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Brain Studies Yield Clues to Desire and Motivation
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Brain Studies Yield Clues to Desire and Motivation
Recovering drug addicts who remain in their old neighborhoods often have trouble staying clean. Familiar sights spark the desire to return to old behaviors, they report. But how much exposure to visual stimuli is needed to trigger this kind of vulnerability?
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Anna Rose Childress, M.A. '76, Ph.D. '79 |
Not much, according to studies by Anna Rose Childress, M.A. '76, Ph.D. '79, a Research Associate Professor of Psychology in Psychiatry at the University of Pennsylvania School of Medicine. Childress, who uses noninvasive, in vivo neuroimaging to observe brain activity, found that a mere 33-millisecond flash of an image can set the brain's ancient reward circuitry in motion. "The cues are coming in under the radar, before you have a chance to mount a defense," she says.
There is strong evolutionary pressure for the brain to respond rapidly to reward signals, Childress notes, as this — in the case of food and sex — promotes species survival. The mesocorticolimbic dopamine ("GO!") system is critical for processing rewards and their signals, including drug reward cues. Frontal lobe ("STOP!") circuits are responsible for modulating the downstream "GO!" regions, for weighing the consequences of reward pursuit.
Animal studies have shown that "repeated exposure to stimulants may further erode your frontal lobe 'brakes,'" Childress says. "Our cocaine patients have a double whammy — they have a powerful learned response to drug cues, and they may be poorly equipped to modulate it."
A Career-Long Interest
"My graduate training at Bryn Mawr shaped my interest in, and my approach to, the topic of reward and its pursuit," Childress says. "Addictions turned out to be a natural place to see this process gone awry."
Childress's doctoral research at Bryn Mawr investigated the neurotransmitters involved in the brain's reward system by electrically stimulating the brains of rats. The animals "looked driven" as they pressed buttons, she says. "I was observing what looked like addictive behavior — before I had ever spoken with a cocaine-addicted person."
As a postdoctoral fellow at the University of Pennsylvania, Childress received clinical training in psychiatry. She first investigated a medication to blunt alcohol euphoria in social drinkers, and began studying opiate and cocaine addiction after joining the Penn faculty in 1982. From 1981 to 2006, she also had appointments at the VA Medical Center in Philadelphia, where she still sees a few longtime patients.
Craving and Arousal
Childress was inspired to test the response to "unseen" 33-millisecond drug cues after reading a pair of 1998 papers on the brain's response to fear cues presented outside awareness. She realized the techniques could be applied to cues for reward, including drug reward.
"When I saw the first article," she recalls, "It made my heart beat a little faster."
Childress was the first to document cue-induced cocaine craving and arousal. In her early work, she used short videos of (simulated) drug use shot with her own camcorder, later measuring skin temperature and other autonomic responses in her patients. As brain imaging became available, she pioneered the use of positron emission tomography (PET) and fMRI to map brain activity during craving induced by drug video cues.
Her recent imaging studies pushed the temporal envelope, using 33-millisecond drug and sexual cues presented by a technique that prevented their conscious recognition. The results offer "a peek into unconscious positive motivation," Childress says. "The notion of unconscious motivation has been around since Freud, but it has been hard to test." In Childress's studies, the brain activity in response to "unseen" cocaine cues strongly predicts future (two days later) affect to visible versions of the cues, underscoring the functional significance of the rapid brain response.
Childress's imaging work was featured in the recent HBO documentary, "Addiction." Her segment is "The Science of Relapse."
In her early clinical work, Childress developed a set of manualized behavioral strategies for "Coping with Cocaine Craving." The manual has been widely distributed by the National Institute on Drug Abuse; the tools were also modified for smoking cessation. "The behavioral tools make demands on the frontal 'STOP!' regions, encouraging patients to consider the consequences of acting on craving," she explains. "However, our patients have great trouble using these 'STOP!' tools when they're already in an intense craving state." For this reason, a medication that modulates the rapid response of the "GO!" system may be a critical partner for the behavioral strategies.
Solid Background
Childress lauds the rigorous experimental training she received at Bryn Mawr. "People within the department had a passion for their science," she recalls. "They lived and breathed it, and they fully expected that their students would, too. What was lasting to me was the excitement of science — to think about what it would mean across species and on different scales." It was thrilling, she says, "to see broad-brush thinkers do translational science — decades before the term was to become the trademark of the 'NIH Roadmap.'"
Bryn Mawr faculty members such as her doctoral thesis adviser Professor Larry Stein (now at the University of California at Irvine ), and Professor Earl Thomas, her master's adviser, Childress says, inspired within students a sense that the day's experimental result "could be really important; it could be helpful to people. It was a way of opening up your worldview … well beyond the walls of the laboratory."
Barbara Spector writes on science and technology as well as business topics. She is the editor-in-chief of Family Business magazine and former editor of The Scientist.