Cocaine Use Modulates Neural Prediction Error During Aversive Learning

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Virginia Tech

Cocaine use has contributed to 5 million individuals falling into the cycle of addiction. Prior research in cocaine dependence mainly focused on rewards. Losses also play a critical role in cocaine dependence as dependent individuals fail to avoid social, health, and economic losses even when they acknowledge them. However, dependent individuals are extremely adept at escaping negative states like withdrawal. To further understand whether cocaine use may contribute to dysfunctions in aversive learning, this paper uses fMRI and an aversive learning task to examine cocaine dependent individuals abstinent from cocaine use (C-) and using as usual (C+). Specifically of interest is the neural signal representing actual loss compared to the expected loss, better known as prediction error (δ), which individuals use to update future expectations. When abstinent (C-), dependent individuals exhibited higher positive prediction error (δ+) signal in their striatum than when they were using as usual. Furthermore, their striatal δ+ signal enhancements from drug abstinence were predicted by higher positive learning rate (α+) enhancements. However, no relationships were found between drug abstinence enhancements to negative learning rates (α±-) and negative prediction error (δ-) striatal signals. Abstinent (C-) individuals' striatal δ+ signal was predicted by longer drug use history, signifying possible relief learning adaptations with time. Lastly, craving measures, especially the desire to use cocaine and positive effects of cocaine, also positively correlated with C- individuals' striatal δ+ signal. This suggests possible relief learning adaptations in response to higher craving and withdrawal symptoms. Taken together, enhanced striatal δ+ signal when abstinent and adaptations in relief learning provide evidence in supporting dependent individuals' lack of aversive learning ability while using as usual and enhanced relief learning ability for the purpose of avoiding negative situations such as withdrawal, suggesting a neurocomputational mechanism that pushes the dependent individual to maintains dependence.

reinforcement learning, prediction error, cocaine, dopamine, fMRI