Department of Psychology, Biological Psychology, University of Cologne, Cologne 50923, Germany
Department of Neurology, VA Northern California Healthcare System, San Francisco, CA 94121.
eNeuro. 2020 Jun 11;7(3). doi: 10.1523/ENEURO.0461-19.2020. Print 2020 May/Jun.
Gambling disorder is a behavioral addiction associated with impairments in value-based decision-making and cognitive control. These functions are thought to be regulated by dopamine within fronto-striatal circuits, but the role of altered dopamine neurotransmission in the etiology of gambling disorder remains controversial. Preliminary evidence suggests that increasing frontal dopamine tone might improve cognitive functioning in gambling disorder. We therefore examined whether increasing frontal dopamine tone via a single dose of the catechol--methyltransferase (COMT) inhibitor tolcapone would reduce risky choice in human gamblers ( = 14) in a randomized double-blind placebo-controlled crossover study. Data were analyzed using hierarchical Bayesian parameter estimation and a combined risky choice drift diffusion model (DDM). Model comparison revealed a nonlinear mapping from value differences to trial-wise drift rates, confirming recent findings. An increase in risk-taking under tolcapone versus placebo was about five times more likely, given the data, than a decrease [Bayes factor (BF) = 0.2]. Examination of drug effects on diffusion model parameters revealed that an increase in the value dependency of the drift rate under tolcapone was about thirteen times more likely than a decrease (BF = 0.073). In contrast, a reduction in the maximum drift rate under tolcapone was about seven times more likely than an increase (BF = 7.51). Results add to previous work on COMT inhibitors in behavioral addictions and to mounting evidence for the applicability of diffusion models in value-based decision-making. Future work should focus on individual genetic, clinical and cognitive factors that might account for heterogeneity in the effects of COMT inhibition.
赌博障碍是一种与基于价值的决策和认知控制受损相关的行为成瘾。这些功能被认为是由额-纹状体回路中的多巴胺调节的，但改变多巴胺神经传递在赌博障碍发病机制中的作用仍存在争议。初步证据表明，增加前额叶多巴胺能可能会改善赌博障碍患者的认知功能。因此，我们在一项随机双盲安慰剂对照交叉研究中，检查了单次给予儿茶酚-O-甲基转移酶（COMT）抑制剂托卡朋是否会增加前额叶多巴胺能，从而减少人类赌徒（ = 14）的风险选择。使用分层贝叶斯参数估计和联合风险选择漂移扩散模型（DDM）分析数据。模型比较显示，从价值差异到试验漂移率的非线性映射，证实了最近的发现。与安慰剂相比，托卡朋增加风险的可能性大约是降低风险的五倍[贝叶斯因子（BF） = 0.2]。检查药物对扩散模型参数的影响表明，托卡朋增加漂移率的价值依赖性的可能性大约是降低的十三倍（BF = 0.073）。相比之下，托卡朋降低最大漂移率的可能性大约是增加的七倍（BF = 7.51）。研究结果增加了 COMT 抑制剂在行为成瘾中的作用，以及扩散模型在基于价值的决策中的适用性的越来越多的证据。未来的工作应集中在可能解释 COMT 抑制作用异质性的个体遗传、临床和认知因素上。
