Impaired neural response to negative prediction errors in cocaine addiction.

Learning can be guided by unexpected success or failure, signaled via dopaminergic positive reward prediction error (+RPE) and negative reward-prediction error (-RPE) signals, respectively. Despite conflicting empirical evidence, RPE signaling is thought to be impaired in drug addiction. To resolve this outstanding question, we studied as a measure of RPE the feedback negativity (FN) that is sensitive to both reward and the violation of expectation. We examined FN in 25 healthy controls; 25 individuals with cocaine-use disorder (CUD) whotested positive for cocaine on the study day(CUD+), indicating cocaine use within the past 72 h; and in 25 individuals with CUD who tested negative for cocaine (CUD-). EEG was acquired while the participants performed a gambling task predicting whether they would win or lose money on each trial given three known win probabilities (25, 50, or 75%). FN was scored for the period in each trial when the actual outcome (win or loss) was revealed. A significant interaction between prediction, outcome, and group revealed that controls showed increased FN to unpredicted compared with predicted wins (i.e., intact + RPE) and decreased FN to unpredicted compared with predicted losses (i.e., intact - RPE). However, neither CUD subgroup showed FN modulation to loss (i.e., impaired - RPE), and unlike CUD + individuals, CUD - individuals also did not show FN modulation to win (i.e., impaired + RPE). Thus, using FN, the current study directly documents - RPE deficits in CUD individuals. The mechanisms underlying - RPE signaling impairments in addiction may contribute to the disadvantageous nature of excessive drug use, which can persist despite repeated unfavorable life experiences (e.g., frequent incarcerations).