A systematic review and network meta-analysis of neuromodulation techniques for promoting upper limb motor function after stroke

Abstract

OBJECTIVE: This study aimed to systematically compare the efficacy and safety of various neuromodulation techniques for upper limb motor function recovery after stroke, and to rank the relative advantages of different interventions through a network meta-analysis, thereby providing evidence-based guidance for clinical rehabilitation. METHODS: A comprehensive literature search was conducted in CNKI, WanFang, VIP, CBM, PubMed, EMbase, Web of Science, and Cochrane Library from inception to August 2025. Randomized controlled trials investigating different neuromodulation techniques for post-stroke upper limb motor impairment were included. Control group received sham stimulation or conventional rehabilitation, while trial group received additional neuromodulation therapies. The methodological quality of included studies was assessed using the Cochrane Risk of Bias Tool. Network meta-analyses were performed using Stata 16.0 and RevMan 5.4 software. RESULTS: A total of 51 randomized controlled trials were included, covering 12 neuromodulation stimulation modalities. Network meta-analysis results showed that compared with conventional treatment, high-frequency repetitive transcranial magnetic stimulation (MD=11.50, 95%CI: 6.83-16.16, P < 0.05) was most effective in improving basic upper limb motor function recovery; continuous theta burst stimulation (MD=12.10, 95%CI: 44.99-19.21, P < 0.05; MD=9.60, 95%CI: 1.32-17.88, P < 0.05) was most effective in improving the practicality and dexterity of upper limb function; and cathodal transcranial direct current stimulation (MD=15.40, 95%CI: 0.03-30.77, P < 0.05; MD=-0.83, 95%CI: -1.64 to -0.03, P < 0.05) was most effective in improving daily living activity limitations or with obvious spasticity. CONCLUSION: When the goal is to promote basic upper limb motor function recovery, high-frequency repetitive transcranial magnetic stimulation is most effective; for improving the practicality and dexterity of upper limb function, continuous theta burst stimulation is most effective; and for patients with impaired daily living ability accompanied by obvious spasticity, cathodal transcranial direct current stimulation is most effective.

1. Introduction

Stroke is one of the most significant public health burdens globally, consistently ranking among the leading causes of death and disability. Over 50% of stroke survivors experience upper limb motor dysfunction, which not only reduces their independence in daily activities but also increases family caregiving pressure and socioeconomic burden. Although traditional rehabilitation methods (such as biofeedback, neurodevelopmental therapy, and constraint-induced movement therapy) can induce neuroplasticity by enhancing sensorimotor input, their efficiency in modulating the reorganization of damaged motor networks is limited, making it difficult to meet the clinical needs for fine motor recovery. Combined interventions have become a direction of interest.

Neuromodulation techniques, as a class of central-directed interventions based on neuroplasticity theory, act on the central nervous system through non-invasive or minimally invasive methods, modulating cortical excitability, interhemispheric functional balance, and brain network connectivity, providing a new direction for upper limb functional rehabilitation after stroke. This study, considering clinical application frequency, the number of existing randomized controlled trials, and the relevance of outcome indicators, ultimately included 12 mainstream neuromodulation techniques for analysis, including repetitive transcranial magnetic stimulation (rTMS, including low-frequency, high-frequency, and theta burst stimulation modes), transcranial direct current stimulation (tDCS, including anodal, cathodal, bilateral, and high-definition subtypes), brain-computer interface (BCI), and transcutaneous auricular vagus nerve stimulation (taVNS). Independent studies have shown that these techniques combined with traditional rehabilitation can promote upper limb motor function recovery by enhancing motor cortex excitability and optimizing neural network synergy, but existing evidence has significant limitations.

Although systematic reviews and meta-analyses by Ahmed et al. have suggested that rTMS and tDCS are generally beneficial, they did not subdivide key parameters such as frequency and polarity. Most studies have focused on a single technique, lacking a horizontal comparison framework across multiple techniques, and failing to form an evidence chain from efficacy ranking to clinical selection. Given the highly refined functional distribution of the upper limb in the cerebral cortex, its functional reconstruction requires precise matching of intervention protocols, and current research cannot meet the clinical needs for goal-specific and individualized rehabilitation. This study, through network meta-analysis, synthesizes evidence from multiple neuromodulation techniques under a unified methodological framework, systematically comparing the relative effects of different strategies on upper limb functional recovery after stroke, providing interpretable and rankable evidence for precise clinical rehabilitation.