06-adolescence

T Six Adolescence; or, Dude, Where’s My Frontal Cortex? his 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. I THE REALITY OF ADOLESCENCE s 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. T THE NUTS AND BOLTS OF FRONTAL CORTICAL MATURATION he 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. Thus, as adolescence dawns, frontal cortical efficiency is diluted with extraneous synapses failing to make the grade, sluggish communication thanks to undermyelination, and a jumble of uncoordinated subregions working at cross-purposes; moreover, while the striatum is trying to help, a pinch hitter for the frontal cortex gets you only so far. Finally, the frontal cortex is being pickled in that ebb and flow of gonadal hormones. No wonder they act adolescent. Frontal Cortical Changes in Cognition in Adolescence To appreciate what frontal cortical maturation has to do with our best and worst behaviors, it’s helpful to first see how such maturation plays out in cognitive realms. During adolescence there’s steady improvement in working memory, flexible rule use, executive organization, and frontal inhibitory regulation (e.g., task shifting). In general, these improvements are accompanied by increasing activity in frontal regions during tasks, with the extent of the increase predicting accuracy.10 Adolescents also improve at mentalization tasks (understanding someone else’s perspective). By this I don’t mean emotional perspective (stay tuned) but purer cognitive challenges, like understanding what objects look like from someone else’s perspective. The improvement in detecting irony reflects improvement in abstract cognitive perspective taking. Frontal Cortical Changes in Emotional Regulation Older teenagers experience emotions more intensely than do children or adults, something obvious to anyone who ever spent time as a teenager. For example, they are more reactive to faces expressing strong emotions.11 In adults, looking at an “affective facial display” activates the amygdala, followed by activation of the emotion-regulating vmPFC as they habituate to the emotional content. In adolescence, though, the vmPFC response is less; thus the amygdaloid response keeps growing. Chapter 2 introduced “reappraisal,” in which responses to strong emotional stimuli are regulated by thinking about them differently.12 Get a bad grade on an exam, and there’s an emotional pull toward “I’m stupid”; reappraisal might lead you instead to focus on your not having studied or having had a cold, to decide that the outcome was situational, rather than a function of your unchangeable constitution. Reappraisal strategies get better during adolescence, with logical neurobiological underpinnings. Recall how in early adolescence, the ventral striatum, trying to be helpful, takes on some frontal tasks (fairly ineffectively, as it’s working above its pay grade). At that age reappraisal engages the ventral striatum; more activation predicts less amygdaloid activation and better emotional regulation. As the adolescent matures, the prefrontal cortex takes over the task, and emotions get steadier.13 Bringing the striatum into the picture brings up dopamine and reward, thus bringing up the predilection of adolescents for bungee jumping. I ADOLESCENT RISK TAKING n the foothills of the Sierras are California Caverns, a cave system that leads, after an initial narrow, twisting 30-foot descent down a hole, to an abrupt 180-foot drop (now navigable by rappelling). The Park Service has found skeletons at the bottom dating back centuries, explorers who took one step too far in the gloom. And the skeletons are always those of adolescents. As shown experimentally, during risky decision making, adolescents activate the prefrontal cortex less than do adults; the less activity, the poorer the risk assessment. This poor assessment takes a particular form, as shown by Sarah- Jayne Blakemore of University College London.14 Have subjects estimate the likelihood of some event occurring (winning the lottery, dying in a plane crash); then tell them the actual likelihood. Such feedback can constitute good news (i.e., something good is actually more likely than the person estimated, or something bad is less likely). Conversely, the feedback can constitute bad news. Ask subjects to estimate the likelihood of the same events again. Adults incorporate the feedback into the new estimates. Adolescents update their estimates as adults do for good news, but feedback about bad news barely makes a dent. (Researcher: “How likely are you to have a car accident if you’re driving while drunk?” Adolescent: “One chance in a gazillion.” Researcher: “Actually, the risk is about 50 percent; what do you think your own chances are now?” Adolescent: “Hey, we’re talking about me; one chance in a gazillion.”) We’ve just explained why adolescents have two to four times the rate of pathological gambling as do adults.15 So adolescents take more risks and stink at risk assessment. But it’s not just that teenagers are more willing to take risks. After all, adolescents and adults don’t equally desire to do something risky and the adults simply don’t do it because of their frontal cortical maturity. There is an age difference in the sensations sought—adolescents are tempted to bungee jump; adults are tempted to cheat on their low-salt diet. Adolescence is characterized