Efficacy of non-invasive brain stimulation for disorders of consciousness: a systematic review and meta-analysis

Abstract

Objective: The aim of this study is to evaluate the efficacy of non-invasive brain stimulation (NIBS) in patients with disorders of consciousness (DoC) and compare differences in efficacy between different stimulation modalities.

Methods: We searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for all studies published in English from inception to April 2023. Literature screening and quality assessment were performed independently by two investigators. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to evaluate the therapeutic effects of NIBS. The Cochrane Q test and I² statistic were used to evaluate heterogeneity between studies. Subgroup analysis was performed to identify the source of heterogeneity, and differences in efficacy between different stimulation modalities were compared by Bayesian analysis.

Results: A total of 17 studies with 377 DoC patients were included. NIBS significantly improved the state of consciousness in DoC patients when compared to sham stimulation (WMD: 0.81; 95% CI: 0.46, 1.17; I² = 78.2%, p = 0.000). When divided into subgroups according to stimulation modalities, the heterogeneity of each subgroup was significantly lower than before (I²: 0.00-30.4%, p >0.05); different stimulation modalities may be the main source of such heterogeneity. Bayesian analysis, based on different stimulation modalities, indicated that a patient's state of consciousness improved most significantly after repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Diagnosis-based subgroup analysis showed that NIBS significantly improved the state of consciousness in patients with a minimal consciousness state (WMD: 1.11; 95% CI: 0.37, 1.86) but not in patients with unresponsive wakefulness syndrome or a vegetative state (WMD: 0.31; 95% CI: -0.09, 0.71). Subgroup analysis based on observation time showed that single treatment did not improve the state of consciousness in DoC patients (WMD: 0.28; 95% CI: -0.27, 0.82) while multiple treatments could (WMD: 1.05; 95% CI: 0.49, 1.61). Furthermore, NIBS had long-term effects on DoC patients (WMD: 0.79; 95% CI: 0.08-1.49).

Conclusion: Available evidence suggests that the use of NIBS on patients with DoC is more effective than sham stimulation, and that rTMS of the left DLPFC may be the most prominent stimulation modality.

Keywords: disorders of consciousness (DOC); meta-analysis; non-invasive brain stimulation (NIBS); repetitive transcranial magnetic stimulation (rTMS); transcranial direct current stimulation (tDCS); transcranial random noise stimulation (tRNS).