The young man sits in a small, quiet room, a computer terminal before him and earphones on his head. A net of 126 electrodes circles his scalp, wiring him up to a bank of computers in the room next door. The test is about to begin.
The first picture that flashes on the terminal is neutral: a city skyline. Then some negatives: an angry man being arrested, followed by a bloody, severed hand. Interspersed are the positives: a smiling man with a baby, a naked young couple enjoying each other's company.
Commonly used in the burgeoning field of affective neuroscience, these pictures are designed to stir happiness, sadness, contentment and disgust. Each electrode captures the electrical output of the small section of brain below, and together the electrodes show how the brain is activated by the emotions that the display provokes. Later, the people in this experiment will also be run through a new kind of magnetic resonance imaging (MRI) scanner that will record and plot their brain activity as they view more pictures of ice cream cones, skiers and maniacs.
Like scores of other tests going on at the Laboratory for Affective Neuroscience at the University of Wisconsin in Madison, the goal of this research is to learn more about the biology of emotions or, more specifically, about how the brain originates, processes and is changed by the emotions that mold human behavior. The research is still basic science, but the implications for future approaches to both mental illness and human happiness are considerable.
"We are trying to understand the brain mechanisms that support emotion--the actual circuitry in the brain that gives rise to these mental states," said Richard Davidson, a University of Wisconsin psychologist who has explored the field for almost two decades. "And we want to understand the mechanism by which these states get represented in the brain."
After decades of neglect and at times scorn, this scientific study of emotions is today among the hottest subjects in psychology, attracting millions in research dollars and increasingly wide attention. The National Institutes of Health, for instance, recently approved more than $10 million for the school as part of a five-year, national mind-body research effort.
Some of this turnabout is the result of new technologies that can provide images of how the brain is responding to emotional stimuli. Using positron emission tomography (PET) and the new generation of MRI scanners, researchers are locating the brain regions associated with different emotional states. They are also tracing the neural circuitry that the emotions travel and are moving toward an understanding of precisely how emotions are translated by the brain into behaviors and actions.
Left- and Right-Brain Emotions
Some of the new enthusiasm is the result of the iconoclastic Davidson, whose lab has done pioneering work in the scientific study of emotions--examining the brain functions of infants and the elderly, of people who are depressed and those who meditate.
Drawing on more than a decade of research, Davidson and his colleagues have made one of the more intriguing claims about the biology of human affect: that the two nearly identical hemispheres of the brain's prefrontal cortex (the outer layer of "gray matter") control and promote very different kinds of emotions. The related finding is that people vary greatly regarding which side of the brain is more active. This, in turn, has begun to shed light on why people respond to the same experience in such different ways.
For example, Davidson's research has found that the left side of prefrontal cortex, just behind the forehead, is the control center for positive, outward-reaching emotions related to setting and working toward goals. (Think of the visceral delight a toddler will show when running to a mother who has been away.) The corresponding right side of the prefrontal cortex is associated with inhibiting, withdrawing and more negative emotions. (Think of anxiety or feeling nervous about a strange sound.)
As Davidson explains it, this division into left and right is more than abstract theory. The lab also has pictures to support its findings from the PET and functional MRI scans, and it has brain wave measurements from electroencephalographs.
"We now know there are reliable differences in individuals regarding how their prefrontal cortex is activated when exposed to emotions like anger or pleasure," Davidson said. "We can see that some people will have more right-sided response to the emotion, some will have more left-sided response, and that both responses will remain relatively constant over time in those individuals."
In addition, Davidson has found that people with increased left-side activation generally report themselves to be happier, to have a more positive mood than people with increased right-side activity. The message is clear: How people experience life emotionally is reflected in, and to some degree determined by, which side of their brain is more active.
Davidson's research is still in its early stages and will need even better technology and years of research to bear fruit. But there is a pervasive optimism about where he and a small group of like-minded researchers in other labs are headed.
"This is a very difficult and long-term endeavor, but the payoff will be enormous," said Steven E. Hyman, director of the National Institute of Mental Health (NIMH) and a regular funder of Davidson's lab.