not only by more risking but by more novelty seeking as well.16 Novelty craving permeates adolescence; it is when we usually develop our stable tastes in music, food, and fashion, with openness to novelty declining thereafter.17 And it’s not just a human phenomenon. Across the rodent life span, it’s adolescents who are most willing to eat a new food. Adolescent novelty seeking is particularly strong in other primates. Among many social mammals, adolescents of one sex leave their natal group, emigrating into another population, a classic means to avoid inbreeding. Among impalas there are groups of related females and offspring with one breeding male; the other males knock around disconsolately in “bachelor herds,” each scheming to usurp the breeding male. When a young male hits puberty, he is driven from the group by the breeding male (and to avoid some Oedipus nonsense, this is unlikely to be his father, who reigned many breeding males ago). But not among primates. Take baboons. Suppose two troops encounter each other at some natural boundary—say, a stream. The males threaten each other for a while, eventually get bored, and resume whatever they were doing. Except there’s an adolescent, standing at the stream’s edge, riveted. New baboons, a whole bunch of ’em! He runs five steps toward them, runs back four, nervous, agitated. He gingerly crosses and sits on the other bank, scampering back should any new baboon glance at him. So begins the slow process of transferring, spending more time each day with the new troop until he breaks the umbilical cord and spends the night. He wasn’t pushed out. Instead, if he has to spend one more day with the same monotonous baboons he’s known his whole life, he’ll scream. Among adolescent chimps it’s females who can’t get off the farm fast enough. We primates aren’t driven out at adolescence. Instead we desperately crave novelty.* Thus, adolescence is about risk taking and novelty seeking. Where does the dopamine reward system fit in? Recall from chapter 2 how the ventral tegmentum is the source of the mesolimbic dopamine projection to the nucleus accumbens, and of the mesocortical dopamine projection to the frontal cortex. During adolescence, dopamine projection density and signaling steadily increase in both pathways (although novelty seeking itself peaks at midadolescence, probably reflecting the emerging frontal regulation after that).18 Changes in the amount of dopaminergic activity in the “reward center” of the brain following different magnitudes of reward. For the adolescents, the highs are higher, the lows lower. Visit bit.ly/2o3TBI8 for a larger version of this graph. It’s unclear how much dopamine is released in anticipation of reward. Some studies show more anticipatory activation of reward pathways in adolescents than in adults, while others show the opposite, with the least dopaminergic responsiveness in adolescents who are most risk taking.19 Age differences in absolute levels of dopamine are less interesting than differences in patterns of release. In a great study, children, adolescents, and adults in brain scanners did some task where correct responses produced monetary rewards of varying sizes (see figure above).20 During this, prefrontal activation in both children and adolescents was diffuse and unfocused. However, activation in the nucleus accumbens in adolescents was distinctive. In children, a correct answer produced roughly the same increase in activity regardless of size of reward. In adults, small, medium, and large rewards caused small, medium, and large increases in accumbens activity. And adolescents? After a medium reward things looked the same as in kids and adults. A large reward produced a humongous increase, much bigger than in adults. And the small reward? Accumbens activity declined. In other words, adolescents experience bigger- than-expected rewards more positively than do adults and smaller-than-expected rewards as aversive. A gyrating top, nearly skittering out of control. This suggests that in adolescents strong rewards produce exaggerated dopaminergic signaling, and nice sensible rewards for prudent actions feel lousy. The immature frontal cortex hasn’t a prayer to counteract a dopamine system like this. But there is something puzzling. Amid their crazy, unrestrained dopamine neurons, adolescents have reasoning skills that, in many domains of perceiving risk, match those of adults. Yet despite that, logic and reasoning are often jettisoned, and adolescents act adolescent. Work by Laurence Steinberg of Temple University has identified a key juncture where adolescents are particularly likely to leap before looking: when around peers. A PEERS, SOCIAL ACCEPTANCE, AND SOCIAL EXCLUSION dolescent vulnerability to peer pressure from friends, especially peers they want to accept them as friends, is storied. It can also be demonstrated experimentally. In one Steinberg study adolescents and adults took risks at the same rate in a video driving game. Adding two peers to egg them on had no effect on adults but tripled risk taking in adolescents. Moreover, in neuroimaging studies, peers egging subjects on (by intercom) lessens vmPFC activity and enhances ventral striatal activity in adolescents but not adults.21 Why do adolescents’ peers have such social power? For starters, adolescents are more social and more complexly social than chi