Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits—pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen—brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.

经常吸毒会导致上瘾，但并不是每个吸毒的人都会经历这种转变。滥用药物究竟如何与个人脆弱性相互作用尚不完全清楚，也不清楚个人如何对抗与药物或成瘾脆弱性相关的风险。我们在 162 名参与者中使用静息状态功能 MRI (fMRI) 来描述暴露于兴奋剂药物的个体、成瘾个体的兄弟姐妹和对照志愿者中皮质纹状体功能回路的风险和恢复力相关变化。发展成瘾的可能性，无论是由于家庭脆弱性或吸毒，与眶额和腹内侧前额叶皮质 - 纹状体回路中的显着低连接性相关 - 这些途径与目标导向的决策密切相关。相比之下，对物质使用障碍诊断的复原力与两个网络中的超连接性相关，这些网络涉及 1）外侧前额叶皮层和内侧尾状核，以及 2）辅助运动区、上内侧额叶皮层和壳核——脑回路分别涉及自上而下的抑制控制和习惯的调节。这些发现指出了成瘾原因的易感性，与受损的目标导向行为有关，以及与行为调节有关的抵消弹性系统，并可能为治疗和预防干预提供新的策略。