"Richie Davidson is one of a handful of people who is taking what we know from animal research about emotion and mood and, using the new technology, is applying that to the human condition," Hyman said. "If you know where in the brain there are real and important differences in people, it begins to point in very interesting ways toward new therapies."
Fear and Anxiety
Everyone can identify fear and happiness as emotions, but what exactly do people mean by the word "emotion"? And how can something as fleeting and hard to define as an emotion show up on pictures of the brain?
The question of what constitutes an emotion has been debated for decades, but was perhaps most cogently asked by the American philosopher and psychologist William James in the 1880s. Speaking of the fear experienced when running from a bear, he wondered which was the emotion: the conscious perception of the imminent threat or the body's reaction to it--the rush of adrenaline that quickened the heartbeat and got you running. James concluded that it was the physiological activity, but others now say they can detect emotional activity in the brain before any other bodily responses. So the chicken-or-egg debate continues.
There is a consensus, however, on what the word "emotion" does describe. An emotion is a short-term experience, as opposed to the more long-term "mood" or individual "temperament." In the world of affective neuroscience, emotion is today's weather while mood is the general climate in the area.
Because fear is among the most straightforward emotions and among the easiest to inspire, it has been the focus of much of the budding neuroscience of emotions. After years of research into the fear reactions of animals, scientists have been making significant headway into understanding how fear operates in humans, too.
They have found, for instance, that one small region deep in the human brain appears to be central to experiencing and processing fear. Called the amygdala because of its almond shape, it quickly receives all threatening and fearful information from the world and dispatches the neural--and later chemical-- messages that provoke the body to action. Using brain imaging, researchers have concluded there are two basic pathways to the amygdala--a quick, "down and dirty" circuit that stimulates immediate action and a slower, longer pathway to the brain's cortex, where a more thorough analysis of the threat can be made.
Amygdala-related research is going on across the country--at New York University, Emory University in Atlanta and Massachusetts General Hospital in Boston, among other places. A classic experiment involves fear conditioning and explores how the human brain (and most especially the amygdala) responds. In the study, people are told they may get a shock when a certain color is shown on a screen, but that they will not get the shock if any other color is shown. Invariably, when the color that allows for a shock appears, the amygdala of the person under study--as measured by an MRI--becomes highly activated. This happens whether a shock follows or not, indicating that it's fear of the shock that the amygdala is registering.
Davidson's lab has been involved in some of this work, but the lab's primary emphasis--and most unique contribution--has involved a broader range of emotions. While the amygdala may tell researchers a lot about why some people experience anxiety disorders and depression, it will probably tell less about the different ways some people are healthy and emotionally resilient. By examining the biology of both positive and negative affect, Davidson's lab is trying to uncover some of the secrets of happiness as well as emotional dysfunction.
According to Hyman of NIMH, work on understanding positive affect "is 10 years behind the work on fear and anxiety." That's no reflection on today's researchers, Hyman said, but rather a recognition that animal-based research into fear and negative emotions has been going on much longer and with greater intensity.
What's more, scientists have found it is much more difficult to inspire and measure positive emotions than negative emotions in the lab. As Davidson explains, an important part of emotion involves motion, yet it is virtually impossible to measure brain waves or glucose activation unless the subject is sitting still. In addition, positive emotions in adults tend to be more subtle than negative ones, and so are more difficult to identify and measure in the brain.
Nevertheless, a scientific structure for understanding the full range of emotions is being constructed. And as neuroscientists and psychologists increasingly see it, emotions are best understood not as discreet and specific feelings like sadness or happiness, anger or love, but as a continuum of responses.
Researchers, for example, have identified two poles that define human emotional states: One slides from pleasant to unpleasant, the other ranges from high activation or arousal to low activation or sleep. Embedded in the structure is the theory that emotions in their most basic form are about two behaviors--an inclination to approach and an inclination to withdraw.
This insight, which stems from years of work with animals and with brain-injured patients, has been expanded in the past decade with the advent of PET scans and the new functional MRIs that can capture brain activity over time. These technologies have added greatly to neuroscience, but they still only pick up levels of activation in the brain--the metabolism of glucose shown by PET and blood flow shown by MRI. They still don't tell with any specificity, for instance, what chemical is being activated by what neuron, or why.
