Center for Neural Science, New York University, New York, NY, USA.
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Addict Biol. 2019 Jan;24(1):88-99. doi: 10.1111/adb.12545. Epub 2017 Sep 5.
The neurobiological mechanisms that underlie the resistance of drug cue associations to extinction in addiction remain unknown. Fear extinction critically depends on the ventromedial prefrontal cortex (VMPFC). Here, we tested if this same region plays a role in extinction of non-fear, drug and pleasant cue associations. Eighteen chronic cocaine users and 15 matched controls completed three functional MRI scans. Participants first learned to associate an abstract cue (the conditioned stimulus, CS) with a drug-related (CS ) or pleasant (CS ) image. Extinction immediately followed where each CS was repeatedly presented without the corresponding image. Participants underwent a second identical session 24 hours later to assess retention of extinction learning. Results showed that like fear extinction, non-fear-based extinction relies on the VMPFC. However, extinction-related changes in the VMPFC differed by cue valence and diagnosis. In controls, VMPFC activation to the CS (which was unpleasant for participants) gradually increased as in fear extinction, while it decreased to the CS , consistent with a more general role of the VMPFC in flexible value updating. Supporting a specific role in extinction retention, we further observed a cross-day association between VMPFC activation and skin conductance, a classic index of conditioned responses. Finally, cocaine users showed VMPFC abnormalities for both CSs, which, in the case of the CS , correlated with craving. These data suggest a global deficit in extinction learning in this group that may hinder extinction-based treatment efforts. More broadly, these data show that the VMPFC, when functionally intact, supports extinction learning in diverse contexts in humans.
成瘾中药物线索关联对消退的抵抗的神经生物学机制尚不清楚。恐惧消退关键依赖于腹内侧前额叶皮层（vmPFC）。在此，我们测试了同一区域是否在非恐惧、药物和愉悦线索关联的消退中起作用。18 名慢性可卡因使用者和 15 名匹配的对照者完成了三次功能磁共振扫描。参与者首先学习将一个抽象线索（条件刺激，CS）与一个与药物相关的（CS ）或愉悦的（CS ）图像相关联。随后立即进行消退，其中每个 CS 都反复呈现而没有相应的图像。参与者在 24 小时后进行第二次相同的会话以评估消退学习的保留。结果表明，与恐惧消退一样，非恐惧基础的消退依赖于 vmPFC。然而，vmPFC 与线索效价和诊断相关的消退相关变化不同。在对照者中，vmPFC 对 CS 的激活（对参与者来说是不愉快的）逐渐增加，就像在恐惧消退中一样，而对 CS 的激活则减少，这与 vmPFC 在灵活的价值更新中的更一般作用一致。支持在消退保留中具有特定作用，我们进一步观察到 vmPFC 激活与皮肤电导率之间的跨日关联，皮肤电导率是条件反应的经典指标。最后，可卡因使用者对两种 CS 都表现出 vmPFC 异常，而 CS 与渴望相关。这些数据表明该组在消退学习中存在普遍缺陷，这可能会阻碍基于消退的治疗努力。更广泛地说，这些数据表明 vmPFC 在功能完整的情况下，支持人类在不同环境中的消退学习。
