Mount Sinai. US: Cocaine addicted individuals may continue their habit despite
unfavorable consequences like imprisonment or loss of relationships
because their brain circuits responsible for predicting emotional loss
are impaired, according to a study conducted at the Icahn School of
Medicine at Mount Sinai and published today in The Journal of Neuroscience.
The study focuses on the difference between a likely reward (or loss)
related to a given behavior and a person’s ability to predict that
outcome, a measurement known as Reward Prediction Error, or RPE. Such
RPE signaling is believed to drive learning in humans, which guides
future behavior. After learning from an experience, we can, in the best
case, change our behavior without having to go through it again, and
thus maximize rewards and avert expected losses. Past research has
determined 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.
The Mount Sinai study recorded the brain activity of 75 subjects (50
cocaine users and 25 healthy controls) using EEG, a test that detects
electrical activity in the brain, while subjects played a gambling game.
Each person had to predict whether or not they would win or lose money
on each trial.
Results showed that the group of the 50 cocaine users had impaired
loss prediction signaling, meaning they failed to trigger RPE signals in
response to worse-than-expected outcomes compared to the 25 healthy
people comprising the control group. The results offer insights into the
compromised ability of addicted individuals to learn from unfavorable
outcomes, potentially resulting in continued drug use and relapse, even
after encountering numerous losses.
“We found that people who were addicted to cocaine have impaired loss
prediction signaling in the brain,” said Muhammad Parvaz, PhD,
Assistant Professor of Psychiatry at the Icahn School of Medicine at
Mount Sinai and the 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 study looked at 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. The
cocaine addicted individuals with the more recent use had higher
electrical activity associated with the brain’s reward circuit when they
had an unpredicted compared to a predicted win, a pattern that was
similar to the 25 healthy controls. The cocaine users who had abstained
for at least 72 hours did not show this higher activity in response to
an unpredicted win. These findings are consistent with the hypothesis
that in addiction the drug is taken 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, PhD, Chief of
Neuropsychoimaging of Addiction and Related Conditions, Chief of the
Brain Imaging Center, and Professor of Psychiatry and Neuroscience at
the Icahn School of Medicine. “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.”
Collaborators include New York University, Stony Brook University and Nevada State College.
The study was supported by grants from the National Institute on Drug Abuse and the National Institute on Mental Health.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed
to providing distinguished care, conducting transformative research, and
advancing biomedical education. Structured around seven member hospital
campuses and a single medical school, the Health System has an
extensive ambulatory network and a range of inpatient and outpatient
services—from community‐based facilities to tertiary and quaternary
care.
The System includes approximately 6,600 primary and specialty care
physicians, 12‐minority‐owned free‐standing ambulatory surgery centers,
over 45 ambulatory practices throughout the five boroughs of New York
City, Westchester, and Long Island, as well as 31 affiliated community
health centers. Physicians are affiliated with the Icahn School of
Medicine at Mount Sinai, which is ranked among the top 20 medical
schools both in National Institutes of Health funding and by U.S. News
& World Report.
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