Behave: The Biology of Humans at Our Best and Worst

by Robert M. Sapolsky

  All of that was eventually shown—there’s considerable adult neurogenesis in the hippocampus (where roughly 3 percent of neurons are replaced each month) and lesser amounts in the cortex.22 It happens in humans throughout adult life. Hippocampal neurogenesis, for example, is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury* and inhibited by various stressors.*23 Moreover, the new hippocampal neurons integrate into preexisting circuits, with the perky excitability of young neurons in the perinatal brain. Most important, new neurons are essential for integrating new information into preexisting schemas, something called “pattern separation.” This is when you learn that two things you previously thought were the same are, in fact, different—dolphins and porpoises, baking soda and baking powder, Zooey Deschanel and Katy Perry.

  Adult neurogenesis is the trendiest topic in neuroscience. In the five years after Altman’s 1965 paper was published, it was cited (a respectable) twenty-nine times in the literature; in the last five, more than a thousand. Current work examines how exercise stimulates the process (probably by increasing levels of certain growth factors in the brain), how new neurons know where to migrate, whether depression is caused by a failure of hippocampal neurogenesis, and whether the neurogenesis stimulated by antidepressants is required for such medications to work.24

  Why did it take so long for adult neurogenesis to be accepted? I’ve interacted with many of the principals and am struck by their differing takes. At one extreme is the view that while skeptics like Rakic were ham-handed, they provided quality control and that, counter to how path-of-the-hero epics go, some early work in the field was not all that solid. At the other extreme is the view that Rakic et al., having failed to find adult neurogenesis, couldn’t accept that it existed. This psychohistorical view, of the old guard clinging to dogma in the face of changing winds, is weakened a bit by Altman’s not having been a young anarchist running amok in the archives; in fact, he is a bit older than Rakic and other principal skeptics. All of this needs to be adjudicated by historians, screenwriters, and soon, I hope, by the folks in Stockholm.

  Altman, who at the time of this writing is eighty-nine, published a 2011 memoir chapter.25 Parts of it have a plaintive, confused tone—everyone was so excited at first; what happened? Maybe he spent too much time in the lab and too little marketing the discovery, he suggests. There’s the ambivalence of someone who spent a long time as a scorned prophet who at least got to be completely vindicated. He’s philosophical about it—hey, I’m a Hungarian Jew who escaped from a Nazi camp; you take things in stride after that.

  SOME OTHER DOMAINS OF NEUROPLASTICITY

  We’ve seen how in adults experience can alter the number of synapses and dendritic branches, remap circuitry, and stimulate neurogenesis.26 Collectively, these effects can be big enough to actually change the size of brain regions. For example, postmenopausal estrogen treatment increases the size of the hippocampus (probably through a combination of more dendritic branches and more neurons). Conversely, the hippocampus atrophies (producing cognitive problems) in prolonged depression, probably reflecting its stressfulness and the typically elevated glucocorticoid levels of the disease. Memory problems and loss of hippocampal volume also occur in individuals with severe chronic pain syndromes, or with Cushing’s syndrome (an array of disorders where a tumor causes extremely elevated glucocorticoid levels). Moreover, post-traumatic stress disorder is associated with increased volume (and, as we know, hyperreactivity) of the amygdala. In all of these instances it is unclear how much the stress/glucocorticoid effects are due to changes in neuron number or to changes in amounts of dendritic processes.*

  One cool example of the size of a brain region changing with experience concerns the back part of the hippocampus, which plays a role in memory of spatial maps. Cab drivers use spatial maps for a living, and one renowned study showed enlargement of that part of the hippocampus in London taxi drivers. Moreover, a follow-up study imaged the hippocampus in people before and after the grueling multiyear process of working and studying for the London cabbie license test (called the toughest test in the world by the New York Times). The hippocampus enlarged over the course of the process—in those who passed the test.27

