Zhang Yi, Li Qiang, Wen Xiaotong, Cai Weiwei, Li Guanya, Tian Jie, Zhang Yi Edi, Liu Jixin, Yuan Kai, Zhao Jizheng, Wang Wei, Zhou Zhenyu, Ding Mingzhou, Gold Mark S, Liu Yijun, Wang Gene-Jack
School of Life Science and Technology, Xidian University, Xi'an, China.
Department of Psychiatry & McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Addict Biol. 2017 Jul;22(4):1068-1080. doi: 10.1111/adb.12390. Epub 2016 Mar 14.
Resting-state magnetic resonance imaging has uncovered abnormal functional connectivity in heroin-dependent individuals (HDIs). However, it remains unclear how brain regions implicated in addictions are related in baseline state without conditioned cues in heroin dependent individuals during opioid maintenance treatment (HDIs-OMT). Previous connectivity analysis assessed the strength of correlated activity between brain regions but lacked the ability to infer directional neural interactions. In the current study, we employed Granger causality analysis to investigate directional causal influences among the brain circuits in HDIs-OMT and non-opioid users. The results revealed a weaker effective connectivity between the caudate nucleus implicated in mediating the reward circuit and other brain regions and also a weaker connectivity between the anterior cingulate cortex and medial prefrontal cortex implicated in mediating inhibitory control. Conversely, HDIs-OMT exhibited stronger effective connectivity between the hippocampus and amygdala implicated in mediating learning-memory, and the anterior cingulate cortex involved in mediating inhibitory control while the putamen mediated learned habits, suggesting that the hippocampus and amygdala may propel the memory circuit to override the control circuit and drive the learned habit in HDIs-OMT. Alterations in learning-memory and inhibitory control may contribute jointly and form a basis for relapse risk even after a period of heroin abstinence. Sustained neural effect of opioid dependence on methadone maintenance including hyperactivation in the memory circuit and impairment in the control circuit support the role of the memory circuitry in relapse and may help redefine targets for treatment.
静息态磁共振成像已发现海洛因依赖个体（HDIs）存在异常功能连接。然而，在阿片类药物维持治疗期间（HDIs-OMT），在没有条件线索的基线状态下，海洛因依赖个体中涉及成瘾的脑区之间是如何关联的仍不清楚。以往的连接性分析评估了脑区之间相关活动的强度，但缺乏推断方向性神经相互作用的能力。在本研究中，我们采用格兰杰因果分析来研究HDIs-OMT和非阿片类药物使用者脑回路之间的方向性因果影响。结果显示，在介导奖赏回路的尾状核与其他脑区之间，有效连接较弱，在介导抑制控制的前扣带回皮质和内侧前额叶皮质之间，连接也较弱。相反，HDIs-OMT在介导学习记忆的海马体和杏仁核之间，以及在介导抑制控制的前扣带回皮质与介导习得习惯的壳核之间，表现出更强的有效连接，这表明海马体和杏仁核可能推动记忆回路凌驾于控制回路上，并驱动HDIs-OMT中的习得习惯。即使经过一段时间的海洛因戒断，学习记忆和抑制控制的改变可能共同起作用，并形成复发风险的基础。阿片类药物依赖对美沙酮维持治疗的持续神经效应，包括记忆回路的过度激活和控制回路的损害，支持了记忆回路在复发中的作用，并可能有助于重新确定治疗靶点。
