damaged myelin caused by traumatic brain injury.
The cumulative effects of aging include everything from repeated exposure to toxins, illness, and the breakdown of DNA. There are a number of things that can damage DNA—tobacco smoke, ultraviolet rays from suntanning or tanning booths, certain drugs, and even stress. Fortunately, our bodies have sophisticated DNA repair mechanisms that can detect damage and fix it. But the repair mechanisms aren’t perfect. The instructions for how the repair mechanisms work are themselves contained within DNA, so if those get damaged . . . well, you can see what the problem would be.
Up to this point I’ve glossed over the term attention, assuming (as William James did) that everyone knows what it is. We experience different modes of attention throughout the day. Two of the most noticeable are what neuroscientists call the central executive mode and the default, or resting-state mode. In the central executive mode we are focused, we direct our thoughts and filter our distractions. In the resting-state mode, our thoughts meander, they are loosely connected, and this has led to its being called the “daydreaming mode” of the brain. The daydreaming mode is restorative after you’ve been focusing on something intensely for a while, and it is often the mode during which you can effectively solve problems. If you’ve ever been walking down the breakfast cereal aisle in the grocery store, not thinking about anything in particular, and the solution to a problem you’ve been struggling with suddenly appears in your head, that’s the daydreaming mode. The two modes tend to work in opposition, like a seesaw—when one is up, the other is down. Disruptions of this daydreaming mode have been seen in individuals with autism, and those with Alzheimer’s.
Mild Cognitive Impairment, Alzheimer’s Disease, and Dementia
Mild cognitive impairment is defined as cognitive decline greater than what would normally be expected for an individual’s age and education level but that does not interfere notably with activities of daily life. In about 50 percent of patients it leads to Alzheimer’s disease (AD) and can be an early warning sign for it; other times it exists independently. That is, some mild cognitive impairment patients will maintain the same level of impairment for many years (good news), whereas for others it is a transitional stage toward dementia. People with mild cognitive impairment can still perform daily chores and look after themselves, but they have difficulties with memory and misplacing things. (Actually, that’s a good description of most of the scientists I know, even ones in their forties!)
We haven’t found a single brain correlate for mild cognitive impairment, making its neuroanatomical basis heterogeneous—that is, a number of different brain conditions could lead to it. And just when you observe systematic changes in the brain for people with mild cognitive impairment, brain scans show highly similar lesions in the brains of people who show no symptoms at all! This is similar to dementia—there is no single neurophysiological profile because it arises from a large number of different brain abnormalities.
As I write this, a new paper was just published by a group of neuroscientists in China that decomposed brain imaging signals into distinct frequency bands, and using this new technique, the neuroscientists were able to classify individuals with mild cognitive impairment with 93 percent accuracy. This is only a single paper and further work will need to be done to confirm the accuracy and utility of this, but it is a promising start.
The kinds of redundancies that exist in the brain, and the concept of cognitive reserve, may be just as important as what is actually showing up in those scans. Cognitive reserve is the idea that people with more education and who are more intelligent may be able to withstand biological degradation better than others. Cognitive reserve is like that extra secret gas tank that Volkswagens used to have in the old days (how ingenious was that?). It is the capacity of the mature brain to roll with the punches, to sustain the effects of disease or injury that would otherwise impair others.
Think about it in terms of strength or endurance in physical activity. If you can lift two hundred pounds or run for twenty minutes at top speed, it will not exert you to lift fifty pounds or run for five minutes, compared to someone who is out of shape. And even with a cold, something that impairs your muscle tone and lung capacity, you would still likely be able to outperform others. That’s the concept of reserve.
Dementia is a catchall term used to describe any brain disorder that causes deficits in more than one cognitive domain, such as attention, memory, and language. Alzheimer’s is a form of dementia, and there are many other types.
Alzheimer’s is characterized by abnormal protein aggregates (plaques) and neurofibrillary tangles, which disrupt neural transmission. One particular protein, called beta-amyloid, starts out by destroying synapses before it clumps into plaques that cause neuronal death. The disease typically starts in the medial temporal lobe and then spreads throughout much of the brain. Damage is particularly likely to affect regions linked to learning and memory, for reasons we don’t yet understand. Early symptoms include memory impairment, particularly for recent events, but then other cognitive disorders begin to appear, such as problems in attention, language, and spatial processing. There is a genetic factor, though as with virtually all disorders, the extent to which you take care of your body influences the degree and extent of the disease.
