Science Watch

In 1933, Franklin Delano Roosevelt launched his presidency by telling Depression-weary Americans that "the only thing we have to fear is fear itself--nameless, unreasoning, unjustified terror which paralyzes needed efforts to convert retreat into advance." FDR's bold and immediate confrontation of fear helped him to galvanize a worried nation. Seventy years later, scientists may have shed light on how he did that.

New research into the extinction of learned fear shows that, in lab animals, facing fear upfront in closely spaced doses may work better than facing it slowly over time.

In the October 2003 issue of APA's Journal of Experimental Psychology: Animal Behavior Processes (Vol. 29, No. 4), researchers at the University of California, Los Angeles (UCLA) described their exploration of different approaches to extinguishing the fear of a conditioned stimulus. "Massing" the feared stimulus--delivering it in concentrated bursts, rather than pacing it with longer pauses in between--was surprisingly efficient, at least in mice. The findings may help clinicians to refine behavioral therapy, which--in most cases, research shows--successfully treats phobias, panic disorder, post-traumatic stress disorder and obsessive-compulsive disorder.

The findings underscore that conditioning and extinction are two distinct types of learning, not equal and opposite processes. Indeed, the University of Michigan's Steve Maren, PhD, says that the new paper reveals another aspect of extinction that differs from conditioning: "Namely, that it is improved by massed training--which is opposite of what happens with conditioning."

In conditioning, you learn to fear something neutral by its association with something unpleasant--a mild shock paired with a ringing bell. In extinction, you don't unlearn the fear; rather, you learn not to fear--a subtle but important distinction. In short, you don't erase; you override.

Understanding just how different the processes can be, along with the conditions that enhance extinction, such as the timing, intensity and context of exposure to the feared stimulus, may help psychologists to improve human therapies.

A matter of timing

In the study, Mark Barad, MD, PhD, the Tennenbaum Scholar in UCLA's Neuropsychiatric Institute, and neuroscience doctoral students Christopher Cain and Ashley Blouin taught mice to fear harmless white noise by associating it with a mild shock delivered through the floor of the experimental cage. The white noise thus became the conditioned stimulus, or CS. After a couple of trials, the mice "froze" for about 72 seconds, or 60 percent of the two minutes of white noise.

Freezing, one measure of fear among many, is defined as immobility except for the movement associated with breathing. Roosevelt, lacking the lingo, accurately termed it the suppression of action. This defensive response, rooted in the brain's amygdala and hippocampus, probably evolved as a way to deter predators.

After the initial conditioning, Barad and his colleagues separated the mice into three groups and measured how well they overcame their aversion to white noise when they heard it 20 times for two minutes each, without shocks--with intervals of six, 60 or 600 seconds between each presentation. Repetition of a conditioned stimulus has long been known to "extinguish" a fear by exposing animals, including humans, to that stimulus without the associated pain.

The only catch is that extinction can take a long time. Anxiety is like an unwanted houseguest: It breezes in quickly, without invitation, and is hard to kick out. Although current treatments have success rates ranging from about 60 percent for social phobia and panic disorder to 80 percent for obsessive-compulsive disorder and post-traumatic stress disorder, greater efficiency is always welcome to make therapy less aversive, more accessible and more cost-effective, experts say.

The UCLA study underscored one key to efficiency. In it, both short-term and long-term fear extinction were greater with "temporally massed" presentations of the stimulus. In other words, mice exposed to six seconds of silence between each of 20 intervals of white noise (the conditioned stimulus) stopped significant freezing after about 10 such bursts of noise--about 20 minutes' worth. The mice in the other two groups, whose pauses were 10 and 100 times longer, never really stopped freezing.

"This work shows us that in extinction, timing is important," says Gregory Quirk, PhD, of the physiology department at the Ponce School of Medicine in Puerto Rico. Quirk, who researches fear's roots in the brain, says the finding is interesting and unexpected, "because it disagrees with the long-standing notion that spaced training gives better learning than massed, or all-at-once, training. They show that a period of massed training is essential to kick-start extinction." Quirk adds that, unlike extinction, conditioning is easy without massed training.

The spacing of CS presentation is one key variable in extinction; others include the intensity of the CS, degree of fear experienced during its presentation, and when and where extinction happens. Yet scientists need to learn more about how these variables influence extinction, according to Michael Davis, PhD, who is the Robert W. Woodruff Professor of Psychiatry, Behavioral Sciences and Psychology at the Emory University School of Medicine and heads the Center for Behavioral Neuroscience.

From mice to men

Anxiety researchers remain mindful of the need to close the gap between lab studies and human therapy. Humans have more sophisticated cognition and language than do lab animals, observes psychologist Edna Foa, PhD, director of the Center for the treatment and Study of Anxiety at the University of Pennsylvania. On the one hand, this complexity enables cognitive therapy to work; on the other, it muddies the diagnostic waters.

Foa explains that, with people, therapists don't really know whether they are dealing with a conditioned stimulus. In the laboratory, researchers control the conditioning as well as the extinction--but when patients walk into therapy, it's not clear why they are anxious. Still, useful tools can come off the lab bench. "To the extent that these [rodent] studies have application," Foa says, "it has to do with the length and spacing between exposure sessions."

Those factors, of course, can weigh heavily on success. "We can't discount the results because they come from an animal study," says Mitchell Schare, PhD, a behavior therapist who directs the PhD program in combined clinical and school psychology at Hofstra University. "The basic laws of learning in animals can be extrapolated to humans."

Basic science also stands to gain. The UCLA results may help researchers to understand the underlying anatomy and physiology of extinction. Explains Barad, "We now believe that the amygdala orchestrates animal fear responses, through a variety of brain-stem and central-effector regions that control such things as increased startle, freezing with fear, increases of blood pressure and heart rate, and more." In addition, the hippocampus seems to store the complex information needed to learn to fear a place.

Quirk adds that the medial prefrontal cortex appears to be essential for remembering massed extinction training of the type in the UCLA study. Such insights into the anatomy of fear and its extinction could lead ultimately to the design of drugs that could enhance extinction without interfering with other learning.

Meanwhile, why are conditioning and extinction so different? Quirk suggests that extinction may need a kick-start to prevent the accidental learning of conditioning. He says, "If you just learned to be afraid of something life-threatening, you don't want an occasional safe encounter or two to obliterate your life-preserving fear responses." Plus, seeing the once-feared stimulus in new contexts could raise new doubts as to its safety. That could explain why extinction is somewhat fragile and can be disrupted by environmental changes, experts note. So, anxiety's tenacity may have sensible roots deep in our evolutionary past. But that's little comfort to people seeking relief.

By better understanding how extinction works in the lab and in the brain, Barad and his colleagues look in two hopeful directions: ever-more efficient behavior therapy and more effective and targeted drugs as adjuncts to therapy.

Maybe then, as Roosevelt hoped, there truly will be nothing to fear--not even fear itself.

Rachel Adelson is a writer in Raleigh, N.C.