Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
Neuroimage Clin. 2024;44:103676. doi: 10.1016/j.nicl.2024.103676. Epub 2024 Sep 29.
Patients with stimulant use disorder (SUD) show impairments when making value-based choices that are associated with disruptions in neural processing across brain networks. Making optimal choices requires learning from outcomes to update knowledge and further optimise ongoing behaviour. The optimal functioning of neural systems that underpin the ability to make favourable choices is an essential component for life functioning, and successful recovery in patients with SUD. Therefore, we sought to investigate the neural processes that underpin value-based choices in SUD patients. We hypothesise that patients with SUD have reduced functional connectivity while making financial choices during a probabilistic reinforcement learning task.
We investigated connectivity associated with loss and reward value-based choices and their outcomes in patients with SUD and healthy control participants during a pharmacological magnetic resonance imaging study. Participants received a single dose of a dopamine receptor agonist, pramipexole, and a dopamine receptor antagonist, amisulpride, in a randomised, double-blind, placebo-controlled, balanced, crossover design. Functional task-related connectivity was analysed taking a whole brain connectomics approach to identify networks that are differentially modulated by dopaminergic receptor functioning.
SUD patients showed widespread reductions in connectivity during both reward and loss value-based choices and outcomes, which were negatively correlated with the duration of stimulant drug use. Disturbances to functional brain connectivity in SUD patients during task performance were not modulated acutely by either amisulpride or pramipexole.
Reductions in brain connectivity, particularly when making value-based choices and processing outcomes, may underlie learning impairments in SUD patients. Given that acute dopaminergic modulation did not improve brain connectivity impairments in SUD patients, it is likely that alternative treatments are needed.
患有兴奋剂使用障碍(SUD)的患者在进行基于价值的选择时会出现障碍,这与大脑网络中神经处理的中断有关。做出最佳选择需要从结果中学习,以更新知识并进一步优化正在进行的行为。支持做出有利选择的神经系统的最佳功能是生活功能的重要组成部分,也是 SUD 患者成功康复的关键。因此,我们试图研究 SUD 患者进行基于价值的选择所依赖的神经过程。我们假设 SUD 患者在进行概率强化学习任务时进行财务选择时,其功能连接会减少。
我们在一项药理学磁共振成像研究中调查了 SUD 患者和健康对照组参与者在进行基于损失和奖励的选择及其结果时与连接相关的情况。参与者以随机、双盲、安慰剂对照、平衡、交叉设计的方式接受了单一剂量的多巴胺受体激动剂普拉克索和多巴胺受体拮抗剂氨磺必利。通过全脑连接组学方法分析功能任务相关连接,以确定受多巴胺受体功能调节的网络。
SUD 患者在进行奖励和损失价值选择及其结果时,其连接普遍减少,并且与兴奋剂药物使用时间呈负相关。在任务执行过程中,SUD 患者的大脑功能连接障碍并未被氨磺必利或普拉克索急性调节。
大脑连接的减少,尤其是在进行基于价值的选择和处理结果时,可能是 SUD 患者学习障碍的基础。鉴于急性多巴胺能调节并不能改善 SUD 患者的大脑连接障碍,可能需要替代治疗方法。