title: 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) who tested 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).
authors: Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors: Muhammad A
authors: MA
authors: Parvaz
authors: Center for Neural Science, New York University, New York, New York 10003.
authors: Anna B
authors: AB
authors: Konova
authors: Department of Psychology, Stony Brook University, Stony Brook, New York 11970, and.
authors: Greg H
authors: GH
authors: Proudfit
authors: Department of Psychology, Nevada State College, Henderson, Nevada 89002.
authors: Jonathan P
authors: JP
authors: Dunning
authors: Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors: Pias
authors: P
authors: Malaker
authors: Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors: Scott J
authors: SJ
authors: Moeller
authors: Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors: Tom
authors: T
authors: Maloney
authors: Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors: Nelly
authors: N
authors: Alia-Klein
authors: Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, rita.goldstein@mssm.edu.
authors: Rita Z
authors: RZ
authors: Goldstein
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D005071:Evoked Potentials; D030141:Feedback, Psychological; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012201:Reward
keywords: addiction; cocaine; event-related potentials; feedback negativity; reward-prediction error; self-medication
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