Impaired neural response to negative prediction errors in cocaine addiction

Abstract

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).