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The Bounce-Back Effect 

We know fear and stress can make you sick. Researchers probe the brain to see how resilience can make you well.

By Kristin Ostberg

Adolescence is difficult everywhere, but nowhere more so than on Cayo Santiago. A thousand rhesus monkeys inhabit this tiny island paradise just off the coast of Puerto Rico, virtually unbothered by humans. When they reach adolescence, young males are subject to a treacherous social test: leaving the care of their mothers, they go out to seek their fortune, make new friends, and find their way into a new clan--and a quarter of them die trying.

Why do so many monkeys perish once they leave home? "We don't know," says Dr. Ned Kalin, who's been studying them since 1992. But he expects it has to do with their emotional dispositions, what he and his colleagues call their affective style. In this circumscribed habitat, Kalin and his fellow researchers have been following the progress of individual monkeys. They have made detailed social observations--so they know who is related to whom, who gets groomed, and who has lots of friends--and every year they administer a battery of physiological tests. They're expecting they'll find that monkeys with outgoing personalities share certain biological features, features that affect their ability to deal with the stress of leaving home.

Kalin is the director of the HealthEmotions Research Institute in Madison, Wisconsin, home to what is probably the largest concentration of emotions researchers anywhere. Affiliated with the University of Wisconsin, the institute recently received an $11 million grant from the National Institute of Mental Health for its all-fronts campaign to unravel the biology of positive and negative emotions and their impact on health. That campaign employs everything from the most basic cell biology to lab rat and primate research, human brain imaging, and long-term population studies.

Emotions researchers have traditionally focused on negative emotions: the fear, anxiety, and depression that make people sick. To try to explain the flip side--how positive emotions keep people well--researchers at Madison are looking at a constellation of qualities related to a person's ability to regulate his or her emotions and recover from negative ones, or what they call positive affective style. Generally, the monkey with the positive affective style is the one that tends to move forward in the world where others hold back. It's not that he's shallow; he still suffers from the negative emotions that afflict most primates. It's just that he gets over them faster.

Dr. Richard Davidson, Kalin's colleague and the other lead scientist at the Health-Emotions Research Institute, defines positive affective style as the "ability to feel emotions deeply but appropriately, then rapidly recover." Director of the university's W.M. Keck Laboratory for Functional Brain Imaging and Behavior, Davidson sees no reason happiness should be limited to the lucky few born with good brain chemistry or the right neural wiring. As researchers learn how affect is related to patterns of brain activity, they are also asking what determines those patterns--to what extent the code is written in the genes, and to what extent we might rewire a faulty system using medication, behavioral therapy, or meditation. "There's no reason to think of emotional reactivity as a skill any different from any other skills," Davidson told the audience at the institute's annual Symposium on Emotion this spring. He urged them to imagine the day when we could all be emotional athletes, training ourselves to be champions of positive affective style. And if you're not sure you're ready for scientists as personal trainers, plotting a mental exercise program that'll lead you to your ideal personality, you might find you can adjust to the idea quicker than you think.

For years, neuroscientists avoided emotions. They'd study sense perception, cognition, even try to put their fingers on the pulse of consciousness itself before they'd mess with the tangled circuits of affect. Partly, they didn't have the tools to measure their theories on the live human brain; they could take pictures of the brain's structure, or they could measure its activity with electrodes, but they couldn't observe brain activity as it was taking place until the advent of functional magnetic resonance imaging, a process for imaging changes in blood flow. The phenomenally expensive piece of machinery that makes fMRI work didn't come on-line for brain research until 1991.

An animal's brain is more accessible. It can be sliced into sections and treated to mark the presence of particular hormone or neurotransmitter systems. You can grind it up and separate out specific receptors, or penetrate it with surgically implanted electrodes to stimulate its various parts while you observe the animal's response. Neuroscientists have learned their way around a rat's brain so well that they can implant tiny instruments that measure the firing of specific neurons. Yet with all this technology, it's still hard to know exactly what the rat is feeling.

Beyond the practical considerations, there may be a lingering fear among scientists that emotions research isn't quite decent. Neuroscience textbooks still include a cautionary reference to phrenology, that school of 19th-century science that thought a person's character could be read from the topography of his skull. Now, even as scientists begin to be able to tease apart the brain's intricate exchanges, they're hesitant to point to any one lump or region and say, "Fear occurs here."