I’d like to be able to report that after the $1.8 billion the United States spent in 2018 alone, and decades of research, we know what causes Alzheimer’s, how to cure it, and how to prevent it. For a while we thought that the accumulation of amyloid was the problem, and if we could reduce it, we’d have a cure. There are now drugs that reduce amyloid buildup, but they don’t stop or reverse the disease. No drugs have managed to even improve symptoms modestly. And not everyone with these amyloid plaques and tangles has the disease or the symptoms of it. Many normal, apparently healthy human brains show the buildup of beta-amyloid plaque deposits, the loss of neural connections, and the degradation of myelinated pathways (white matter) and remain symptom-free.
Some early evidence suggests that chronic inflammatory processes feed existing Alzheimer’s disease, or perhaps even cause it. Some researchers have suggested that taking NSAIDs (nonsteroidal anti-inflammatory drugs) as much as ten years before the expected onset of Alzheimer’s symptoms might be advisable, but a great deal of further work needs to be done—we don’t know what other negative effects may accrue from such chronic use of NSAIDs.
If you’re one of the millions of people who have sent away saliva samples for commercial genetic testing, you may have received a report on a particular genetic factor that can predict the likelihood of developing dementia. The APOE gene is a genetic factor that greatly increases the risk of developing dementia, as well as late-onset Alzheimer’s disease (after the age of sixty-five). The problem with such information is that genetic contributions to dementia are complex; interactions with other genes and other biomarkers need to be taken into account in order to get an accurate picture. APOE alone does not cause dementia or Alzheimer’s. And, of course, an increased risk does not mean you’ll develop the disease with perfect certainty, and in some groups, the presence of the gene is protective. I find this information does more harm than good in people who lack advanced training in statistics and risk analysis—that is, most of us. As I described in my book The Organized Mind, some things you do can triple your risk of certain rare diseases. That means one thing if your chance of getting the disease was one in three to begin with—you’re going from a possibility of getting it to a near certainty. But if your chance of getting the disease was one in 60 million to begin with, and you triple your risk, you still only have one chance in 20 million of getting it—you’re more likely to get hit by lightning, win the lottery, and die in a car crash all on the same day.
I want to join John Zeisel, founder of the I’m Still Here Foundation, and say that the biggest challenge faced by dementia is the public narrative of despair, that nothing can be done about it. I do not believe that this is true. I believe we should replace the stigmatization of dementia with hope, and the recognition that people with dementia are still there.
The Lancet’s expert panel provides some hope. As they state,
Dementia is by no means an inevitable consequence of reaching retirement age, or even of entering the ninth decade. There are lifestyle factors that may reduce, or increase, an individual’s risk of developing dementia. In some populations dementia is already being delayed for years. . . . One-third of dementia cases may be preventable.
Stroke
A stroke is the restriction of blood flow in the brain that causes cell death. Strokes come in three types. When a clot forms in the brain, preventing oxygenated blood from reaching particular regions, it’s called an ischemic stroke. (Ischemia is the word used for restrictions of blood supply.) If the clot is only temporary, the resulting stroke is called a transient ischemic attack, or TIA. These are usually warning signs for subsequent strokes. When a weakened blood vessel in the brain bursts and causes internal bleeding, it’s called a hemorrhagic stroke. (A hemorrhage is the escape of blood from a blood vessel.)
The main risk factor for any type of stroke is high blood pressure. Antihypertensives are prescribed therefore not just to reduce the risk of cardiac disease but to reduce the risk of stroke, especially in people who have other risk factors, such as obesity, poor health, or a family history of stroke. Lifestyle interventions, such as restricting salt intake, learning to cope with stress, and aerobic exercise also lower blood pressure.
