Neuroscientist Richard J. Davidson, PhD, Vilas Professor of Psychology and Psychiatry at the University of Wisconsin, directs the Brain Imaging and Behavior Laboratory at the University's Health Emotions Research Institute.(2,3,12)

Q. How is studying the brain going to help us understand how our emotions manage to "get under the skin" and affect our health?

A. Many reports have linked emotional factors and health status, but precious little work has been dedicated to understanding the brain mechanisms by which emotions influence health. Once you begin to ask that question, you have to refocus and redirect your efforts. Paper and pencil questionnaires measuring optimism or pessimism, for example, won't take you where you want to go because they aren't clearly tied to brain mechanisms.

So, you look at brain circuitry and its outputs. From there you try to get a handle on the mechanisms by which those outputs actually influence systemic bodily processes, like endocrine, immune, and autonomic functions, which play a role in modulating health. And that's where we look for individual differences in personality traits, attitudes, and moods.

Q. What have you found?

A. Importantly, we've discovered that people differ in the activation of their left and right prefrontal lobes of the cortex. Some people walk around on a daily basis with the left prefrontal region more activated. Others walk around with their right prefrontal regions more activated. The differences are consistent over time, and they correspond with certain personality traits, attitudes, and emotions.

Q. What types of traits and emotions?

A. We discovered that the people with a more active left prefrontal region report themselves to be more cheerful, more enthusiastic, more eager and alert, more engaged in life. They also show more persistence in pursuing their desired goals, and rapid recovery from negative life events.

There's a whole cascade of physical differences that we've found as well, including differences in the immune systems. Two separate samples have shown that those with highly active left-frontol lobes have increased Natural Killer cell activity compared to individuals with right prefrontal activation. And they differ in their change in immune function in response to a stressful event. Persons with right-sided activation respond to a stressful event with a more pronounced decline in immune function.

The right-prefrontal people are also likely to have trouble turning off a negative emotion once it's turned on. They tend to be more vigilant for threats, hold on to negative life events and take longer to recover from them.

Q. Does the behavior cause the brain activity, or is it the location of the brain activity that directs the behavior?

A. We honestly don't know at this point. All we know is that right frontal activity is associated with being stuck in negative states or more responsive to negative events. Whether the right frontal activity actually causes that is another question.

Q. Are the differences wired into our genes?

A. Not necessarily. We believe genetic factors influence them, but we believe there will turn out to be important environmental factors also influencing them. Early in life it's possible to change which side is dominant. But later - we aren't sure yet. We're just beginning to look at that. Roughly from age 3 to 12, we see a great deal of change in frontal activity. We see early development as a likely time when there is important modulation of these brain circuits. But adults show stable patterns. If we test you today and then again a year from now, these parameters of brain function are likely to be very similar.

Q. Is there anything that can be done to modify this right side brain activity?

A. Since it is overactive in some people, we ought to start looking for ways to calm it down. One way might be through medications. Another way might be through retraining our right frontal brain by certain thought exercises, like meditation training. If you've got someone with a certain pattern of frontal activity and you really work on it, can you get him to shift? I don't think that's been well investigated yet. But it's clearly an important outcome of this type of work.

We already have a lead from monkeys: you give Valium, an anti-anxiety drug, to monkeys and it shifts their activity from right to left. That's a hint that these patterns can be modulated with currently available medicines. And we'll soon have data from the meditation study that we are running with Dr. Jon Kabat-Zinn. (See story below.)

Q. What is the long-term significance of this for people's health?

A. We are studying that using the Wisconsin Longitudinal Study, which began in 1957 with interviews of over 10,000 high school graduates. They have been interviewed periodically ever since, and now we are bringing about 100 of them into the laboratory to measure their brain activity and other functions. We've taken urine and blood samples and sleep data. We're even giving them influenza and Hepatitis A vaccinations to get readings of their immune response.

We're working with four different groups. Some have been exposed to major negative experiences, such as the death of a spouse or of an offspring, or living with a problem drinker, and others haven't; and among each of these there are some who have low levels of psychological well-being and others who have high levels. From our tests we should be able to determine if long-term exposure to stressful events and our reactions to those events can affect the frontal cortex functioning and health generally. We expect to have some answers by October.

Good Feelings...and Feeling Good

Positive emotions can lower the body's natural production of the major stress-related hormone, cortisol, according to William Lovallo, PhD, associate director of the MacArthur Foundation Research Network on Mind-Body Interactions and director of Behavioral Sciences Laboratories at the Veterans Administration Medical Center in Oklahoma City. (8)

Lovallo took baseline readings of each of 30 participants' cortisol levels during the calm and restful first day of a study.

On day two, each participant was told to deliver a speech on an emotional subject, such as being falsely charged with shoplifting. The speech was made before a video camera with white-coated laboratory workers looking on. Cortisol shot up to high stress levels.

