Comparative Efficacy of Noninvasive Neuromodulation in Patients with Disorders of Consciousness: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Objective: To evaluate the efficacy of various noninvasive neuromodulation in restoring consciousness in patients with disorders of consciousness (DoC) through a network meta-analysis and identify the optimal noninvasive neuromodulation strategies. Design: Systematic review and network meta-analysis. Methods: A comprehensive and systematic literature search was conducted for this study, encompassing several authoritative databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, and ClinicalTrials.gov. This study adhered to the PRISMA-Network Meta-Analysis guidelines and was registered with PROSPERO (CRD420251018090). Literature screening, data extraction, and bias assessment (using the PEDro scale) were performed independently by 2 reviewers. A Bayesian framework-based network meta-analysis was conducted using the GeMTC package in R. Treatment rankings were determined using the surface under the cumulative ranking curve. Results: A total of 41 studies were included, of which 19 were used for quantitative analysis. For Coma Recovery Scale-Revised (CRS-R), high frequencies-repetitive transcranial magnetic stimulation-primary motor cortex (HF-rTMS-M1) demonstrated the most pronounced effect (MD = 7.1; 95% CI = 2.6-11), followed by right median nerve electrical stimulation (RMNS) plus HF-rTMS-dorsolateral prefrontal cortex (DLPFC) (MD = 5.0; 95% CI = 2.6-7.5) and RMNS (MD = 3.0; 95% CI = 1.1-4.9). For Glasgow Coma Scale (GCS), subgroup analysis by etiology indicated that both HF-rTMS-DLPFC and HF-rTMS-M1 significantly improved CRS-R and GCS scores in patients with traumatic brain injury-related disorders of consciousness. The included studies generally demonstrated low risk of bias and the analysis model showed minimal heterogeneity ( I 2 < 5%), supporting the robustness of these findings. Conclusions: HF-rTMS-M1 and RMNS plus HF-rTMS-DLPFC, RMNS, HF-rTMS-DLPFC, and tDCS have shown positive signals in patients with DoC. The duration of the disorder and underlying etiology may influence the effectiveness of different noninvasive neuromodulation techniques in DoC. Given the marked heterogeneity of DoC and the limitations of the present study, these findings should be interpreted as hypothesis-generating observations rather than universally applicable conclusions. Further high-quality randomized controlled trials (RCTs) are warranted to provide robust evidence on the most suitable neuromodulation approaches for different DoC populations and to evaluate their long-term efficacy.