Integrating Non-Invasive Brain Stimulation With Post-Stroke Rehabilitation: A Systematized Review of Synergistic Neuroplasticity Based Interventions.

BACKGROUND AND PURPOSE: Physiotherapy promotes experience-dependent neuroplasticity after stroke; however, recovery often plateaus despite intensive training. Non-invasive brain stimulation (NIBS) may enhance cortical excitability and increase responsiveness to motor practice, but the extent of synergistic benefit remains unclear. This systematic review aimed to evaluate randomized controlled trials (RCTs) integrating physiotherapy with NIBS and to determine whether combined interventions improve motor, gait, hand, and cognitive outcomes compared with physiotherapy alone or sham stimulation.

METHODS

A PRISMA-guided search was conducted across six databases from inception to August 2025, identifying RCTs that combined physiotherapy with NIBS modalities including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), repetitive transcranial magnetic stimulation (rTMS), and transcranial spinal direct current stimulation (tsDCS). Risk of bias was assessed using the Cochrane RoB 2 tool and the PEDro scale. Owing to substantial heterogeneity, a meta-analysis was not feasible and findings were synthesized narratively.

RESULTS

Fifteen RCTs involving 440 participants were included. Combined NIBS-physiotherapy interventions produced heterogeneous but generally favorable improvements, with stronger effects observed when anodal tDCS was delivered concurrently with high-intensity, task-specific rehabilitation such as robotic therapy, modified constraint-induced movement therapy, or virtual-reality-based training. Gait-related improvements were more consistent in individuals with chronic stroke undergoing robot-assisted or treadmill-based training, whereas trials in subacute stroke reported mixed results. Multisite neuromodulation approaches, including combined cortical and spinal stimulation or peripheral nerve stimulation, have demonstrated promising but preliminary effects, and few studies have reported mechanistic neurophysiological biomarkers.

DISCUSSION: Overall, the findings indicate that NIBS is most effective when functioning as a cortical "primer" during intensive, task-specific physiotherapy, with benefits influenced by stroke chronicity, behavioral context, and stimulation parameters. Future studies should prioritize standardized protocols, mechanistic biomarkers, and stratified trial designs to optimize clinical translation.