Effectiveness on level of consciousness of non-invasive neuromodulation therapy in patients with disorders of consciousness: a systematic review and meta-analysis

Abstract

BackgroundDisorders of consciousness (DoC) commonly occurs secondary to severe neurological injury. A considerable volume of research has explored the effectiveness of different non-invasive neuromodulation therapy (NINT) on awaking therapy, however, equivocal findings were reported.ObjectiveThe aim of this study was to systematically investigate the effectiveness on level of consciousness of different NINT in patients with DoC and explore optimal stimulation parameters and characteristics of patients.MethodsPubMed, Embase, Web of Science, Scopus, and Cochrane central register of controlled trials were searched from their inception through November 2022. Randomized controlled trials, that investigated effectiveness on level of consciousness of NINT, were included. Mean difference (MD) with 95% confidence interval (CI) was evaluated as effect size. Risk of bias was assessed with revised Cochrane risk-of-bias tool.ResultsA total of 15 randomized controlled trials with 345 patients were included. Meta-analysis was performed on 13 out of 15 reviewed trials indicating that transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS), and median nerve stimulation (MNS) all had a small but significant effect (MD 0.71 [95% CI 0.28, 1.13]; MD 1.51 [95% CI 0.87, 2.15]; MD 3.20 [95%CI: 1.45, 4.96]) on level of consciousness. Subgroup analyses revealed that patients with traumatic brain injury, higher initial level of consciousness (minimally conscious state), and shorter duration of prolonged DoC (subacute phase of DoC) reserved better awaking ability after tDCS. TMS also showed encouraging awaking effect when stimulation was applied on dorsolateral prefrontal cortex in patients with prolonged DoC.ConclusiontDCS and TMS appear to be effective interventions for improving level of consciousness of patients with prolonged DoC. Subgroup analyses identified the key parameters required to enhance the effects of tDCS and TMS on level of consciousness. Etiology of DoC, initial level of consciousness, and phase of DoC could act as significant characteristics of patients related to the effectiveness of tDCS. Stimulation site could act as significant stimulation parameter related to the effectiveness of TMS. There is insufficient evidence to support the use of MNS in clinical practice to improve level of consciousness in patients with coma.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337780, identifier: CRD42022337780.

Transcranial direct current stimulation modulates primate brain dynamics across states of consciousness.

“…From another clinical perspective, our results showing that 2 mA anodal PFC tDCS can positively influence the dynamic signatures of consciousness during anesthesia, are also consistent with the beneficial effects of such stimulation reported in DOCs patients (e.g., (Thibaut et al 2014;Angelakis et al 2014)). For instance, recent meta-analyses have concluded that tDCS is more effective in improving the level of consciousness in patients with a minimally conscious state (MCS) than in those with an unresponsive wakefulness syndrome (UWS), which is a more severe form of this medical condition (Xu et al 2022;Liu et al 2023). Our results support the efficacy of tDCS in improving consciousness markers in patients with DOCs, particularly in the least severely affected patients, and encourage the design of new clinical trials to investigate the effects of higher stimulation intensities.…”

Research hotspots and frontiers of neuromodulation techniques in disorders of consciousness: a bibliometric analysis

“…In the invasive brain stimulation, only Schiff et al demonstrated the efficacy of DBS in this particular patient through strictly design (Schiff et al, 2007). On the contrary, recent systematic review showed that NINT appeared to be effective interventions for improving MCS patients (Feng et al, 2020;Liu et al, 2023). In particular, tDCS has been shown through well-designed studies to have a limited capacity for enhancing functional recovery (Thibaut et al, 2014;Martens et al, 2018).…”

“…Among non-invasive methods, transcranial direct current stimulation (tDCS) ( Zaninotto et al, 2019 ), transcranial magnetic stimulation (TMS) ( O’Neal et al, 2021 ), Transcutaneous auricular vagus nerve stimulation (taVNS) ( Hakon et al, 2020 ), and median nerve stimulation (MNS) ( Feller et al, 2021 ) have been widely adopted and used in clinical samples. In a series of therapeutic methods for promoting rehabilitation, neuromodulation technology has a direct or indirect regulatory effect on functional connectivity between different brain regions by regulating cortical excitability and neural plasticity ( Feng et al, 2020 ; Liu et al, 2023 ). Over the past decade, the observed surge in publications clearly indicates that neuromodulation technology has been established as valuable tools for studying DOC.…”