On day three, the participants watched uplifting and humorous film clips: Bonnie Blair winning Olympic gold, Steve Martin in a comic routine, and a segment from the romantic animated movie, Lady and the Tramp. The feel-good day pushed cortisol below baseline levels.

"That's what surprised us," Lovallo says, "that we can actually dampen the entire system that generates stress responses in the brain by changing the emotional state of the individual to a positive state. That suggests there's something bi-directional about the system, that we can move it both up and down."

Lessons from the Wild

Among the 800 or so free-ranging rhesus monkeys that inhabit the island of Cayo Santiago off the east coast of Puerto Rico, the most dangerous time of life for the males may well be when they are at their healthiest.

The monkeys live in eight groups of about 100 each. When the males are adolescents between three and a half and five years old, they must leave their home group and move to another. It is, to say the least, a very stressful time in their lives.

Ned Kalin, MD, chair of the Department of Psychiatry at the University of Wisconsin School of Medicine and director of the Health Emotions Research Institute there, has been studying these monkeys in the wild for four years. (5,6,7)

"On Cayo Santiago, we're looking at the biology of the animals as well as their personalities and their fearfulness, from early in life," Kalin said. "We are following them year by year, getting blood samples for hormones, cerebro-spinal fluid for the neurotransmitters, measuring their left-right prefrontal lobe asymmetry, looking at their behavior, and then predicting how they are going to do in life."

What is most interesting is the 20 percent mortality during the transition year among the adolescent males who leave home, "even though it's a time when the animals are very robust physiologically."

"They are not dying because of terrible attacks on them or anything like that," Kalin says. "We believe the high mortality is due to a combination of increased stress from leaving home to face new animals, insinuating themselves into a new group, making friends, getting food last, after the others, and many other factors."

The overriding goal is to understand why some animals are resilient and others are not, Kalin says. A dramatic finding is that the mortality rate soars to 40 or 45 percent when only the sons of dominant mothers are considered. "These animals have been relatively well protected by their dominant mothers, and when they get to the chaotic outside world and have to fend for themselves, reading the situation and deciding whether or not to be aggressive, and how to handle many other problems, they probably just don't know what to do."

Kalin and his colleagues also work with rhesus monkeys at the University of Wisconsin, where he has selected those that react with extreme fear and anxiety in new or threatening situations.

"These are monkeys that typically will freeze when a person enters the room. They are hypervigilant. We believe they freeze because they are trying to remain inconspicuous in the face of a threat. Their reactions are akin to feelings we get when we walk into a crowd of new people and feel on the spot. Our impulse is to be quiet until we get comfortable. Shy people typically report that they feel like they're frozen or that they freeze when they approach crowds or new situations."

And the rhesus monkeys are much like people in another way that is especially significant for researchers: the "fearful" ones have right frontal activity just as do humans with anxious, pessimistic personality traits. Stressful monkeys also have higher than normal cortisol levels in nonstressful situations, suggesting that their level of physiological arousal is set higher.

The Long Arm of Pessimism

Do young adults who explain bad events pessimistically have more illness later in life?

They are clearly at risk for poor health in middle age, according to Christopher Peterson, PhD, of the University of Michigan, American Psychological Association President Martin E. P. Seligman, and their colleagues, who analyzed results of a California study of 1,500 pre-adolescent school-boys who had been followed since 1921.

Although all of the boys were generally healthy and successful as young adults, those who showed extreme pessimism in surveys in 1936 and 1940 turned out 25 percent more likely to die before reaching age 65.(9)

What You Can Do

The same stressful event can have profoundly different effects on different individuals, even widely different effects on the same individual in varying life circumstances.

More importantly, people who show relatively large physiological responses to the hassles and frustrations of everyday life are at significantly higher risk for disease. This is so even when their perceptions of the stress and their coping with it are comparable to those who show relatively muted stress responses, according to John Cacioppo, PhD, professor of psychology and a member of the Institute of Behavioral Medicine Research at Ohio State University. (1)

How can "high reactors" change to "low reactors" and improve their health outlook? Suggestions by Cacioppo:

• Cultivate healthful behaviors - plenty of sleep, good nutrition and exercise. Without those, you may get irritable, reacting to things that shouldn't and wouldn't normally cause such reactions.
• Have a confidant, best friend, spouse, or someone else you can talk to honestly, to get support, feedback, and help putting events in perspective.
• Don't hold back emotional reactions. When psychiatrist David Spiegel of Stanford University worked with advanced breast cancer patients, he encouraged them to talk about how they felt. In a study of 86 women with metastatic breast cancer, participating in a support group "demonstrably improved both the patients' mood and their experience of pain." (ref. 14) More surprisingly, patients who confronted the worst in discussing the dying and death of other group members lived significantly longer than randomized control patients. (10,11)
• This does not mean go out and vent, says Cacioppo. "If I just vent, if I just rave, I'm being hostile. That's not productive. You want to be honest about the situation so you can deal with it effectively."