  Thus, experience, health, and hormone fluctuations can change the size of parts of the brain in a matter of months. Experience can also cause long-lasting changes in the numbers of receptors for neurotransmitters and hormones, in levels of ion channels, and in the state of on/off switches on genes in the brain (to be covered in chapter 8).28

  With chronic stress the nucleus accumbens is depleted of dopamine, biasing rats toward social subordination and biasing humans toward depression. As we saw in the last chapter, if a rodent wins a fight on his home territory, there are long-lasting increases in levels of testosterone receptors in the nucleus accumbens and ventral tegmentum, enhancing testosterone’s pleasurable effects. There’s even a parasite called Toxoplasma gondii that can infect the brain; over the course of weeks to months, it makes rats less fearful of the smell of cats and makes humans less fearful and more impulsive in subtle ways. Basically, most anything you can measure in the nervous system can change in response to a sustained stimulus. And importantly, these changes are often reversible in a different environment.*

  SOME CONCLUSIONS

  The discovery of adult neurogenesis is revolutionary, and the general topic of neuroplasticity, in all its guises, is immensely important—as is often the case when something the experts said couldn’t be turns out to be.29 The subject is also fascinating because of the nature of the revisionism—neuroplasticity radiates optimism. Books on the topic are entitled The Brain That Changes Itself, Train Your Mind, Change Your Brain, and Rewire Your Brain: Think Your Way to a Better Life, hinting at the “new neurology” (i.e., no more need for neurology once we can fully harness neuroplasticity). There’s can-do Horatio Alger spirit every which way you look.

  Amid that, some cautionary points:

  One recalls caveats aired in other chapters—the ability of the brain to change in response to experience is value free. Axonal remapping in blind or deaf individuals is great, exciting, and moving. It’s cool that your hippocampus expands if you drive a London cab. Ditto about the size and specialization of the auditory cortex in the triangle player in the orchestra. But at the other end, it’s disastrous that trauma enlarges the amygdala and atrophies the hippocampus, crippling those with PTSD. Similarly, expanding the amount of motor cortex devoted to finger dexterity is great in neurosurgeons but probably not a societal plus in safe crackers.

  The extent of neuroplasticity is most definitely finite. Otherwise, grievously injured brains and severed spinal cords would ultimately heal. Moreover, the limits of neuroplasticity are quotidian. Malcolm Gladwell has explored how vastly skilled individuals have put in vast amounts of practice—ten thousand hours is his magic number. Nevertheless, the reverse doesn’t hold: ten thousand hours of practice does not guarantee the neuroplasticity needed to make any of us a Yo-Yo Ma or LeBron James.

  Manipulating neuroplasticity for recovery of function does have enormous, exciting potential in neurology. But this domain is far from the concerns of this book. Despite neuroplasticity’s potential, it’s unlikely that we’ll ever be able to, say, spritz neuronal growth factors up people’s noses to make them more open-minded or empathic, or to target neuroplasticity with gene therapy to blunt some jerk’s tendency to displace aggression.

  So what’s the subject good for in the realm of this book? I think the benefits are mostly psychological. This recalls a point from chapter 2, in the discussion of the neuroimaging studies demonstrating loss of volume in the hippocampus of people with PTSD (certainly an example of the adverse effects of neuroplasticity). I sniped that it was ridiculous that many legislators needed pictures of the brain to believe that there was something desperately, organically wrong with veterans with PTSD.

  Similarly, neuropla
sticity makes the functional malleability of the brain tangible, makes it “scientifically demonstrated” that brains change. That people change. In the time span considered in this chapter, people throughout the Arab world went from being voiceless to toppling tyrants; Rosa Parks went from victim to catalyst, Sadat and Begin from enemies to architects of peace, Mandela from prisoner to statesman. And you’d better bet that changes along the lines of those presented in this chapter occurred in the brains of anyone transformed by these transformations. A different world makes for a different worldview, which means a different brain. And the more tangible and real the neurobiology underlying such change seems, the easier it is to imagine that it can happen again.

