Cover Story

More than 10 million adults in the United States suffer from some sort of phobia, according to the National Institute of Mental Health. These exaggerated fears--whether of spiders, needles (see page 100), snakes, heights, social situations (see page 92) or even public spaces (see page 94)--can become so all-consuming that they interfere with daily life.

The good news is that over the past several decades, psychologists and other researchers have developed some effective behavioral and pharmacological treatments for phobia, as well as technological interventions.

Now researchers are taking the next step, says psychologist and phobia researcher Arne Öhman, PhD, of the clinical neuroscience department at the Karolinska Institute in Sweden. They are using neuroimaging techniques like positron-emission tomography (PET) and functional magnetic resonance imaging (fMRI) to understand the brain circuitry that underlies phobia and what happens in the brain during treatment.

They're finding that the amygdala--a small, almond-shaped structure in the middle of the brain's temporal lobes--is a key player, and that malfunctions of the amygdala and associated brain structures may give rise to many phobias. Still, researchers have yet to work out the details of how this happens.

"As soon as we know more about what is happening in the brain, then we can fine-tune treatment," Öhman says.

The biology of fear

All phobias are anxiety disorders, lumped in the same class as post-traumatic stress disorder and panic disorder, among others. And anxiety disorders are, fundamentally, based on fear.

"What we know about the neurocircuitry and brain basis of fear originally comes from animal research," says psychiatrist Scott Rauch, MD, of Harvard Medical School. Indeed, more than 30 years of research has examined the neurological underpinnings of fear in laboratory rats.

The workhorse paradigm has been the fear conditioning/fear extinction model, Rauch explains. In this model, researchers condition rats to fear a neutral stimulus, like a particular tone, by pairing it with something aversive, like an electric shock. Then, later, the researchers can "extinguish" this fear by repeatedly playing the tone without the accompanying shock. The researchers can use electrodes to record electrophysiological activity in the rats' brains during the fear conditioning or extinction process.

"Using this paradigm, in the past 25 years we've been able to pinpoint pretty precisely where to look for fear in the brain," says New York University psychologist Joseph LeDoux, PhD, a pioneer of this type of research.

What they've pinpointed is the amygdala. LeDoux and others have found that there is a double pathway leading to and from the amygdala. One path leads directly from a frightening sensory stimulus--like the sight of a snake or the sound of a loud crash--to the amygdala in just a few thousandths of a second. A second, slower pathway travels first to the higher cortex before reaching the amygdala.

"The shorter pathway is fast but imprecise," LeDoux explains. "If a bomb goes off, you might not quickly be able to evaluate any of the perceptual qualities of the sound, but the intensity is enough to trigger the amygdala. If you knew a lot about bombs, then through the cortex pathway you could evaluate the danger, but it will take longer."

The fast pathway, then, is the brain's early warning system, explains LeDoux, and leads to physical manifestations of fear like a racing heart and sweaty palms. The second pathway can override the first, and either lead to conscious feelings of fear or no fear. Studies like these have led researchers to believe that phobias and other anxiety disorders are caused by some type of dysfunction in the amygdala and related brain areas.

Moving to humans

The detail and scale of what researchers have learned from animal experiments is extraordinary, according to Rauch. "But the disadvantage is that you have to extrapolate from what you've learned to humans, and particularly to humans with anxiety disorders," he says.

So about a decade ago, researchers began to try to examine the analogous processes in people, using brain-imaging technology such as PET and fMRI.

What they've found has already led to a greater understanding of many anxiety disorders, particularly obsessive-compulsive disorder and post-traumatic stress disorder.

Fewer studies have focused on phobias, Rauch says: "The data there are a little less developed, and the results less cohesive." The first studies, from the early and mid 1990s, were symptom-provocation studies: Researchers would show, say, a snake-phobic person a snake or a picture of a snake, and then use PET scans to examine the brain's reaction.

"Heuristically, it was appealing to believe that these phobic disorders would be related to abnormalities in the fast-track through the amygdala," Rauch says. But in fact the earliest studies--like a 1995 study by Rauch in the Archives of General Psychiatry (Vol. 52, No. 1, pages 20-28)--didn't find any evidence of amygdala activation, although some cortical areas that communicate with the amygdala were active.

As measurement and experimental techniques have developed over the past decade, though, the findings have developed as well. For example, fMRI works more quickly than do PET scans, so researchers can examine the brain's reaction to stimuli in a narrower time scale, Rauch explains. In a 2003 study from Neuroscience Letters (Vol. 348, No. 1, pages 29-32), for example, psychologist Wolfgang Miltner, PhD, and his colleagues at Friedrich Schiller University in Germany used fMRI to examine spider phobics as they viewed pictures of spiders, snakes and mushrooms. This time the researchers found that the amygdala was more active in the spider phobics than in control participants.

Other researchers have found that "masking" the phobia stimulus, so that participants see it but are not consciously aware of it, produces interesting results. In a 2004 study in Emotion (Vol. 4, No. 4, pages 340-353), Öhman and his colleagues flashed 16 snake and spider phobics with pictures of a snake and a spider, each followed by a neutral picture. The presentation was so fast that the participants were not consciously aware that they had seen the snake or spider. Next, the researchers waited long enough for the participants to consciously register the feared stimuli before presenting the neutral ones.

The researchers found that when the timing did not allow conscious awareness, the amygdala responded to both the phobic and fear-relevant stimuli (fear-relevant stimuli were snake pictures for spider phobics, and vice versa). But when the timing did allow awareness, the amygdala responded only to the phobic stimuli. This suggests, Öhman says, that the amygdala responds immediately to anything that might be threatening, but that with more time to process other areas of the brain suppress the amygdala's initial response.

Finally, some researchers have begun to look particularly at what happens in the brain during and after phobia treatment. Psychologists Tomas Furmark, PhD, Mats Fredrikson, PhD, and their colleagues at Uppsala University in Sweden used PET scans to examine the brain activity of 18 people with social phobia as the people spoke in front of a group. Then, one-third of the participants received nine weeks of cognitive-behavioral therapy, one-third received the selective serotonin reuptake inhibitor Citalopram and one-third received no treatment. The researchers tested the patients again, using the same public speaking task, at nine weeks and again after one year. They found that the activation in the amygdala and related cortical areas at nine weeks could predict which people's symptoms would improve after one year.

Though all of these findings are shaping researchers' understanding of the parts of the brain that give rise to phobia, the picture is far from complete.

"This is a critical area of research for the future," says Rauch.

Further Reading

  • Rauch, S.L., Shin, L.M., & Wright, C.I. (2003). Neuroimaging studies of amygdala function in anxiety disorders. Annals of the New York Academy of Sciences, 985, 389-410.

  • LeDoux, J. (2003). The emotional brain, fear, and the amygdala. Cellular and Molecular Neurobiology, 23(4-5), 727-738.