基于意识障碍患者对听刺激的皮层反应对其进行评估及清醒预测的研究

Disorders of consciousness is a common symptom after severe brain injury. Some patients can regain consciousness, but some patients will be vegetative state or minimally conscious state forever. It's difficult to discriminate vegetative state and minimally conscious state, which prevents us to do treatment plan and recovery prediction. Now, the discrimenation is limited to clinical manifestation and scale test, which are far from accurate. So a pressing matter of the moment is to find objective methods to discrimenate them correctly. Previous studies about disorders of consciousness with event related potential (ERP) and functional magnetic resonance imaging (fMRI) have not yet drawn definite conclusions.Our project planned to do 10 kinds of experiments, which were divided into two categories: (1)discrimenation of vegetative state and minimally conscious state; (2) recovery prediction of disorders of consciousness. There are three kinds of stimuli in ERP and fMRI experiments:pure tone, subjects' own name and reversed subjects' own name which is an innovation of our project. In the ERP experiment, we observe the changes of P300 and MMN with the above-mentioned stimuli as standard or deviant stimuli. In the fMRI experiment, we set them as tasks to get task state image and we also do resting state scan, then we compare the different brain regions activated among subjects. By studying the relationship between these indexes and consciousness, also with scale tests and follow-up, we try to find objective indexes and theory to discrimenate and predict the prognosis of vegetative state and minimally concious state.

意识障碍是严重脑损伤后的常见症状，部分患者可以清醒，但部分患者将持续处于植物状态或最小意识状态。两者很难鉴别,给治疗方案制定和清醒预测带来不便。目前两者的鉴别仅限于临床表现和量表测验，很不准确，故客观准确地鉴别两者并进行清醒预测甚为重要。此前用事件相关电位（ERP）、功能磁共振（fMRI）等方法进行的研究尚未得到定论。本项目拟进行十项实验，分为两类：（1）植物状态和最小意识状态的鉴别，（2）意识障碍的清醒预测。采用ERP和fMRI方法，刺激分为三种：纯音、受试者名字和本项目创新的受试者倒序名字。在ERP实验中将其组合为不同的标准刺激、偏差刺激，观察P300、MMN等成分的变化。在fMRI实验中，以其为任务进行任务态扫描，并兼行静息态扫描，对比脑区激活差异。通过研究这些客观指标与意识之间的关系，辅以量表测验、跟踪随访等全方位研究，寻求出两者的鉴别与预后的客观而更为准确的指标及应用理论。

意识障碍是严重脑损伤后的常见症状，部分患者可以清醒，但部分患者将持续处于植物状态或最小意识状态，两者很难鉴别，故给治疗方案制订和清醒预测带来不便。本项目利用事件相关电位（ERP）和功能磁共振（fMRI）结合行为学数据，并利用先进的非侵入性脑刺激技术，进行如下研究并得到相应结果：（1）采用最熟悉人呼唤受试者本人名字（SON）及创新性结合本人反名（rSON）、纯音等作为听觉刺激，创立新型听觉刺激范式，利用ERP首先在健康受试者中客观定量脑功能网络，建立正常参考体系，为后续意识障碍患者脑功能评估提供参考依据；（2）进一步将该ERP听觉范式应用于意识障碍患者，定量评估残存意识水平，发现不同意识水平患者对听刺激的大脑加工机制差异，通过随访研究确定P300波形这一电生理学指标与预后的相关性，为临床预后评估提供重要的客观电生理学依据。（3）进一步细化意识障碍患者的分类，除植物状态患者和最小意识状态患者外加入了严重脑损伤后昏迷1月内清醒的患者及闭锁综合征患者，利用fMRI深入探讨不同意识水平患者意识网络激活区域，探明意识维持关键脑区；（4）利用经颅直流电刺激（tDCS）技术对意识障碍患者进行干预治疗，并利用ERP深入探讨其作用机制，发现对最小意识状态患者左侧DLPFC区域的重复tDCS刺激可改善其行为学表现，猜测tDCS对患者作用可能是通过对关键脑区的刺激从而增强注意资源分配水平，结果支持ERP可作为床旁可靠的疗效评估工具，并支持tDCS的临床推广应用。综上，本研究的结果对揭示意识维持与损伤的神经机制，探索对改善意识水平的新型神经调控治疗策略具有极为重要的科学意义和临床实用价值。