Special Report: Brain Imaging Research
Volume 11, Number 5
NIDA Brain Imaging Research Links Cue-Induced Craving
to Structures Involved in Memory
By Neil Swan, NIDA NOTES Staff Writer
For years, drug abuse researchers have known that when addicts are exposed to drug-related cues,
such as the sight of drug paraphernalia or even a drug-using companion,
these stimuli can spark powerful drug craving. Using brain-imaging techniques,
scientists are literally seeing the changes that these environmental cues
trigger in the brain as they are taking place.
Researchers in NIDA's Division of Intramural Research (DIR) have recently
published brain imaging findings that show that cue-induced drug craving
is linked to distinct brain systems that are involved in memory. (For more
on using imaging to study craving, see NIDA-Supported Researchers
Use Brain Imaging to Deepen Understanding of Addiction)
"Drug craving is a central aspect of addiction and poses an obstacle
to treatment success for many individuals," says NIDA Director Dr.
Alan I. Leshner. "Twenty years of neuroscience research have brought
us to where we can actually see increases in specific brain activity that
are linked to the experience of craving. If we can understand the mechanisms
that cause craving in people addicted to cocaine or other drugs, more effective
treatment strategies can be developed that counteract craving."
||Dr. Steven Grant is lead
investigator on the craving study. The study continues with the latest PET
imaging scanner at the Center, probing how drug-related cues may disrupt
normal memory functions.
Using positron emission tomography (PET), Dr. Edythe D. London and her colleagues
at DIR's Addiction Research Center (ARC) in Baltimore produced brain images
showing that, in people who have used cocaine, cocaine-use cues spark increased
glucose metabolism in brain regions that are associated with memory. Increased
glucose metabolism indicates enhanced neural activity. By questioning the
volunteers whose brains were scanned, researchers correlated computer-screen
images with the cocaine users' responses about intensity of craving sensations.
To make the correlation, the brain images were examined for color changes
that are calibrated to show areas of increased glucose metabolism.
In the study, DIR researchers compared metabolic activity in the brains
of 13 volunteers who had used cocaine with activity in the brains of a control
group of 5 volunteers who had never used cocaine. The scans were taken after
the groups were exposed to both cocaine-related cues and neutral cues. The
cocaine-related stimuli consisted of observing drug paraphernalia and viewing
a videotape of cocaine users.
|Dr. Edythe D. London,
director of NIDA's new Brain Imaging Center, initiated the craving study
that has found links between cue-induced craving and the brain structures
involved in memory. A pharmacologist, she began brain imaging research in
1979 and came to DIR in 1981.
The cocaine-user group responded to the cocaine-related cues, but not to
the neutral cues, with increased glucose metabolism, which was visible in
the PET images and with their own reports that they were experiencing craving.
The greater the reports of craving, the greater the metabolic activity in
three key areas of the brain, the researchers found. The volunteers who
had never used cocaine reported no cocaine cue-induced craving and showed
no visual signs of cue-induced brain activity.
Among the brain regions activated by the cocaine cues were the dorsolateral
prefrontal cortex, amygdala, and cerebellum, which are all involved in aspects
of memory and learning. The amygdala has been linked to emotional aspects
of memory. The findings suggest that a neural network involving these brain
regions integrates the emotional and cognitive aspects of memory and reacts
to environmental cues and memories by triggering cocaine craving.
"These three areas show cue-induced activity changes that are highly
correlated with the behavioral measure, which is craving," says Dr.
London, director of the NIDA Brain Imaging Center and initiator of the study.
"Thus, we have identified brain circuits that may be targets for pharmacotherapy
or other treatments. We now have a practical system for testing potential
interventions. This system overcomes the limitations of an addict's own
subjective evaluations of craving sensations by using the PET scanner to
see, objectively, actual responses within the brain that correlate to craving."
Until now, the three brain regions identified by the researchers have been
associated with memory functions, but not with drug craving, says Dr. Steven
Grant, the study's lead investigator. These new findings support the hypothesis
that memory may be more critical to drug craving than is the traditional
concept of reinforcement. "The amygdala, which is involved in giving
memories emotional color, puts an emotional aspect on the cue-induced craving
sensations," he adds.
The current research into cue-induced craving continues with new PET scanning
equipment recently installed at the ARC. (See New Imaging Center Enhances NIDA's Brain Research)
Dr. London and her colleagues are using the new scanner to test whether
cue-induced craving impairs an addict's ability to perform simple daily
tasks. Preliminary findings confirm the hypothesis that cues can intrude
into working memory functions, producing distracting daydreams or cocaine-oriented
thoughts, says Dr. Grant. "Activation, by drug-related cues, of brain
regions that integrate the emotional and cognitive parts of memory could
contribute to one of the hallmarks of addiction-the excessive focus on activities
that lead to further drug use," Dr. London says.
PET scans conducted at NIDA's Brain Imaging Center reveal selective activation of brain circuits during cocaine craving. Scans from volunteers who experienced a high level
of cue-induced cocaine craving show activation of brain regions implicated
in several forms of memory. The scans at right show activation of the dorsolateral
prefrontal cortex (DL), which is important in short-term memory, and the
amygdala (AM), which is implicated in emotional influences on memory. When
these volunteers were exposed to neutral (non-drug-related) cues, this activation
was not seen (scans at left).
Grant, S.; London, E.D.; Newlin, D.B.; Villemagne, V.L.; Liu, X.; Contoreggi,
C.; Phillips, R.L.; Kimes, A.S.; and Margolin, A. Activation of memory circuits
during cue-elicited cocaine craving. Proceedings of the National Academy
of Sciences 93:12040-12045, 1996.
London, E.D., et al. Cocaine-induced reduction of glucose utilization in
human brain. Archives of General Psychiatry 47:567-574, 1990.
Stapleton, J.M., et al. Cerebral glucose utilization in polysubstance abuse.
Neuropsychopharmacology 13(1)21-31, 1995.
From NIDA NOTES, November/December, 1996
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