Behavioral effects in disorders of consciousness following transcranial direct current stimulation: A systematic review and individual patient data meta-analysis of randomized clinical trials

BACKGROUND: In patients with Disorders of Consciousness (DoC), recent evidence suggests that transcranial direct current stimulation (tDCS) can be a promising intervention for them. However, there has been little agreement on the treatment effect and the optimal treatment strategy for the tDCS in patients with DoC. OBJECTIVE: In this meta-analysis of individual patient data (IPD), we assess whether tDCS could improve DoC patients' behavioral performance. We also determine whether these treatment effects could be modified by patient characteristics or tDCS protocol. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials until 7 April 2022 using the terms “persistent vegetative state,” “minimally conscious state,” “disorder of consciousness,” or “unresponsive wakefulness syndrome,” and “transcranial direct current stimulation” to identify Randomized Controlled Trials (RCTs) in English-language publications. Studies were eligible for inclusion if they reported pre- and post-tDCS Coma Recovery Scale-Revised (CRS-R) scores. From the included studies, patients who had incomplete data were excluded. We performed a meta-analysis to assess the treatment effect of the tDCS compared with sham control. Additionally, various subgroup analyses were performed to determine whether specific patient characteristics could modify the treatment effect and to find out the optimal tDCS protocol. RESULTS: We identified 145 papers, but eventually eight trials (including 181 patients) were included in the analysis, and one individual data were excluded because of incomplete data. Our meta-analysis demonstrated a mean difference change in the CRS-R score of 0.89 (95% CI, 0.17–1.61) between tDCS and sham-control, favoring tDCS. The subgroup analysis showed that patients who were male or with a minimally conscious state (MCS) diagnosis were associated with a greater improvement in CRS-R score. We also found that patients who underwent five or more sessions of tDCS protocol had a better treatment effect than just one session. CONCLUSION: The result shows that tDCS can improve the behavioral performance of DoC patients. The heterogeneity of the treatment effect existed within the patients' baseline conditions and the stimulation protocol. More explorative studies on the optimal tDCS protocol and the most beneficial patient group based on the mechanism of tDCS are required in the future. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022331241.