高频重复经颅磁刺激对海洛因成瘾的治疗作用及其脑机制

Heroin addiction is characterized by compulsive use, low recovery rate and high recurrence rate. It is difficult to target the neural circuits that related to addiction, so the effects of conventional pharmacotherapy and psychotherapy on heroin addiction were extremely low. The repetitive transcrainal magnetic stimulation(rTMS) has the advantage of precisely targeting addiction neural circuits. High-frequency rTMS over the dorsolateral prefrontal cortex(DLPFC) has been reported to improve addiction with an immediate effect. Our previous study reported that the left DLPFC high- frequency rTMS could instantly reduce carving for heroin in addicts. However, the answer for whether the high-frequency rTMS over the different stimulated location could produce different effect on improve heroin addiction remain unknown. Moreover, what is the brain mechanism of the high-frequency rTMS over the DLPFC to treat heroin addiction? Whether the rTMS could reduce craving for heroin through activating the DLPFC involved in addiction and changing the functional connection between DLPFC and related brain areas? How long can this effect maintain? All these problems need to be further defined. This study will compare the stimulated effect on reducing heroin craving over the left, right and bilateral DLPFC, and follow-ups will be conducted to evaluate its long-term effect. The influence of high frequency rTMS on neural circuits related to addiction will be explored in this study using functional magnetic resonance imaging technology.

海洛因成瘾以强制性使用、低康复率、高复发率为主要特征。常规药物和心理治疗对海洛因成瘾的疗效差，原因是无法精确作用于成瘾相关的神经环路。重复经颅磁刺激（rTMS）的优势是可以精确作用于成瘾相关的神经环路，有研究表明高频rTMS作用于左侧前额叶背外侧皮质（DLPFC）可以即刻改善物质成瘾，本课题组前期研究发现高频rTMS作用于海洛因成瘾者左侧DLPFC可以即刻降低对海洛因的渴求度。但是高频rTMS刺激位置的不同是否能对改善海洛因成瘾产生不同的效果？作用于DLPFC的高频rTMS治疗海洛因成瘾的脑机制是什么？是否通过提高成瘾相关脑区DLPFC的激活程度，改变其与相关脑区的功能连接来降低对海洛因的渴求度?这种效应能维持多长时间？都需要进一步明确。本研究将比较左侧、右侧及双侧DLPFC刺激对降低海洛因渴求度的疗效，对疗效进行长期随访，并结合功能磁共振成像技术探讨高频rTMS对成瘾相关神经环路的影响。

本项目旨在研究重复经颅磁刺激对毒品成瘾的治疗作用及其脑机制，重点研究了不同刺激靶点重复经颅磁刺激对海洛因成瘾、甲基苯丙胺成瘾渴求的改善程度及其神经机制。项目资助成果已在The American Journal on Addictions，Progress in Neuropsychopharmacology & Biological Psychiatry，CLINICAL AND TRANSLATIONAL MEDICINE, CNS & Neurological Disorders-Drug Targets期刊发表SCI论文4篇，在《中华物理医学与康复杂志》发表论文1篇，均标注由本项目资助，部分成果在分析投稿中。本项目研究结果表明作用于背外侧前额叶皮质的重复经颅磁刺激均能改善海洛因及甲基苯丙胺成瘾，且具有一定的长期效应。通过功能磁共振分析发现经过重复经颅磁刺激干预后，背外侧前额叶与运动前回/运动后回的功能连接显著升高。本项目研究成果在江苏、浙江等省各戒毒所得到大规模推广应用，疗效得到肯定。项目负责人主导撰写了浙江省地方标准《经颅磁刺激戒毒康复应用技术规范》（2020年1月21日发布）。项目经费严格按照预算执行，支付率超过70%。