Researchers at the National Institute on Alcohol Abuse and Alcoholism have found that anticipation of increasing monetary rewards selectively activates the human nucleus accumbens of the ventral striatum. Since this brain region is implicated in animal studies of alcohol and drug self-administration, the research may help lead to methods for understanding the biological basis of alcohol and drug craving in humans.

Researchers in the laboratory of Daniel Hommer, M.D., measured changes in blood oxygen level dependent contrast in a functional magnetic resonance (FMRI) scanner in order to track changes in brain activity that occurred while eight volunteers participated in a videogame task involving real money. In this monetary incentive delay (MID) task, participants saw cues that indicated that they might win or lose money, waited for a variable anticipatory delay period, then tried to either win or avoid losing money by pressing a button in response to a rapidly presented target. The researchers examined the response of the nucleus accumbens during anticipation of different amounts of potential rewards (i.e., gains of $0.20, $1.00, and $5.00) or punishments (i.e., losses of $0.20, $1.00, and $5.00). They found that nucleus accumbens activity increased as volunteers anticipated increasing monetary rewards but not punishments. Another nearby brain region, the medial caudate, showed increased activity not only during anticipation of increasing rewards but also during anticipation of increasing punishments.

After playing the game, volunteers rated their reactions to the various cues. Increasing reward cues evoked increasing self-rated happiness as well as nucleus accumbens activity. At the $5.00 level, volunteers who were happiest to see the reward cue also showed more anticipatory activation in the nucleus accumbens. "Our findings provide the first hint that activity in the nucleus accumbens may be related to the types of positive feelings that occur when people expect natural rewards," said principal investigator Brian Knutson, Ph.D. "This is an important step towards demonstrating that the brain circuitry underlying positive and negative feelings may not be the same in humans."

Using a different FMRI task and analytic method, another group of researchers at Harvard funded by the National Institute on Drug Abuse recently observed activation of the nucleus accumbens and other brain areas as volunteers anticipated a single level of monetary gain or loss, as documented in the May issue of Neuron. By varying the amount of anticipated reward, the NIAAA researchers extended this work to show that the nucleus accumbens responds proportionally to increasing rewards but not punishments. In addition, the NIAAA study links reward-related feelings to nucleus accumbens function.

"Today's report emphasizes the specific importance of the nucleus accumbens in the anticipation of reward and adds valuable new information toward understanding the role of reward in addiction," said NIAAA Director Enoch Gordis, M.D. "Since craving is a major problem that many alcoholics face on an ongoing basis, NIAAA is committed to understanding brain mechanisms related to craving and developing interventions that can help alcoholics to withstand the urge to drink."

In a given year, about 8 million adult Americans meet clinical diagnostic criteria for alcohol dependence (alcoholism) and about 6 million meet clinical criteria for alcohol abuse. At some time during their lives, 13 percent of Americans experience alcoholism and about 6 percent experience alcohol abuse.

The study was conducted at the NIAAA Division of Intramural Clinical and Biological Research, Laboratory of Clinical Studies, Section of Brain Electrophysiology and Imaging and will appear in the August 15 issue of the Journal of Neuroscience (Volume 21, RC159, pp. 1-5, 2001). The research report is available online at http://www.jneurosci.org/cgi/content/full/20015472 after midnight on August 3.

A description of work underway in the Division of Intramural Clinical and Biological Research and additional alcohol research information are available at http://www.niaaa.nih.gov. For interviews with Dr. Knutson, please telephone the NIAAA Press Office (301/443-0469).