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Background <p>Disorders of consciousness (DoC) represent complex clinical conditions following severe brain injury, for which conventional treatments show limited efficacy. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has emerged as a promising intervention. However, existing evidence remains heterogeneous, necessitating a systematic integration of randomized controlled trials (RCTs) to clarify its therapeutic benefits. Pharmacological options such as amantadine remain limited, and outcomes often vary by etiology (e.g., traumatic vs. hypoxic–ischemic injury), underscoring the need for neuromodulatory approaches such as rTMS.</p> Methods <p>Following the PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Cochrane Library, and other databases for articles published up to July 2025. RCTs involving DoC patients receiving rTMS (targeting the dorsolateral prefrontal cortex, DLPFC) compared to sham stimulation, with changes in Coma Recovery Scale-Revised (CRS-R) scores as the outcome, were included. Methodological quality was assessed using the Cochrane RoB 2.0 tool. Statistical analyses were performed in R with the ‘meta’ package, using standardized mean difference (SMD) and 95% confidence intervals (CI) to estimate effect sizes. Sensitivity analysis was conducted via the leave-one-out method, and publication bias was evaluated using funnel plots.</p> Results <p>Six RCTs comprising 274 DoC patients were included. Meta-analysis indicated that rTMS did not significantly improve post-intervention CRS-R total scores (SMD = 1.31, 95% CI –0.41 to 2.76). However, rTMS significantly increased the change in CRS-R scores (ΔCRS-R, SMD = 1.33, 95% CI 0.51–2.15). Subgroup analysis revealed that both 10&#xa0;Hz (SMD = 1.46, 95% CI 0.14–2.78) and 20&#xa0;Hz (SMD = 1.10, 95% CI 0.71–1.50) stimulation frequencies were effective, with no significant difference between them (<i>χ</i><sup>2</sup> = 0.26, <i>p</i> = 0.611). Sensitivity analysis identified the study by He et al. (2021) as a major source of heterogeneity. After its exclusion, the effect size for CRS-R total scores reached statistical significance (SMD = 0.63, 95% CI 0.29–0.97). Funnel plots suggested the presence of publication bias, which was markedly reduced after excluding the outlier study.</p> Conclusion <p>rTMS targeting the DLPFC can significantly promote recovery of consciousness in patients with DoC, with both 10&#xa0;Hz and 20&#xa0;Hz frequencies demonstrating clinical potential. Future large-sample, standardized RCTs are warranted to reduce heterogeneity and identify biomarkers for predicting treatment response, thereby facilitating the precision application of rTMS in DoC.</p>

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Repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex promotes recovery of consciousness in patients with disorders of consciousness: a meta-analysis of randomized controlled trials

  • 期刊论文

  • 发表日期：

    2025年10月15日

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  • YiJing Gong,
  • Li Zhang,
  • Yan Zhang,
  • Jia Cao,
  • YueTing Wang,
  • Yuan Lei,
  • KeYing Zhu

摘要

Background

Disorders of consciousness (DoC) represent complex clinical conditions following severe brain injury, for which conventional treatments show limited efficacy. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has emerged as a promising intervention. However, existing evidence remains heterogeneous, necessitating a systematic integration of randomized controlled trials (RCTs) to clarify its therapeutic benefits. Pharmacological options such as amantadine remain limited, and outcomes often vary by etiology (e.g., traumatic vs. hypoxic–ischemic injury), underscoring the need for neuromodulatory approaches such as rTMS.

Methods

Following the PRISMA 2020 guidelines, we systematically searched PubMed, Embase, Cochrane Library, and other databases for articles published up to July 2025. RCTs involving DoC patients receiving rTMS (targeting the dorsolateral prefrontal cortex, DLPFC) compared to sham stimulation, with changes in Coma Recovery Scale-Revised (CRS-R) scores as the outcome, were included. Methodological quality was assessed using the Cochrane RoB 2.0 tool. Statistical analyses were performed in R with the ‘meta’ package, using standardized mean difference (SMD) and 95% confidence intervals (CI) to estimate effect sizes. Sensitivity analysis was conducted via the leave-one-out method, and publication bias was evaluated using funnel plots.

Results

Six RCTs comprising 274 DoC patients were included. Meta-analysis indicated that rTMS did not significantly improve post-intervention CRS-R total scores (SMD = 1.31, 95% CI –0.41 to 2.76). However, rTMS significantly increased the change in CRS-R scores (ΔCRS-R, SMD = 1.33, 95% CI 0.51–2.15). Subgroup analysis revealed that both 10 Hz (SMD = 1.46, 95% CI 0.14–2.78) and 20 Hz (SMD = 1.10, 95% CI 0.71–1.50) stimulation frequencies were effective, with no significant difference between them (χ2 = 0.26, p = 0.611). Sensitivity analysis identified the study by He et al. (2021) as a major source of heterogeneity. After its exclusion, the effect size for CRS-R total scores reached statistical significance (SMD = 0.63, 95% CI 0.29–0.97). Funnel plots suggested the presence of publication bias, which was markedly reduced after excluding the outlier study.

Conclusion

rTMS targeting the DLPFC can significantly promote recovery of consciousness in patients with DoC, with both 10 Hz and 20 Hz frequencies demonstrating clinical potential. Future large-sample, standardized RCTs are warranted to reduce heterogeneity and identify biomarkers for predicting treatment response, thereby facilitating the precision application of rTMS in DoC.