Davidson's lab at the University of Wisconsin hopes to move past that stage with the help of a $3.5 million high field strength functional MRI device purchased for the school with the help of a $1.25 million grant from the W.M. Keck Foundation. Davidson said the new MRI will be the first of its kind dedicated primarily to the study of emotions.
"It's difficult to appreciate how incredibly rapidly changes have occurred in this area," he said. "On the basis of animal studies we had certain hypotheses about the human brain circuitry that underlie emotions, but we had no way to address them except through examining brain-damaged people. Now that's all changed and it seems like we're ready for some major steps forward."
Studying the biology of emotions in a lab takes constant innovation--both in selecting meaningful emotion-based responses, and then in learning how to measure them. The path can lead through some surprising neighborhoods.
For instance, the lab has tested the brain activity of 72 heavy cigarette smokers who were asked to not smoke for a full day. They were then outfitted with the 126-electrode net, shown a lighted cigarette and told they could smoke again in two minutes. During those two minutes of waiting, the left prefontal cortex, the area associated with positive goal attainment, lit up dramatically.
In a related test of 14 infants, the brain activity of the 10-month-olds was measured by electroencephalographs, and then the babies were briefly separated from their mothers. Most responded either by crying or by tentatively exploring their environments. In the babies who cried, the right prefrontal cortex (the center for more negative, withdrawn affect) was generally found to be most active. In the explorers, the left prefrontal cortex was more prominent. The conclusion: Brain circuitry can predict behavior and vice versa.
"By the end of the first year of life, specific patterns of brain activation reliably differ among infants," Davidson said. These patterns are associated with "dispositions that can become the building blocks for later adult personality as well as for vulnerability to psychopathology."
The possibility that brain circuitry affects or determines emotions has been discussed for decades by neurologists, who have reported a consistent emotional difference between patients with damage to their left prefrontal cortex and those wounded on the right. Left-side damage was closely associated with unusually deep depressions, while right-side injuries tended to produce unexplained euphoria or indifference to neurological damage.
Much of Davidson's work has involved efforts to explore this phenomenon further.
Another method used to measure emotions takes advantage of the fact that human beings, with the exception of some sociopaths, blink when exposed to a loud noise. Davidson and others have found that the size and duration of the blink will be affected by the emotional state of the person hearing the noise. Prior research found similar reactions in animals.
And so university students are regularly hooked up via electrodes surrounding one eye to computers that measure their blinks. A 95-decibel burst of white noise accompanies or follows the showing of emotionally charged pictures from the collection of University of Florida researcher Peter Lang. He has assembled a selection of more than 700 standardized emotion-rousing images that make up the widely-used International Affective Picture System. After a frightening or disgusting picture, a person will blink harder and longer; after a positive picture, the blink will be reduced.
This research examines individual differences in blink intensity and duration. One of Davidson's key findings is that the regulation of emotions--how they are turned off and on--is central to understanding the biology of emotions. People who have particularly long blink reactions, the lab has found, are having difficulty activating brain circuitry that turns their negative emotions off. And that difficulty, Davidson believes, may be associated with depression and other mental illnesses.
Many of the students in these "startle probe" experiments are later run through the fMRI--affectionately called the magnet--to check whether they are strongly right- or left-sided in their prefrontal cortex brain activations. Indeed, most people with long startles, Davidson said, show increased right-sided (negative) activation as their baseline.
The lab is also using the startle probe to understand positive emotions. People in one experiment are shown a computer monitor that spins numbers like a slot machine and are told they will win money if the numbers come up a certain way. White noise goes off before and after the numbers stop, and the startle magnitude is measured. The goal is to record the brain circuitry associated with the anticipation of a reward, and then with the winning of the reward. How intense is the response and where is it located in the prefrontal cortex?
Davidson says that his lab has been exploring this "pre-goal-attainment positive affect" because it appears to be an important part of emotional life.
"The ability to keep a goal in mind when it isn't physically present is one of the things we've found to be associated with the left prefrontal cortex and with the positive emotion that it supports," Davidson said. "We've found that a certain class of depressed people have a pervasive inability to experience this pre-goal-attainment positive emotion, and we think that explains many of their symptoms."
