意识障碍患者大脑感觉-认知神经机制及其神经调控治疗研究

Improvement of cardiopulmonary resuscitation and intensive care in medical technology leads to an increasing number of patients with disorders of consciousness (DOC) after severe brain injury. However, until now no standardized differential diagnosis, prognostic indicator or evidence-based guidelines on treatment has been constructed. Our previous study has successfully obtained a hierarchical auditory event-related potential (ERP) pattern, indicating that the approach could be used as a valuable tool to evaluate patients with DOC. The current study proposes the hypothesis that the noninvasive brain stimulation could improve consciousness level in patients with DOC by improving the sensory-cognitive processing and improving the glucose metabolism and blood perfusion in different regions of brain networks. In the current study, we use ERP combined with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), and further use noninvasive brain stimulation to stimulate the key brain area, from the auditory processing, speech perception processing to semantic processing, to deeply explore the difference of sensory-cognitive processing mechanism to the auditory stimulus under passive and active condition. In the FDG-PET study, we observe the difference of glucose metabolism and blood flow perfusion of the brain high-level and low-level network, and to clarify the correlation between different brain networks and behavioral scores in patients with DOC. We further combine etiology, time since insult and position of damage to obtain a comprehensive understanding of the therapeutic efficacy of the noninvasive brain stimulation. The study will optimize the parameters of noninvasive brain stimulation, and define the mechanism of functional reorganization of brain, and provide theoretical basis for clinical neuromodulation therapy to patients with DOC.

随着心肺复苏和重症监护医学技术的进步，严重脑损伤后存活的意识障碍患者逐年增多，目前对其鉴别诊断、预后预测及促醒仍无明确标准。课题组前期创立了两组难度递阶式增加的听觉范式，并在其鉴别诊断及预后预测中得到初步应用。本项目提出假说：非侵入性脑刺激可通过对患者大脑感觉-认知加工过程及不同脑网络脑区葡萄糖代谢和血流灌注改善而提升意识水平。研究联合事件相关电位和18F-脱氧葡萄糖正电子发射计算机断层脑显像技术，并利用非侵入性脑刺激技术刺激关键脑区，从低级听觉处理、语音感知处理和语义加工处理三方面探讨患者在被动及主动情况下对听觉刺激的感觉-认知加工机制差异，观察大脑高级和低级网络关键脑区葡萄糖代谢及血流灌注差异，明确不同脑网络功能与行为学评分及预后的相关性，并依据病因、病程、病损部位进行分类深入探讨作用机制，以期优化刺激参数，明确对患者大脑功能重组的作用机制，为临床开展神经调控治疗提供理论依据。

随着心肺复苏技术和重症监护医学技术的快速发展，使得从严重脑损伤后存活下来的慢性意识障碍患者数量逐年增加，由此带来诸多伦理及法律问题等。本研究联合行为学评估量表、事件相关电位（ERP）和18F-脱氧葡萄糖正电子发射计算机断层脑显像技术（FDG-PET）等评估手段，并利用非侵入性脑刺激技术刺激意识网络关键脑区，从低级听觉处理、语音感知处理和语义加工处理三方面探讨患者对听觉刺激的感觉-认知加工机制变化，观察大脑高级和低级网络关键脑区葡萄糖代谢及血流灌注差异。主要结果如下（1）通过双中心前瞻队列研究收集意识障碍患者临床数据，阐明慢性意识障碍患者流行病学概况，揭示自然病程规律；并通过对不同意识水平意识障碍患者静息功能磁共振研究发现默认模式网络关键脑区的脑功能活动和结构性重塑以及小脑的激活水平与临床行为表现存在相关性，对患者的预后预测方面的潜在应用价值；（2）研究发现经颅直流电刺激（tDCS）治疗可在组水平上改善微意识状态（MCS）患者的意识水平，对无反应觉醒综合征/植物状态（UWS/VS）患者则无明显改善作用，我们通过ERP技术和FDG-PET技术从电生理和功能影像学方面阐明了MCS患者较UWS/VS患者tDCS疗效较好的机制，并发现更高的改良昏迷恢复量表（CRS-R）评分和分层听觉ERP范式中P300的存在，特别是DO范式中的P300成分与MCS患者的tDCS响应性有关，初步阐明tDCS干预显效意识障碍患者的神经特征。本研究的结果对揭示意识障碍的神经机制，探索对脑损伤后意识障碍更为安全、高效的神经调控治疗策略将具有极为重要的意义和临床实用价值。