Liu Zhenyu, Wu Shanshan, Wang Shuwei, Wu Huijuan, Gao Hongliang, Lu Xiao
Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Jiangsu, China; Key Laboratory of Ultra-Weak Magnetic Field Measurement Technology, Ministry of Education, School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, China.
Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, China.
Neuroimage Clin. 2025;46:103802. doi: 10.1016/j.nicl.2025.103802. Epub 2025 May 10.
Disorders of consciousness (DoC) are characterized by a broad decline in background excitatory synaptic activity and varying levels of cerebral network disruption. Repetitive transcranial magnetic stimulation (rTMS), a neuromodulatory technique, is anticipated to assist the recovery of consciousness. Nonetheless, ongoing debates persist regarding its effectiveness, in light of the inconsistent results of recent research.
The purpose of this study is to investigate the efficacy of rTMS in promoting recovery of consciousness in patients with DoC and to probe its impact on activity of cerebral functional networks.
Forty-eight patients with DoC were included in this randomized controlled trial (Chinese Clinical Trial Registry: ChiCTR2100044930). Twenty-four patients in the control group accepted conventional therapy. Another 24 patients in the rTMS group received extra rTMS over the dorsolateral prefrontal cortex (DLPFC) once per workday during a 4-week intervention phase. Primary outcome was the proportion of patients emerging improvement on level of consciousness (LOC) based on coma recovery scale- revised (CRS-R) at the end of intervention. Furthermore, other behavioral scales such as the clinical global impression-improvement (CGI-I) and resting state-electroencephalography (rs-EEG) microstate were employed as secondary outcomes. Different microstates served as tools to detect the activity of respective corresponding resting state cerebral functional networks.
In comparison to the control group, the rTMS group exhibited a higher proportion of patients emerging improvement on LOC at post-intervention, with a risk ratio of 3.06 (95 % CI 1.54 to 6.09, P = 0.001). The distribution of patients with each grade of CGI-I across the groups also implied a trend that favored the rTMS group (common odds ratio:0.20, 95 % CI 0.065 to 0.63, P = 0.006). With respect to microstate E, the rTMS group had a significantly reduced global explained variance (GEV) was observed in the rTMS group (Z = -2.61, P = 0.027).
High-frequency rTMS over the DLPFC could promote recovery of consciousness in patients with DoC. It might get involved in modulating the balance among cerebral functional networks and facilitating consciousness recovery.
意识障碍（DoC）的特征是背景兴奋性突触活动广泛下降以及脑网络破坏程度各异。重复经颅磁刺激（rTMS）作为一种神经调节技术，有望促进意识恢复。然而，鉴于近期研究结果不一致，关于其有效性的争论仍在持续。
本研究旨在探讨rTMS对DoC患者意识恢复的疗效，并探究其对脑功能网络活动的影响。
本随机对照试验纳入了48例DoC患者（中国临床试验注册中心：ChiCTR2100044930）。对照组的24例患者接受常规治疗。rTMS组的另外24例患者在为期4周的干预阶段，每个工作日在背外侧前额叶皮质（DLPFC）接受一次额外的rTMS治疗。主要结局是干预结束时基于昏迷恢复量表修订版（CRS-R）意识水平（LOC）出现改善的患者比例。此外，还采用了其他行为量表，如临床总体印象改善量表（CGI-I）和静息态脑电图（rs-EEG）微状态作为次要结局。不同的微状态作为检测各自相应静息态脑功能网络活动的工具。
与对照组相比，rTMS组在干预后LOC出现改善的患者比例更高，风险比为3.06（95%CI 1.54至6.09，P = 0.001）。各等级CGI-I患者在组间的分布也显示出有利于rTMS组的趋势（共同优势比：0.20，95%CI 0.065至0.63，P = 0.006）。关于微状态E，rTMS组的全局解释方差（GEV）显著降低（Z = -2.61，P = 0.027）。
DLPFC区域的高频rTMS可促进DoC患者的意识恢复。它可能参与调节脑功能网络之间的平衡并促进意识恢复。
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