Non-invasive brain stimulation techniques for the improvement of upper limb motor function and performance in activities of daily living after stroke: a systematic review and network meta-analysis

Objective: To compare the efficacy of non-invasive brain stimulation (NiBS) such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcutaneous vagus nerve stimulation (taVNS) in upper limb stroke rehabilitation. Data sources: PubMed, Web of Science, and Cochrane databases were searched from January 2010 to June 2022. Data selection: Randomized controlled trials (RCT's) assessing the effects of "tDCS", "rTMS", "TBS", or "taVNS" on upper limb motor function and performance in activities of daily livings (ADLs) after stroke. Data extraction: Data were extracted by 2 independent reviewers. Risk of bias were was evaluated with the Cochrane Risk of Bias tool. Data synthesis: 87 RCTs with 3750 participants were included. Pairwise meta-analysis showed that all NiBS except continuous TBS (cTBS) and cathodal tDCS were significantly more efficacious than sham stimulation for motor function (Standard Meand Differerence (SMD) range 0.42 to 1.20) whereas taVNS, anodal tDCS, and both low and high frequency rTMS were significantly more efficacious than sham stimulation for ADLs (SMD range 0.54 to 0.99). NMA showed that taVNS was more effective than cTBS (SMD:1.00;95%CI(0.02 to 2.02), cathodal tDCS (SMD:1.07;95%CI(0.21 to 1.92) and Physical rehabilitation alone (SMD:1.46;95%CI(0.59 to 2.33)) for improving motor function. P-score found that taVNS is best ranked treatment in improving motor function (SMD: 1.20;95%CI(0.46 to 1.95) and ADLs (SMD:1.20;95%CI(0.45 to 1.94) after stroke. After taVNS, excitatory stimulation protocols (intermittent TBS, anodal tDCS and HF-rTMS) are most effective in improving motor function and ADLs after acute/sub-acute (SMD range 0.53 to 1.63) and chronic stroke (SMD range 0.39 to 1.16). Conclusions: Evidence suggests that excitatory stimulation protocols are the most promising intervention in improving upper limb motor function and performance in ADLs. taVNS appeared to be a promising intervention for stroke patients, but further large RCTs are required to confirm its relative superiority.