For years, doctors advised people over fifty or sixty to take a baby aspirin (around 80 mg) every day as a preventative, to thin the blood, thus reducing the risk of a blood clot or ischemic stroke. The problem with this is that if you have a hemorrhagic stroke, the thin blood won’t clot and the damage from internal bleeding will be more severe. It’s one of those weird situations in medicine where you effectively have to choose how you want to die or be otherwise damaged: Would I rather have the damage from a clot or from a rupture? On the other hand, if you’ve already experienced an ischemic stroke—and you know for sure that it was ischemic and not hemorrhagic—taking aspirin or other blood thinners is usually advised to reduce the chance of a second ischemic stroke. As of 2019, there is mounting evidence that taking the low dose aspirin is preventively not worth the risk, and a study of twelve thousand Europeans found that it had no effect on stroke.
The aftermath of stroke is highly variable. Some people experience no aftereffects at all; others are left partially paralyzed, are unable to speak, or experience profound personality changes. In some cases, cognitive and physical therapy can restore function to nearly 100 percent, but we still don’t know which patients will recover fully and which will not. Genetics, resilience, determination, and environmental factors all play a role, but we have not yet elucidated the how or the why.
Neuroplasticity across the Life Span
For decades, physicians and scientists assumed that our brains are built from a finite number of “cells,” each with its own job to do, and after the brain reaches maturity, we lose cells one by one until we end up in a second infancy. Although we generally believed this, we had inklings that it wasn’t true. Neuroscientist Karl Lashley argued eighty years ago that if part of the brain was damaged, other brain areas would take over, but the idea of the brain as an immutable machine held sway. As explained by physician Abigail Zuger, “Every part had a specific purpose, none could be replaced or repaired. . . . Now sophisticated experimental techniques suggest the brain is more like a Disney-esque animated sea creature. Constantly oozing in various directions, it is apparently able to respond to injury with striking functional reorganization, and can at times actually think itself into a new anatomic configuration.”
Along these same lines, scientists used to think that the human brain couldn’t grow any new neurons after birth. Then, evidence emerged that neurogenesis—the growth of new neurons—occurred in the hippocampus of adults, and some estimates placed the number at seven hundred new neurons per day. That is not a lot considering that the hippocampus is estimated to have around 47 million neurons; it represents the growth of around 1.5 percent of the total number of neurons each year. Then, in 2018, two studies were published in the same month that reached opposite conclusions. One study, published in Nature, from the University of California, San Francisco, showed that hippocampal neurogenesis drops to undetectable levels in childhood. Another study, from Columbia University, found preserved neurogenesis in adults.
Two review papers that year attempted to resolve the contradiction. There are a number of complex technical and methodological challenges to measuring neuronal growth, and since neurons can’t be physically counted in humans (yet), the estimates rely on a number of inferences, both conceptual and statistical. Both teams used the presence of protein markers (DCX and PSA-NCAM) that typically accompany neuronal growth. These markers can only be measured in autopsies, and variations in how brains are preserved and the delay between time of death and time of examination could yield such wildly contradictory results. In addition, some studies have found that, in animals, the growth of new neurons isn’t necessarily accompanied by these protein markers. Confused yet? So am I and other neuroscientists. The field is still working all this out, and so at present, I’d have to say we don’t really know if adult humans can grow new hippocampal neurons. But the weight of the evidence, spanning the past twenty years of research, strongly suggests we do. A single study that fails to find growth isn’t sufficient to negate a dozen other studies that did, or the dozens of studies in animals that show they continue to grow new neurons—there is no reason we know of that humans would be different. But even the lack of neurogenesis doesn’t mean we don’t form new memories, or that our memory capacity is limited. Memory resides in the connections between neurons, and in synaptic plasticity, which is a lifelong process.
The Canadian psychiatrist Norman Doidge describes case studies of individuals who experienced this kind of synaptic plasticity, a rewiring of their brains, from a woman with a damaged vestibular (balance) system to a man suffering phantom pain in a limb that had been amputated—all achieved functional reorganizations of their brains as adults.
I had been taught in 1976 that this kind of neuroplasticity peaked in adolescence and young adulthood, that sixty-plus-year-olds could not hope to experience such complete and rapid remodeling of their brains. But research in the past ten years has shown these assumptions to be wrong. Older adults’ brains are plastic, capable of great feats of rewiring and adaptation; it just takes a little longer because much (but not everything) that older brains do is slowed down.