The lab has also begun exploring the unusual emotional resilience shown by some Wisconsin volunteers in a long-term study that began in 1957. This selected group of 28 people are now widows and widowers in their late fifties, who have suffered over the years yet showed up as emotionally balanced and positive on psychological screenings. Davidson and his colleagues will be giving them brain scans over the next three years to see if their brain circuitry shows consistent patterns. Some early results of related tests are expected next year.
"Emotional health may be most closely associated with the capacity to feel emotions deeply but appropriately, and then rapidly recover," Davidson said. In terms of brain biology, emotional balance appears to depend on the proper activation along a network of neural circuits. That network, Davidson said, connects both hemispheres of the prefrontal cortex with the amygdala and with the hippocampus, a chili-shaped region deep in the brain.
The hippocampus is believed to be associated with context-setting--the ability to keep appropriately aware of the dangers present, or not present, around you. The lab is exploring the hypothesis that a shrinkage of the hippocampus, due to overexposure to the stress hormone cortisol, is directly involved in the onset of post traumatic stress disorder (PTSD)--a condition where normal context-setting is missing.
Using brain imaging, the lab is measuring the hippocampus in PTSD patients to determine how undersized they are, and to test whether that brain region activates differently in PTSD patients.
By tracking these neural pathways, Davidson and his colleagues are hoping to ultimately understand and map the emotional workings of the brain, just as researchers have been able to graph the circulatory or endocrine systems. If they succeed, they will have an objective, brain-based understanding of aspects of human nature--like temperment, personality, mood--that have so far eluded scientific analysis.
This information could lead to new understandings of how personalities and moods are related to physical health and well-being. What's more, this knowledge could some day allow therapists to diagnose and treat psychiatric disorders based on what emotional circuitry was found to be malfunctioning--a possibility that comes with both promise for sufferers and some ethical questions for society.
The neuroscience of emotions is a new discipline. While Davidson's research has been generally well received, questions remain about the value of some studies on feelings, and also about the use of brain imaging as a way to "read" brain functions and emotional states. Earlier this year, for instance, Hyman of NIMH was quoted as saying that some of the brain imaging he has reviewed reminds him of phrenology--a pseudoscience of the 19th century that sought to understand emotions by measuring the contours of a person's skull.
In a recent interview, Hyman repeated his concerns about the indiscriminate use of brain imaging technology, saying that measuring when and where the brain lights up has little inherent value. Only when the research builds a scientific framework for explaining something important--like Davidson's investigations of how emotions originate in the brain--does the technology advance science, he said.
"My only regret now is there aren't a lot more groups doing this basic research," Hyman said. "In terms of human health and happiness, there is little that is more important. This is hard stuff, but people are making progress."
In the Brain, Emotions Take Sides
Imaging studies show that the brain's left prefrontal cortex is more active when positive, expansive emotions are experienced. By contrast, the right prefrontal cortex is associated more with negative and inhibiting feelings.
Individuals tend to activate one side of the prefrontal cortex more than the other in response to daily events. This finding leads researchers to believe that basic levels of emotional well-being -- who tends to be happy and who is prone to depression -- reflect which brain hemisphere is more active. People whose left prefrontal cortex is dominant are more likely to be optimistic and extroverted. Those whose right prefrontal cortex is more active tend to be more pessimistic and withdrawn.
Scientists first noticed this emotional division in brain-damaged patients, who were prone to euphoria or depression depending on which side of their brain was injured.
Source: Society for Neuroscience
Mysteries of the Brain
This year marks the end of the "Decade of the Brain," proclaimed by President Bush in 1990. With more powerful imaging devices and new genetic information, scientists are exploring the secrets of the organ that makes humans unique. Out of this research has come a much more dynamic and flexible view of the brain. This is
the second of several articles in Health about mysteries of the brain.
HEALTH TALK ONLINE
Got a question about the brain and emotions? Join us today at 3:30 p.m. for a discussion of this topic on The Washington Post's Internet edition at www.washingtonpost.com/liveonline. Our guest is University of Wisconsin psychologist Richard Davidson. Send in your comments and questions.
CAPTION: Mapping Emotions (This graphic was not available)