  Six

  Adolescence; or, Dude, Where’s My Frontal Cortex?

  This chapter is the first of two focusing on development. We’ve established our rhythm: a behavior has just occurred; what events in the prior seconds, minutes, hours, and so on helped bring it about? The next chapter extends this into the developmental domain—what happened during that individual’s childhood and fetal life that contributed to the behavior?

  The present chapter breaks this rhythm in focusing on adolescence. Does the biology introduced in the preceding chapters work differently in an adolescent than in an adult, producing different behaviors? Yes.

  One fact dominates this chapter. Chapter 5 did in the dogma that adult brains are set in stone. Another dogma was that brains are pretty much wired up early in childhood—after all, by age two, brains are already about 85 percent of adult volume. But the developmental trajectory is much slower than that. This chapter’s key fact is that the final brain region to fully mature (in terms of synapse number, myelination, and metabolism) is the frontal cortex, not going fully online until the midtwenties.1

  This has two screamingly important implications. First, no part of the adult brain is more shaped by adolescence than the frontal cortex. Second, nothing about adolescence can be understood outside the context of delayed frontocortical maturation. If by adolescence limbic, autonomic, and endocrine systems are going full blast while the frontal cortex is still working out the assembly instructions, we’ve just explained why adolescents are so frustrating, great, asinine, impulsive, inspiring, destructive, self-destructive, selfless, selfish, impossible, and world changing. Think about this—adolescence and early adulthood are the times when someone is most likely to kill, be killed, leave home forever, invent an art form, help overthrow a dictator, ethnically cleanse a village, devote themselves to the needy, become addicted, marry outside their group, transform physics, have hideous fashion taste, break their neck recreationally, commit their life to God, mug an old lady, or be convinced that all of history has converged to make this moment the most consequential, the most fraught with peril and promise, the most demanding that they get involved and make a difference. In other words, it’s the time of life of maximal risk taking, novelty seeking, and affiliation with peers. All because of that immature frontal cortex.

  THE REALITY OF ADOLESCENCE

  Is adolescence real? Is there something qualitatively different distinguishing it from before and after, rather than being part of a smooth progression from childhood to adulthood? Maybe “adolescence” is just a cultural construct—in the West, as better nutrition and health resulted in earlier puberty onset, and the educational and economic forces of modernity pushed for childbearing at later ages, a developmental gap emerged between the two. Voilà! The invention of adolescence.*2

  As we’ll see, neurobiology suggests that adolescence is for real, that the adolescent brain is not merely a half-cooked adult brain or a child’s brain left unrefrigerated for too long. Moreover, most traditional cultures do recognize adolescence as distinct, i.e., it brings some but not all of the rights and responsibilities of adulthood. Nonetheless, what the West invented is the longest period of adolescence.*

  What does seem a construct of individualistic cultures is adolescence as a period of intergenerational conflict; youth of collectivist cultures seem less prone toward eye rolling at the dorkiness of adults, starting with parents. Moreover, even within individualistic cultures adolescence is not universally a time of acne of the psyche, of Sturm und Drang. Most of us get through it just fine.

  THE NUTS AND BOLTS OF FRONTAL CORTICAL MATURATION

  The delayed maturation of the frontal cortex suggests an obvious scenario, namely that early in adolescence the frontal cortex has fewer neurons, dendritic branches, and synapses than in adulthood, and that levels increase into the midtwenties. Instead, levels decrease.

  This occurs because of a truly clever thing evolved by mammalian brains. Remarkably, the fetal brain generates far more neurons than are found in the adult. Why? During late fetal development, there is a dramatic competition in much of the brain, with winning neurons being the ones that migrate to the correct location and maximize synaptic connections to other neurons. And neurons that don’t make the grade? They undergo “programmed cell death”—genes are activated that cause them to shrivel and die, their materials then recycled. Neuronal overproduction followed by competitive pruning (which has been termed “neural Darwinism”) allowed the evolution of more optimized neural circuitry, a case of less being more.

