University of Southern California, USA.
University of Southern California, USA; University of California San Diego, USA.
Neuroimage Clin. 2019;21:101643. doi: 10.1016/j.nicl.2018.101643. Epub 2018 Dec 15.
Neuroadaptations caused by chronic methamphetamine (MA) use are likely major contributors to high relapse rate following treatment. Thus, focusing intervention efforts at pre-empting addiction in vulnerable populations, thereby preventing MA-use-induced neurological changes that make recovery so challenging, may prove more effective than targeting chronic users. One approach is studying casual/recreational users, not diagnosed with substance use disorder. This group may be at high risk for addiction due to their experience with MA. On the other hand, they may be resilient against addiction since they were able to maintain casual use over the years and not become addicted. Understanding their neuro-cognitive characteristics during decision-making and risk-taking would help solve this dilemma and, may help identify intervention strategies. Unfortunately, research on neuro-cognitive characteristics of casual MA users is currently lacking. In this work we begin to address this deficit. This study was part of a larger investigation of neural correlates of risky sexual decision-making in men who have sex with men. While undergoing functional magnetic resonance imaging, 31 casual MA users and 66 non-users performed the CUPS task, in which they decided to accept or refuse a series of mixed gambles. Convergent results from whole brain, region of interest and psychophysiological interaction (PPI) analyses are presented. Whole brain analysis identified an amygdala-striatal cluster with weaker activation in casual MA users compared to non-users during decision-making. Activity in that cluster inversely correlated with decisions to gamble: lower activation corresponded to higher risk taking. Using this cluster as a seed in PPI analyses, we identified a wide range of neural network differences between casual MA users and non-users. Parametric whole brain analyses identified clusters in the ventral striatum, posterior insula and precuneus where activations modulated by risk and reward were significantly weaker in casual MA users than in non-users. The striatal cluster identified in these analyses overlapped with the amygdala-striatal cluster. This work identified neural differences in casual MA users' reward processing and outcome learning systems which may underlie their increased real-world risk-taking. It suggests that while making decisions casual MA users focus primarily on potential gain unlike non-users who also take the riskiness of the choice into consideration.
慢性使用甲基苯丙胺（MA）引起的神经适应性变化可能是导致治疗后复发率高的主要原因。因此，将干预措施的重点放在预防易受成瘾影响的人群中，从而防止 MA 使用引起的神经变化，使康复变得如此具有挑战性，可能比针对慢性使用者更有效。一种方法是研究没有被诊断为物质使用障碍的偶然/娱乐性使用者。由于他们有 MA 的使用经验，这群人可能有很高的成瘾风险。另一方面，由于他们能够在多年来保持偶然使用而不沉迷，他们可能具有对成瘾的抵抗力。了解他们在决策和冒险过程中的神经认知特征将有助于解决这一困境，并可能有助于确定干预策略。不幸的是，目前缺乏关于偶然 MA 用户神经认知特征的研究。在这项工作中，我们开始解决这一不足。这项研究是对男男性行为者进行风险性行为决策的神经相关性进行的更大规模研究的一部分。在进行功能磁共振成像时，31 名偶然 MA 用户和 66 名非使用者进行了 CUPS 任务，他们决定接受或拒绝一系列混合赌博。呈现了来自全脑、感兴趣区域和心理生理交互（PPI）分析的一致结果。全脑分析确定了一个杏仁核-纹状体集群，在决策过程中，偶然 MA 用户的激活强度比非使用者弱。该集群中的活动与赌博决策呈负相关：较低的激活对应于更高的风险承担。在 PPI 分析中使用该集群作为种子，我们确定了偶然 MA 用户和非使用者之间的广泛神经网络差异。参数全脑分析确定了腹侧纹状体、后岛叶和楔前叶中的簇，在偶然 MA 用户中，风险和奖励调节的激活明显比非使用者弱。这些分析中确定的纹状体簇与杏仁核-纹状体簇重叠。这项工作确定了偶然 MA 用户的奖励处理和结果学习系统中的神经差异，这可能是他们在现实世界中增加风险承担的基础。它表明，在做出决策时，偶然 MA 用户主要关注潜在收益，而不像非使用者那样也考虑选择的风险。