Scientists are trying to determine whether adults can actually change which frontal lobe of their brains - left or right - is most active by changing their behaviors.

In October, when scientists finish analyzing data, they should know whether and how an eight-week stress reduction course influenced brain wave activity and other biological patterns. That "may help us understand the mechanisms by which these types of training procedures may change the brain circuitry associated with emotional responding and also how it's linked with health," says neuroscientist Richard J. Davidson, PhD.

The study involves about 30 members of a high-tech firm who underwent extensive biological testing while participating in a mindfulness-based stress reduction course conducted by Dr. Jon Kabat-Zinn, a molecular biologist who developed the course 20 years ago at the Stress Reduction Clinic of the University of Massachusetts Medical Center. The program is now used by about 240 hospitals and medical centers in the United States and abroad as well as in schools, prisons, and multi-ethnic inner city neighborhood clinics. (4)

Kabat-Zinn says mindfulness meditation calls for "a huge lifestyle change, because what we are talking about is non-doing - how to be still. That is something most adult Westerners don't do much of."

Mindfulness is an ancient Buddhist meditation practice that Kabat-Zinn describes as moment-to-moment, non-judgmental awareness. "Most of the time the mind wants to be somewhere else, in the future, or in plans, or worry," he says. "All this may have little or nothing to do with the present reality. Gradually you train yourself to be more present in what's actually unfolding from moment to moment."

Kabat-Zinn is author of "Wherever You Go There You Are: Mindfulness Meditation in Everyday Life," 1994.

The Research

1. Cacioppo, JT (1998) "Somatic Responses to Psychological Stress: The Reactivity Hypothesis," Advances in Psychological Science, vol. 2.
2. Davidson, RJ (1998) "Affective Style and Affective Disorders: Perspectives from Affective Neuroscience," Cognition and Emotion, pp 307-30.
3. Davidson, RJ and Sutton, SK (1995) "Affective Neuroscience: the Emergence of a Discipline," Current Opinion in Neurobiology, pp 217-24.
4. Kabat-Zinn, J et al., (Fall 1998) "Influence of Mindfulness Meditation-Based Stress Reduction Intervention on Rates of Skin Clearing in Patients with Moderate to Severe Psoriasis undergoing Phototherapy (UVB) and Photochemotherapy (PUVA)," Psychosomatic Medicine.
5. Kalin, NH (May 1993) "The Neurobiology of Fear," Scientific American, pp. 95-101.
6. Kalin, NH et al. (1998) "Asymmetric Frontal Brain Activity, Cortisol, and Behavior Associated with Fearful Temperament in Rhesus Monkeys," Behavioral Neuroscience, pp. 286-92.
7. Kalin, NY et al. (1998) "Individual Differences in Freezing and Cortisol in Infant and Mother Rhesus Monkeys," Behavioral Neuroscience, pp. 251-4.
8. Lovallo, WR (1997) Stress and Health - Biological and Psychological Interactions, Sage Publications.
9. Peterson, C, Seligman, MEP et al. (March 1998) "Catastrophizing and Untimely Death," Psychological Science.
10. Spiegel, D, Bloom, JR, et al. (1981), "Group Support for Patients with Metastatic Cancer: A Randomized Outcome Study," Arch Gen Psychiatry, 38(5), pp. 527-33.
11. Spiegel, D, Bloom, JR, et al., (Oct. 14, 1989), "Effect of Psychosocial Treatment on Survival of Patients with Metastatic Breast Cancer," Lancet, pp. 888-891.
12. Sutton, SK and Davidson, RJ (May 1997) "Prefrontal Brain Asymmetry: A Biological Substrate of the Behavioral Approach and Inhibition Systems," Psychological Science, pp. 204-10.

This report was prepared with assistance from:

Academy of Behavioral Medicine Research
Academy of Psychosomatic Medicine
American Academy of Nursing
American College of Neuropsychopharmacology
American Psychiatric Association
American Psychological Association
American Psychological Association-Division 38
American Psychological Society
American Psychosomatic Society
American Sociological Association
American Society of Psychiatric Oncology
College on Problems of Drug Dependence
Institute for the Advancement of Social Work Research
International Psycho-Oncology Society
International Society for Traumatic Stress Studies
Society of Behavioral Medicine
Society for Developmental and Behavioral Pediatrics
Society for Public Health Education

The Center for the Advancement of Health promotes the science that explores the dynamic relationship among behaviors, emotions, biology, and social context, and works to integrate that knowledge into practical health care solutions. The Center is a nonprofit institute founded by the John D. and Catherine T. MacArthur Foundation and the Nathan Cummings Foundation, which continue to provide core funding.

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