rTMS and TBS Improve Unilateral Spatial Neglect Post-Stroke: Meta-Analysis of 425 Patients

BACKGROUND: Unilateral spatial neglect (USN) is one of the most common behavioral cognitive impairments after stroke, limiting functional activities and impairing daily life. Increasing evidence suggests that noninvasive brain stimulation (NIBS) holds a promising therapeutic potential in the field of post-stroke neglect rehabilitation, but its effect still needs to be systematically evaluated. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the effect of NIBS for the treatment of USN after stroke and to examine the effect of moderating variables (e.g., stroke phase, protocol type) on the effect sizes of NIBS treatment. METHODS: Systematically searched for randomized controlled trials (RCTs) or crossover RCTs on NIBS for the treatment of USN from four databases: PubMed, Embase, Web of Science and the Cochrane Library. The search period spanned from inception to May 1, 2025. Subgroup analysis was conducted based on the NIBS interventions (rTMS, TBS, tDCS and tACS). The primary outcomes included the line bisection test (LBT), star cancellation test (SCT), and catherine bergego scale (CBS). RESULTS: The results of 17 studies (425 patients) showed that different effects of various NIBS interventions (rTMS, TBS, tDCS and tACS) on USN outcomes: rTMS significantly reduced LBT (SMD = -1.82, P < 0.00001), SCT (SMD = -1.59, P < 0.00001), and CBS (MD = -2.76, P = 0.002); TBS significantly reduced SCT (SMD = -2.59, P = 0.03) and CBS (MD = -0.93, P < 0.0001); tDCS significantly reduced LBT (SMD = -0.60, P = 0.0009) and SCT (SMD = -0.60, P = 0.001); while tACS showed no significant difference compared to the control group in improving LBT (SMD = 0.04, P = 0.93) and SCT (SMD = -0.32, P = 0.49). Additionally, subgroup analyses showed that intervention timing and NIBS protocol type exerted moderating effects on treatment effect in USN patients. Intervention during the acute stroke phase may yield greater effect compared to those in the chronic phase (P < 0.00001). Excitatory NIBS protocols targeting the ipsilesional posterior parietal cortex (PPC) may yield greater therapeutic potential than inhibitory protocols applied to the contralesional PPC (P < 0.05). CONCLUSION: rTMS and TBS showed greater therapeutic potential than tDCS and tACS in reducing neglect severity and improving activities of daily living. In addition, modulating variables may potentially influence the therapeutic effect of NIBS intervention. Specifically, early intervention and excitatory NIBS protocols applied to the ipsilesional PPC for post-stroke USN patients may have greater therapeutic potential.