When psychologist Edmund Rolls went to Madison in April to speak at the Health-Emotions Research Institute's symposium (this year's topic: "The Neurobiology of Positive Emotion"), he showed a slide of the cover of his most recent book, The Brain and Emotion, featuring an illustration of Pandora and her awful box. Pandora wasn't sure if she should look into the box, he reminded his audience ominously. Are we? Then he launched into a sober discussion of whether the neurons in the orbito-frontal cortex of a rat can differentiate between the promise of a glucose and a saline reward.

Rolls's lecture may not sound very emotional, but then "emotions are states elicited by reinforcing stimuli," he says. He challenged his audience to think of an emotion that can't be traced back to reward or punishment. Our genetic codes are relatively rigid, he muses; emotions may have evolved as a sort of interface that gives an organism the flexibility to react to the vagaries of the external world.

And though not everyone at the symposium would describe emotions as operationally as Edmund Rolls, emotions research is still built on the most basic cell biology and a strong sense of evolutionary function. These scientists haven't come to Madison to delve into the nuances of sentiment; they talk about pleasure and pain, reward and reinforcement, the tendency to approach or withdraw in response to a stimulus.

So to find out when a rat is feeling anxious, the researchers at the HealthEmotions Research Institute use a maze. Some of the corridors are dark and enclosed and others are open to the light, designed to tease out the conflicting impulses in a rat. On the one hand, the bright parts are so interesting that it wants to rush out and see what's going on; on the other hand they're unknown, a little scary, and it feels more secure in the darker parts of the maze.

Researchers expose a rat to the scent of a predator, then drop it in the maze. If it retreats to the dark corners, it may be withdrawing in response to the stimulus; if it shuns the dark and makes its way out into the exposed areas, it might be feeling any variety of ways: brave, giddy, curious, or defiant. But it has apparently overcome its impulse to withdraw in response to a threatening stimulus. At least from a distance, this looks like a rat with a positive affective style.

The scientists at the HealthEmotions Research Institute aren't the first to use the approach/withdraw response as a measure of emotion, but they are doing innovative work tracking the systems that regulate this response. In fact, they argue, there are two distinct pathways in the brain--one that activates the emotion, and one that effectively decides when to shut it off. Kalin and Davidson have split the pursuit between them.

Kalin directs the labs that study fear, anxiety, and other negative emotions as they're activated in the primitive regions of the brain's limbic system. He began by observing the fear responses of monkeys in the lab. Young monkeys learn to deploy different fear responses for different situations: separated from their mothers, they'll coo for help; if a stranger enters the room, they'll freeze to avoid being noticed; if the stranger stares at them, they'll bark, show their teeth, and generally try to appear tough.

So what about the monkeys whose fear response is not appropriate, the ones that coo for help when they should be quiet or freeze up in the wrong situations? Their problems may stem from a cascade of stress hormones named after the corticotropin-releasing hormone, or CRH. Starting in the amygdala, a small emotional powerhouse deep in the brain, CRH triggers the production of adrenocorticotropic hormone, which triggers the release of cortisol. Cortisol is so caustic that it may scorch the brain during particularly stressful events, leaving permanent impairments in the emotional circuits. Kalin's lab found that very fearful monkeys have higher baseline levels of cortisol than other monkeys. The fact that their mothers have similarly high levels, and similarly anxious behavior, suggests that excessive fearfulness may be inherited as well as learned.

Now labs at the HealthEmotions Research Institute are picking apart the CRH system. Reseachers are stressing rats, slicing their brains, and looking for areas where the CRH system is actuated. They're unraveling the hormone's genetic code and studying how strong, steady pulses of CRH might cause the proteins that receive it into the cell to permanently retract. (This might be the same mechanism by which traumatic stress causes permanent disorders in people.)