Neuroplasticity does not seem to slow down nearly as much for older adults who have been making demands on their brains to think differently and rewire for many years. If you’re involved in the creative arts—painting, sculpture, architecture, dance, writing, music, and other forms of creativity—you’ve been exercising your brain, pushing your brain, in interesting ways all along because every project you undertake requires new adaptations, some way of looking at the world differently, and then acting on it. And it’s not limited to the creative arts—any job or hobby that requires you to interact with the world and to respond to it differently each time is an activity that helps protect the brain against dementia, rigidity, and neural atrophy. This can apply to housepainters, arborists, athletes, serial entrepreneurs, publicists, professional drivers, crossword puzzle players, bridge players, and so on.
My own experience with musical instruments shows this remodeling can occur at any age. Sometimes at a concert, musician friends call me up onstage to perform a song or two, and I play whatever guitar is already there. Every guitar is different and I typically face parameters I’m not used to—differences in the height of the frets, the distance between the strings, the gauge of the strings, and the thickness of the neck. Or I might be handed an acoustic after having played electric guitar for several months. The adaptation is almost immediate. A musician’s brain contains an abstract representation of how their instruments are supposed to work, and how their fingers are supposed to interact with them, and it makes appropriate adjustments. Even more sophisticated is what happened when I broke a nail the other day on the middle finger of my right hand, my fingerpicking hand. I just “told myself” that this finger was out of commission and shifted to the next two fingers down the line everything that this finger used to do. It took all of five minutes to make the adjustment, an example of neuroplasticity. Mari Kodama, the great concert pianist, says that she often has to change well-rehearsed fingerings on the spot during a performance, depending on the piano or the acoustics of the hall. So although we have finger patterns deeply memorized, abstractions of those patterns are apparently memorized as well and are there to be tapped into.
You’ve probably experienced this yourself in daily activities and not even known that it was something as lofty as neuroplasticity or brain adaptation: driving a rental car, using a pen with a body of a different thickness than you’ve used before, cooking in someone else’s kitchen, buttoning up a new shirt, listening to someone speak in an accent you’ve never heard before. Even something as simple as drinking coffee out of a new cup that is weighted differently and has a differently sized handle than you’re used to. These are all examples of adaptive neuroplasticity.
Neuroplasticity continues until we die, but, like reaction times, it does slow down, and the extent to which brain remodeling can occur is reduced as we age. The good news is that previously learned motor skills are well-preserved at least through age sixty and for many well beyond their eighties. The musician Glen Campbell is a prime example. At age seventy-six, deeply affected by Alzheimer’s disease, disoriented and unable to take care of himself, he was still performing complex songs that he had known for more than forty-five years, which underscores how certain remarkable motor routines are embedded deep in memory where disease can’t touch them. Other motor routines fly off the rails, and Campbell would sometimes lose his place and not know how to get back. One of the most protective things you can do against aging is to learn a manual skill when you’re young and keep it up. The next best thing you can do is to start learning something new when you’re old.
The efficiency with which we learn new motor skills, however, declines with age—we can learn well into our nineties and beyond, but the learning takes more concentration and more time. In what has become a familiar conversation between grandparents and their grandchildren, older adults can learn how to use computers and cell phones, but they make more errors while they’re learning and don’t retain the new information as long as younger people. In adapting to new glasses, or shoes, or directions due to roadwork, older adults take longer, and longer as well to readapt to the previous way of doing things. It’s not just that older adults are slower at doing many things; it’s that they are slower at adjusting to new things. If you are thinking that there might be a correlation between this and the tendency for older adults to become more politically conservative—to want things to stay the way they are—you might be on to something.
Our senses are among the earliest things to emerge in the womb, but unfortunately they can wear out sooner than many of our other faculties, as we’ve seen in older adults. Half of adults over the age of seventy-five report hearing loss and one in six report vision loss. A whopping 90 percent of people over the age of fifty-five wear glasses; only one in six Americans with hearing loss wears hearing aids, and not wearing hearing aids is associated with an increased risk of hospitalization in older adults. Fortunately, neuroplasticity offers the brain a number of ways to compensate for the decline in the quality of sensory information. Neuroplasticity leverages what our bodies can tell us about the world, how and how well our senses perceive it. Understanding how perception works and develops is essential to understanding successful aging.