HD-tDCS联合昼夜节律重塑对慢性意识障碍患者意识恢复的作用及机制研究

慢性意识障碍的有效治疗方法及其作用机制的探究是现代神经科学的重点和难点。现有的干预手段单一、作用靶点不明确，且重构慢性意识障碍患者整体脑网络作用不显著。本课题组前期发现慢性意识障碍患者存在不同程度的昼夜节律紊乱。既往研究发现光刺激等能以下丘脑为靶点重塑昼夜节律，且昼夜节律重塑与意识水平恢复密切相关。故我们将首先监测患者的睡眠、体温、激素水平，明确不同程度慢性意识障碍患者的昼夜节律变化。再运用空间分辨率高且电场聚焦较强的高清晰度经颅直流电刺激（HD-tDCS）作用于大脑楔前叶“自上而下”地激活皮层-皮层下通路；并采用昼夜节律重塑的方法“自下而上”地激活下丘脑-脑干-丘脑-皮层通路。最后结合电生理、多组学、神经影像静态动态联合分析综合判定；探究其对于慢性意识障碍患者的疗效及作用机制。明确下丘脑-脑干-丘脑-楔前叶-皮层下的促醒神经环路，为慢性意识障碍的治疗以及意识神经环路基础的探究提供新思路。

The effective treatment of chronic disorder of consciousnesss (cDOC) is one of the most challenging topics in the modern neuroscience and its underlying neural mechanism is still unclear. To date, the choice of interventions to cDOC is limited and the targets are not demonstrated. Moreover, the effect of intervention is equivocal. Aberration of circadian rhythm in patients with cDOC was observed in our previous study. Previous study found that the disruption of circadian rhythm could be recovered by photon stimulation of hypothalamus. And it is reported that the circadian rhythm is closely related to the level of consciousness Therefore，by monitoring the sleep, body temperature, and hormone levels, we try to identify the disruption of circadian rhythm in patients with different degree of consciousness impairment. Then, we attempt to awaken the patients by normalizing the circadian rhythm and stimulating the precuneus to activate the subcortical pathway (top to down) using high definition transcranial direct current stimulation (HD-tDCS) which has higher temporal resolution and stronger focused electric field than the traditional tDCS. Meanwhile, the methods of circadian remodeling are used to activate the neural pathway of hypothalamus-brainstem - thalamus-cortex (down to top). Combined with neuroimaging, electrophysical techniques, multi-omics, static and dynamic analysis approach, we will probe into the curative effect and mechanism of these intervention, as well as contain the nerve circuit of hypothalamic-pontine tegmental region-thalamus-precuneus-subcortical. Our study may shed a new light on promoting the awakening therapy and exploring the neural mechanism of consciousness.