前额叶神经振荡在甲基苯丙胺成瘾者自我控制中的作用及其机制研究

Methamphetamine addiction challenges public health severely. The addictive brain undergoes dramatic changes as a result of drug exposure. Accumulating evidence has demonstrated a wide range of brain areas, including ventromedial prefrontal cortex (VMPFC), medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC) and other subcortical regions, namely anterior cingulate cortex (ACC), striatum, and anterior insula, are involved in addiction. Previous studies have suggested that the impairment of frontal-striatum circuits resulting in damaged self-control on methamphetamine dependents. Our preliminary results have shown that methamphetamine addiction is associated with impaired inhibition control, decreased frontal gamma power and increased beta power in resting electroencephalograph (EEG) state.Yet the dynamic cortical network changes and neuropsychological functions during abstinence have not been fully elucidated. In present study, we aim to investigate the oscillation dynamics underlying self-control (e.g. inhibition, attention and cognitive control) on methamphetamine dependents using behavior measures and task-related EEG. The neural oscillation mechanism of addicts during abstinence may be neurobiological markers for the pathophysiology of methamphetamine addiction. Based on dysfunction of neural oscillation, the optimal noninvasive brain stimulation (oscillatory transcranial magnetic stimulation, TMS) can be conducted for reducing addiction-related interference in self-control, which may allow development of individualized TMS treatment protocols on methamphetamine dependents.

甲基苯丙胺成瘾是一种常见的物质成瘾。研究者们运用行为学实验，功能磁共振成像和头皮脑电记录等技术探究了成瘾对自我控制的影响及其动态神经活动。大量研究成果显示，成瘾伴随前额叶-纹状体网络的损伤严重影响了成瘾人群的自我控制功能。前期工作表明，甲基苯丙胺成瘾人群的抑制控制能力减弱，静息状态下前额叶皮层Gamma(30-50Hz)能量减弱和Beta(13-30Hz)能量增强。然而，成瘾人群前额叶神经振荡活动变化如何影响其自我控制尚不清楚。本研究综合行为学任务和同步高密度脑电记录的方法研究不同戒断时期甲基苯丙胺成瘾人群自我控制(包括：行为、注意和认知控制)的神经振荡基础，以及前额叶与顶叶等脑区间神经振荡相位同步化水平的变化。通过研究成瘾对前额叶神经振荡的影响，了解伴随自我控制功能的前额叶神经振荡的变化，并设计特异性的振荡式神经调控方法(周期性经颅磁刺激)，探索成瘾干预的个体化和精准化应用。

甲基苯丙胺(俗称“冰毒”)是我国滥用“头号毒品”，给社会和经济带来了严重的负担。既往研究表明：药物成瘾伴随前额叶-纹状体脑网络损伤，损害了成瘾人群的自我控制功能，导致高渴求和复吸行为。在本研究中，1.构建了甲基苯丙胺成瘾者自我控制功能改变的认知评估新范式，并在大样本（超过300人）成瘾队列中验证；2.在横断面研究（样本量156）中，发现伴随自我控制功能的改变，成瘾者的心理渴求在戒断期呈现出先上升后下降的趋势，同时发现内侧前额叶皮层Beta神经振荡、内侧前额叶皮层与眶回环路在脑区功能连接上表现出Beta振荡同步化增强，与行为（渴求）和认知（自我控制）变化高度相关; 3.在纵向研究（样本量116人）中，纳入自然戒断期组和不同的非侵入脑刺激干预组，发现内侧前额叶皮层Beta振荡介导自我控制功能和渴求的变化，基于脑网络的分析进一步揭示了成瘾临床干预中有效组和无效组的大规模神经振荡特异性脑网络机制：内侧前额叶皮层与左侧顶内沟和右侧脑岛环路在Beta频段的脑区功能连接因果性的参与该过程的变化。本项目通过研究成瘾对自我控制和前额叶神经振荡的影响，揭示了伴随渴求（自我控制功能）的认知和神经振荡机制，为临床成瘾干预的振荡式神经调控和闭环调控提供基础，促进成瘾干预的个体化和精准化应用。