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In people with a cocaine addiction, brain circuits responsible for predicting emotional loss become impaired, according to new research conducted at the Icahn School of Medicine at Mount Sinai in New York. That is one reason why many continue to use the drug even after facing devastating consequences such as imprisonment or the loss of a relationship

The researchers focused on the difference between a likely reward (or loss) and its relationship to a given behavior and a person’s ability to predict that outcome, a measurement known as Reward Prediction Error, or RPE.

It is believed that RPE signaling drives learning in humans and, therefore, guides future behavior. After learning from an experience, we can usually change our behavior without having to go through the whole experience again, and thus maximize rewards and avert expected losses.

Past research has shown that prediction of actual reward or loss is managed by shifting levels of the nerve signaling chemical dopamine produced by nerve cells in the midbrain, where changes in dopamine levels accompany unexpected gains and losses.

For the new study, researchers recorded the brain activity of 50 cocaine users and 25 healthy controls through an EEG scan, a test that detects electrical activity in the brain, while participants played a gambling game.

Each player was asked to predict whether or not they would win or lose money at each trial. The cocaine users showed impaired loss prediction, meaning their brains failed to trigger RPE signals in response to worse-than-expected outcomes compared to the healthy controls.

The results offer insights into why addicted individuals often fail to learn from negative outcomes even after encountering several setbacks.

“We found that people who were addicted to cocaine have impaired loss prediction signaling in the brain,” said Muhammad Parvaz, Ph.D., assistant professor of psychiatry at the Icahn School and lead author of the study.

“This study shows that individuals with substance use disorder have difficulty computing the difference between expected versus unexpected outcomes, which is critical for learning and future decision making. This impairment might underlie disadvantageous decision making in these individuals.”

Next, the researchers evaluated the individual differences among the 50 cocaine users. Half of the subjects had used cocaine within 72 hours of the study and the other half had abstained for at least 72 hours.

Those who had used cocaine within 72 hours showed higher electrical activity associated with the brain’s reward circuit when they had an unpredicted compared to a predicted win, a pattern similar to the 25 healthy controls. Those who had abstained for at least 72 hours did not show this higher activity in response to an unpredicted win.

These findings support the hypothesis that in addiction the drug is needed to normalize a certain brain function, which in this case is RPE signaling of better-than-expected outcomes.

“This is the first time a study has targeted the prediction of both gains and losses in drug addiction, showing that deficits in prediction error signaling in cocaine addicted individuals are modulated by recent cocaine use,” said principal investigator Rita Goldstein, Ph.D., professor of psychiatry and neuroscience.

“Direction of results supports the self-medication hypothesis in drug addiction whereby drug self-administration improves response to reward in drug-addicted individuals.

“The reductions in prediction of loss across all cocaine addicted individuals included in this study are also of great interest; they could become important markers that can be used to predict susceptibility for addiction or relapse or to develop targeted interventions to improve outcome in this devastating, chronically relapsing disorder.”

The study is published in The Journal of Neuroscience.

Source: Mount Sinai Medical Center

Cocaine photo available from Shutterstock