基于脑磁图源重构技术研究精神分裂症言语性幻听的动态网络机制

The real-time changes of brain activity in patients with schizophrenia before and during auditory hallucinations may play an important role in revealing the auditory hallucinations. Functional magnetic resonance studies found that patients presented abnormalities in auditory, language, and memory network connections at this stage, but the device limited dynamic research on the auditory hallucination processing due to temporal resolution. For example, the interaction mechanism between language networks and auditory and memory networks is not known. The dynamic network connection model can reveal the changing rules of brain activity and help to explore the relationship between these three networks. The previous study of our teams found that the abnormal connection between the auditory network and the language network of the auditory hallucinations decreased, and the primary auditory cortex and the anterior wedge were inhibited. This study selects those patients with high-frequency auditory hallucinations. Based on magnetoencephalography with high temporal resolution, high signal-to-noise ratio and noise-free environment, the patients are recorded during auditory hallucinations and no auditory hallucinations. This project intends to use the magnetoencephalography source reconstruction method designed by the applicant in the early stage to construct a real-time cortical network. Through comparative analysis, observe the sequence and interaction of the three network activation or suppression, and reveal the dynamic network mechanism of auditory hallucinations. The successful implementation of the project is expected to provide important clues for elucidating the pathological mechanism of auditory hallucinations in schizophrenia.

精神分裂症患者在幻听发生前和发生期间大脑活动的实时变化规律可能对揭示幻听机制起到重要作用。功能磁共振研究发现患者在这一阶段呈现听觉、语言和记忆网络连接异常，但该设备由于时间分辨率限制了对幻听过程的动态研究。例如，语言网络与听觉、记忆网络的交互机制尚未知。动态网络连接模式能揭示大脑活动过程的变化规律，有助于探索这三个网络之间的关系。本团队前期研究发现，幻听患者听觉网络和语言网络的协同连接下降，初级听觉皮层与楔前叶抑制连接减弱。本项目选取言语性幻听频率高发的精分患者为研究对象，基于高时间分辨率、高信噪比和无噪声环境的脑磁图技术，记录患者在发生幻听期间和未发生幻听但给予模仿幻听内容刺激下的两类数据，拟采用申请人在前期设计的脑磁图源重构方法，构建实时皮层网络，通过对比分析，观察三个网络激活或抑制的顺序及交互影响，揭示幻听的动态网络机制。项目顺利实施有望为阐明精神分裂症幻听的病理机制提供重要线索。

言语性幻听为精神分裂症重要阳性症状，患者在幻听发生前和发生期间大脑活动的实时变化规律对揭示幻听机制起到重要作用。考虑到抗精神病药物可能会对大脑神经活动有影响，为了尽可能降低药物的作用，本研究入组被试为首发患者（FES）和临床高危综合症（CHR）人群，同时伴有言语性幻听症状。应用脑磁图技术，记录被试发生幻听和未发生幻听阶段数据，采用的任务是当幻听状态发生时，被试开始按键，当幻听状态结束时，结束按键。采用项目负责人设计的脑磁图源重构方法，构建皮层动态网络，通过对比分析，观察听觉网络、语言网络、记忆网络激活或抑制的顺序及交互影响，揭示幻听的动态网络机制。.本研究共收集42例有幻听症状的FES和CHR数据，其中在检查中捕捉到幻听症状有26例。重要研究结果有：（1）对比分析FES和CHR被试的幻听发生与未发生阶段的脑磁图数据，时频分析结果表明幻听发生与theta与beta信号密切相关，幻听发生时刻，beta频段的能量谱信号明显增强，theta频段的能量谱在幻听患者明显增强。通过构建幻听发生的动态网络模型，发现幻听从发生前到幻听发生阶段，皮层激活区域依次描述为：首先皮层Broca区和Wernicke区激活，其次Broca区减弱、Wernicke区增强、楔前叶区激活，然后Wernicke区减弱、楔前叶区和Broca区激活消失，再次颞上回（STG）和顶下小叶激活，最后消失在Wernicke区。这些区域可能涉及到听觉网络（Broca区和STG区）、语言网络（Wernicke区、Broca区）、记忆网络（楔前叶区、顶下小叶），结论为Wernicke区在整个幻听发生过程中起着重要作用，也起到衔接听觉和记忆网络。（2）设计出一种新的特征用于检测FES，提出一种新的客观标志物的方法，灵敏度提高了近2倍，特异性几乎未降低，准确率也有大幅度提高。（3）设计一种脑磁图方法来检测CHR的异常特征所对应的脑区，结果表明在theta和delta两个频段信号异常，异常的区域涉及到左侧颞枕交界区、右侧背外侧前额叶、眶额叶区域。.本研究揭示了幻听机制，对下一阶段幻听的干预治疗中最重要的环节——确定靶点，有着重要指导价值。