TMS干预联合情绪刺激对意识障碍患者额顶神经网络的影响与机制

Recent advances have demonstrated the activity and complex functional interconnections within widespread network play an important role in consciousness. However, the value of network assessment for diagnosis and prognosis remains a challenge. Our previous work showed in patients with disorders of consciousness(DOC), the perturbations of brain network connectivity varied according to different etiology, as the traumatic subjects suffered from greater connectivity reduction than nontraumatic subjects, especially the top-down influences. Moreover, reviewing existing studies, transcranial magnetic stimulation(TMS) has been proposed as an experimental approach for the treatment of disorders of consciousness(DOC), however, there has been little research into the mechanism of TMS in DOC and the therapeutic effects have been inconsistently documented which may be due to the individual difference in anatomy. Hence, our research, based on the hypothesis that perceptual processing of emotionally significant stimuli was prioritized and the affective condition activated wider brain areas, monitors the dynamic brain effective connectivity combining electroencephalography(EEG) and functional magnetic resonance imaging(fMRI) underlying emotional sound exposure, aiming to explore the efficiency of TMS stimulating at traditionary or individualized targets on frontoparietal network in patients with DOC. Finally, by providing neural characterization of frontoparietal connectivity in states of consciousness with multidimensional assessments, we speculate the specific network may have novel potential for informing diagnosis and prognosis in DOC and even be the target for treatment intervention, particularly for patients with traumatic injuries.

脑网络对意识障碍准确鉴别、预后评估、干预促醒的应用价值是现代神经科学研究的重点与难点，近年研究发现意识水平与脑网络连接存在一定关联。本项目组前期工作发现不同病因损伤导致意识障碍患者脑网络连接存有差异，其中脑外伤患者额顶网络损伤尤为严重。既往研究提示经颅磁刺激对意识障碍促醒有效，但其刺激靶点易受个体差异影响且促醒机制尚不明确。为此，本课题组结合前期基础，求证“经颅磁刺激疗法可通过改变额顶网络提高脑外伤后意识障碍患者的意识水平”的假说，并进一步探究经典刺激靶点与个体化靶点的疗效差异。基于意识障碍患者对情绪刺激反应的高敏感性，拟借助于情绪刺激下脑外伤后意识障碍患者的脑电效应网络和功能磁共振网络分析，对经颅磁刺激治疗前后的神经电生理和神经影像标记物的改变进行量化评估，从多层次的网络水平揭示额顶网络的连接特征，及其参与意识水平改变的神经机制，为脑外伤后意识障碍的准确评估和个体化促醒手段提供新思路。

脑网络对意识障碍准确鉴别、预后评估、干预促醒的应用价值是现代神经科学研究的重点与难点。课题组前期研究发现脑网络在意识障碍发病过程中可能发挥特定的作用。在此基础上，本研究对听觉刺激下意识障碍患者的脑电信号或磁共振信号进行脑网络分析，并采用经颅直流电刺激与节律性音乐-电TNS作用于意识障碍患者的特定刺激位点，分析神经调控前后脑网络情况，从听觉刺激与神经调控干预两个角度揭示意识障碍的脑网络连接特征，并初步阐明其参与意识障碍发病过程的神经机制，本项目的主要发现如下：（1）意识障碍患者基本保存统计学习能力与语音包络的皮层响应能力，delta频段刺激锁定的神经活动增加是意识障碍患者意识改善的标志；（2）意识障碍患者丘脑白质的改变主要位于背内侧核、前核和腹前核，意识障碍患者中得连接前额叶、颞叶和感觉运动皮质的丘脑皮质通路受损，提示其可能参与意识障碍的发病过程；（3）节奏性的音乐-电TNS刺激导致患者的大脑gamma节律性活动显著增加，进而显著改善DoC患者的意识，初步说明节奏性的音乐-电TNS刺激的意识促醒作用及该频段的节律性神经振荡参与意识障碍的发病过程。本项目的实施在慢性意识障碍患者的语音刺激脑电网络研究以及丘脑皮质振荡网络研究上取得了重要的阶段性成果。