Clinical Applications and Potential Mechanisms of Repetitive Transcranial Magnetic Stimulation in Prolonged Disorders of Consciousness
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摘要: 慢性意识障碍（pDoC）病情复杂且病程长，严重影响患者的预后，是目前临床治疗的难点。近年来，基于神经调控机制的促醒疗法在pDoC患者的评估及诊疗中运用广泛。重复经颅磁刺激（rTMS）技术通过调节患者的神经活动，进而改善意识状态，对pDoC患者具有积极的促醒疗效。但rTMS的最佳刺激参数和促醒机制尚未明确。对pDoC的病理机制、rTMS不同靶点和刺激频率的临床应用进行系统综述，重点探讨rTMS通过改变神经通路和重塑脑网络、促进突触可塑性和神经递质释放、调节神经营养因子表达及调控脑血流动力学等神经机制促进意识恢复的作用，并基于人工智能展望rTMS在未来临床研究中的应用前景。Abstract: Prolonged disorders of consciousness （pDoC） are complex and prolonged conditions that severely impact patient prognosis and remain a clinical treatment challenge. In recent years, neural regulation-based awakening therapies have been widely applied in the assessment and treatment of pDoC patients. Repetitive transcranial magnetic stimulation （rTMS） technology can regulate neural activity and improve patients' consciousness states, demonstrating positive awakening effects for pDoC patients. However, the optimal stimulation parameters and awakening mechanisms of rTMS remain unclear. This article reviews the pathological mechanisms of pDoC, clinical applications of rTMS at different targeting sites and stimulation frequencies, and focuses on exploring how rTMS promotes consciousness recovery through neural mechanisms such as altering neural pathways, reshaping brain networks, promoting synaptic plasticity and neurotransmitter release, regulating neurotrophic factor expression, and modulating cerebral hemodynamics. Based on artificial intelligence, the article also prospects the future clinical research applications of rTMS.
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表 1 不同靶点与频率rTMS治疗慢性意识障碍的临床研究
Table 1. Clinical studies of rTMS with different targets and frequencies in pDoC
被试者 刺激靶点 刺激频率 调控参数 治疗周期 主要结果 参考文献 99例VS 患侧M1 20 Hz 90% RMT，8000脉冲 4周 临床和神经生理反应明显改善 [22] 6例pDoC 左侧M1 20 Hz 100% RMT，1000脉冲 5 d 仅1例患者有行为改善和EEG变化 [23] 7例pDoC
11例健康人左侧M1 20 Hz 100% RMT，1000脉冲 5 d 1例MCS患者的CRS-R评分升高，
功能连接明显增强[24] 11例VS 左侧M1 20 Hz 90% RMT，1000脉冲 4周 行为和脑电均无明显改善 [39] 20例pDoC 右侧DLPFC 5 Hz - 4周 6例患者意识和行为改善 [37] 10例健康人
10例UWS右侧DLPFC 10 Hz 90% RMT，1000脉冲 1次 3例UWS患者出现短暂临床改善 [25] 32例VS 右侧DLPFC 10 Hz 100% RMT，1575脉冲 20 d 增加CRS-R评分，降低MEP和CMCT [26] 50例pDoC 左侧DLPFC 10 Hz 90% RMT，1000脉冲 6周 神经行为和电生理指标明显改善 [27] 8例MCS / UWS 左侧DLPFC iTBS 80% RMT，600脉冲 5 d CRS-R评分和脑电改善明显 [41] 11例pDoC 楔前叶 10 Hz 90% RMT，1200脉冲 2周 神经行为和静息态脑电改善 [32] 16例VS
22例MCS左侧角回 20 Hz 80% RMT，3200脉冲 2周 MCS患者的CRS-R总分改善 [35] 26例pDoC 顶叶 10 Hz 90% RMT，1000脉冲 2周 行为和脑电改善明显 [36] 
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