  The same occurs in the adolescent frontal cortex. By the start of adolescence, there’s a greater volume of gray matter (an indirect measure of the total number of neurons and dendritic branches) and more synapses than in adults; over the next decade, gray-matter thickness declines as less optimal dendritic processes and connections are pruned away.*3 Within the frontal cortex, the evolutionarily oldest subregions mature first; the spanking-new (cognitive) dorsolateral PFC doesn’t even start losing gray-matter volume until late adolescence. The importance of this developmental pattern was shown in a landmark study in which children were neuroimaged and IQ tested repeatedly into adulthood. The longer the period of packing on gray-matter cortical thickness in early adolescence before the pruning started, the higher the adult IQ.

  Thus, frontal cortical maturation during adolescence is about a more efficient brain, not more brain. This is shown in easily misinterpreted neuroimaging studies comparing adolescents and adults.4 A frequent theme is how adults have more executive control over behavior during some tasks than do adolescents and show more frontal cortical activation at the time. Now find a task where, atypically, adolescents manage a level of executive control equal to that of adults. In those situations adolescents show more frontal activation than adults—equivalent regulation takes less effort in a well-pruned adult frontal cortex.

  That the adolescent frontal cortex is not yet lean and mean is demonstrable in additional ways. For example, adolescents are not at adult levels of competence at detecting irony and, when trying to do so, activate the dmPFC more than do adults. In contrast, adults show more activation in the fusiform face region. In other words, detecting irony isn’t much of a frontal task for an adult; one look at the face is enough.5

  What about white matter in the frontal cortex (that indirect measure of myelination of axons)? Here things differ from the overproduce-then-prune approach to gray matter; instead, axons are myelinated throughout adolescence. As discussed in appendix 1, this allows neurons to communicate in a more rapid, coordinated manner—as adolescence progresses, activity in different parts of the frontal cortex becomes more correlated as the region operates as more of a functional unit.6

  This is important. When learning neuroscience, it’s easy to focus on individual brain regions as functionally distinct (and this tendency worsens if you then spend a career studying just one of them). As a measure of this, there are two high-quality biomedical journals out there, one called Cortex, the other Hippocampus, each publishing papers about its favorite brain region. At neuroscience meetings attended by tens of thousands, there’ll be social functions for all the people studying the same obscure brain region, a place where they can gossip and bond and court. But in reality the brain
is about circuits, about the patterns of functional connectivity among regions. The growing myelination of the adolescent brain shows the importance of increased connectivity.

  Interestingly, other parts of the adolescent brain seem to help out the underdeveloped frontal cortex, taking on some roles that it’s not yet ready for. For example, in adolescents but not adults, the ventral striatum helps regulate emotions; we will return to this.7

  Something else keeps that tyro frontal cortex off-kilter, namely estrogen and progesterone in females and testosterone in males. As discussed in chapter 4, these hormones alter brain structure and function, including in the frontal cortex, where gonadal hormones change rates of myelination and levels of receptors for various neurotransmitters. Logically, landmarks of adolescent maturation in brain and behavior are less related to chronological age than to the time since puberty onset.8

  Moreover, puberty is not just about the onslaught of gonadal hormones. It’s about how they come online.9 The defining feature of ovarian endocrine function is the cyclicity of hormone release—“It’s that time of the month.” In adolescent females puberty does not arrive full flower, so to speak, with one’s first period. Instead, for the first few years only about half of cycles actually involve ovulation and surges of estrogen and progesterone. Thus, not only are young adolescents experiencing these first ovulatory cycles, but there are also higher-order fluctuations in whether the ovulatory fluctuation occurs. Meanwhile, while adolescent males don’t have equivalent hormonal gyrations, it can’t help that their frontal cortex keeps getting hypoxic from the priapic blood flow to the crotch.