Meanwhile, they're injecting drugs that block CRH into different parts of the limbic system of rats to see if treated rats are less likely to cower in the dark parts of the maze. By injecting the drug, they may be blocking anxiety before it occurs. So by studying how anxiety is activated, Kalin and his associates may have actually found a way to deactivate it. But is a rat that experiences less stress one with a positive affective style? Not necessarily. Positive affective style is really the ability to turn negative emotions off after they've started, and that's associated with the other end of the system.

The prefrontal cortex is the layer of gray matter that covers the foremost part of the brain's sophisticated frontal lobe--the lobe associated with cognition and intelligence. Davidson first suspected the prefrontal cortex had some role in regulating emotion when he read a study observing that patients with lesions on the left side of their prefrontal cortices tended to be melancholy and depressed, while those with damage on the right were cheerier, even manic.

He decided to test the theory, and assembled 90 right-handed subjects. Covering their scalps with a net of electrodes so that he could compare patterns of electrical activity underneath, he tested to see which side of each subject's prefrontal cortex seemed to be more active. Then he had each take a questionnaire designed to test the tendency to be active or inhibited in behavior, and he compared the results. Sure enough: people who answered yes to statements like, "When I want something, I go all out" were more left-lateral than those who saw themselves in statements like, "When I want something, I worry I'll make a mistake."

To figure out whether the people with more left-dominant prefrontal cortices were just oblivious to the darker possibilities in the world, Davidson devised a clever experiment based on the fact that most people blink when they're startled. If they're upset when they're startled, they blink longer.

To get an emotional reaction in the limited environment of the lab, Davidson used a set of photographs developed by University of Florida researcher Peter Lang. Some of the pictures were designed to evoke positive reactions (babies, puppies, nude people) and others to provoke negative ones (violent car wrecks and the like). Lang tested the pictures across hundreds of subjects, and the pictures were ranked for their evocative power.

Davidson showed his subjects the negative pictures, startling them with a loud noise immediately beforehand and then again while they were looking at each picture. Then he startled them several times afterward to see how quickly they recovered. Right-laterals continued to blink intensely after each picture was gone, and in fact seemed to get more upset in the moments after the picture was gone. Left-laterals reacted strongly while the picture was shown--in some cases more strongly than the right-laterals--but they mastered their startled blinking more rapidly.

At the April symposium, Davidson listed a host of other positive qualities his left-lateral subjects enjoy--everything from positive affect while they're dreaming to greater ability to anticipate positive incentives. When he was through, there was a question from the audience, someone wanting to know at what point all this positive affect becomes maladaptive. A little later someone else asked the same thing, citing studies that link right-lateral activity to empathy. Maybe these audience members were wondering how much they'd enjoy being surrounded by people who jump out of bed in the morning and go all out. Or maybe they weren't sure they liked the idea of an absolute standard of emotional health.

Davidson reminded his audience that he doesn't claim to have discovered an absolute standard. And he reminded them again that it's not that his left-laterals didn't feel negative emotion; in some cases they felt it more deeply, but appropriately. Then they rapidly recovered.

Of course, we could all stand to feel negative emotions more appropriately and recover more quickly. And if we could identify a standard, we would probably choose to move toward it; in fact, we adjust our emotional behavior in response to our experience every day. Davidson confirmed this theory with another experiment using disturbing pictures and startling sounds. This time the lab instructed each subject to either enhance, suppress, or maintain the emotion inspired by the card. The results? Subjects were able to suppress their emotional blinking just by deciding to, though of course the left-laterals did it better.

But to what extent can we rewire the circuits themselves? Doctors at medical centers around the world are already treating depressed patients with magnets to see if stimulating their left cortices will help alleviate the depression. And at Northwestern University, Dr. Peter Rosenfeld has developed a biofeedback system that may help train patients to swing their prefrontal activity toward the left.

Meanwhile, Davidson has been exploring the powers of meditation. In a study with Jon Kabat-Zinn at the University of Massachusetts Medical School, researchers trained executives of fast-paced biotech companies in meditation techniques. Davidson has also been working on experiments involving Tibetan monks. But he isn't talking about the results yet, since he's just submitted a paper for publication.

And Kalin has suggested that behavioral training could teach extremely inhibited people to regulate mood-altering neurotransmitter systems. "One of the best ways to get over a fear is to get that person in a scary situation so their bodies get used to it and they realize that what's really scaring them is their physical response," he says. (It might be that such exposure works by toning down the CRH system, "but that's a big 'might,'" he adds.)

Then there are drugs. There is tentative evidence that some antidepressants make patients more left-lateral, though it's unclear how long the effects last. Specifically, Davidson's left-lateral subjects sound a little like the patients taking selective serotonin reuptake inhibitors, or SSRIs, in Peter Kramer's Listening to Prozac. On Prozac, Kramer argues, his patients don't become terminally cheerful or oblivious to pain; they acquire a new ability to bounce back from adverse circumstances--a sort of emotional resilience.

Davidson is skeptical that what Kramer's patients and his own subjects experienced is the same thing, biologically speaking: "I don't know of a single study that has rigorously examined the effects of SSRIs on the rapidity of recovery following a negative event," he says. Though serotonin does reduce CRH levels: "We're thinking that's one of the ways it works, actually," says Kalin. Someday the HealthEmotions Research Institute's work on CRH blockers might translate into drugs that bypass the serotonin system, reducing anxiety and maybe avoiding the sexual dysfunction that is the major discouraging side effect of SSRIs.

Kramer was so impressed by the glorious effects of Prozac that it made him uneasy. There are certain ethical ambiguities that come with a drug that doesn't just make people more peppy or more relaxed, but makes them more lucid in their thinking, quicker to make decisions. He describes a patient who found that Prozac made her a more effective labor negotiator for her management-side bosses, leaving Kramer wondering if labor shouldn't have been offered Prozac, too. The ambiguity doesn't lie so much in the ethics and effects of taking a particular pill; it's more integral to emotional resilience itself.

When Davidson describes positive affective style, with its approach-oriented behavior and rapid recovery times, he describes what amounts to a fairly competitive personality. In fact, some scientists have found that anger, particularly anger directed at removing some obstacle to an individual's goal ("an important function of anger," Davidson adds), is associated with a similar pattern of brain activity as the positive affective style. And why shouldn't positive affective style be competitive, if emotions are, from the start, adaptive, the firing of each neuron trained on an evolutionary advantage? Still, if we take this as our model for behavior, aren't we just going to become an even more competitive society? Is positive affective style just aggressive personality?

Kalin is thoughtful. "Positive affective style or a resilient personality and so on, these terms are relatively new. So the idea that that kind of a person might be very outgoing or very approach oriented or very competitive is an interesting idea.

"My thought is that they don't necessarily go hand in hand. You can have a person who is very positive, adaptive, healthy emotionally who is not necessarily terribly competitive. You could also submit that if [a person is] very competitive [he's] not very healthy emotionally," he says. Very competitive people might have trouble getting along with others if they're not considered empathic, for instance.

Ultimately, he says, "the healthiest emotional style is to be able to experience a full range of emotions appropriately, but also to be able to turn them off when it's not appropriate." You can't argue with a definition based on what's appropriate. But as we learn to recover more rapidly, what is appropriate will certainly change. Meanwhile, Davidson says, "Undoubtedly as we begin to look more closely at these emotional states and characteristics we will discover other differences between an approach-oriented style that is tinged with anger and one that is more unequivocally positive."

So perhaps learning to be emotional athletes won't make us angrier, any more than cultivating our recovery times will make us all cutthroat competitors in an accelerating global economy or prompt us to give up our brooding novels for MTV. Whatever the evolutionary purpose that gave us emotions in the first place, it's our emotions that make us cling to things that aren't practical, that don't move the race forward, that aren't always advantageous to us as individuals. It's because of emotions that we don't want little monkeys with poor affective styles to suffer. And maybe we don't want to be people who jump out of bed in the morning, ready to go all out. But if everyone else is going to be that way, we might consider medication, biofeedback, or behavioral therapy.

Or we might turn to meditation. In a one-time experiment he says hasn't been published and isn't likely to be, Davidson flew a Buddhist monk in from Dharmsala to test his prefrontal cortex. When he placed the result on a scale with 175 of his regular subjects to see who was the most left-lateral, the gentle man from Dharmsala came out on the furthest extreme of the scale.

Art accompanying story in printed newspaper (not available in this archive): photos/J.B. Spector.

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