Multimodal therapeutic efficacy assessment of vagus nerve stimulation in stroke: integrated application of imaging, electrophysiological, and behavioral indicators

Stroke remains a leading cause of mortality and long-term disability worldwide, and conventional rehabilitation alone frequently results in incomplete functional recovery. This review aims to establish a mechanism-informed, clinically actionable framework for quantifying the therapeutic effects of vagus nerve stimulation after stroke across complementary modalities. We synthesize evidence spanning neuroanatomical principles, mechanistic pathways, and technological development, and organize outcome measures into an integrated triad of imaging, electrophysiological, and behavioral indicators. Across studies, imaging outcomes consistently associate stimulation with reduced infarct burden, improved blood-brain barrier integrity, and enhanced circuit remodeling, whereas electrophysiological measures capture autonomic rebalancing and neural stabilization, exemplified by increased high-frequency heart rate variability and lower low-/high-frequency ratios. Behavioral outcomes indicate clinically meaningful gains, including improvements on upper-limb motor scales (with invasive stimulation frequently associated with ≥8-point increases on the Fugl-Meyer Assessment-Upper Extremity) and reductions in post-stroke spasticity (with reported 30-40% decreases in the incidence of increased tone). Safety profiles are modality dependent: implanted systems may entail procedure- and stimulation-related adverse events that are generally manageable with parameter adjustment, whereas noninvasive approaches predominantly cause transient local discomfort with no reported fatal events. Collectively, multimodal assessment provides a rigorous "structure-electrophysiology-function-behavior" evidence chain to support precise parameter optimization, standardized implementation, and scalable translation of vagus nerve stimulation for stroke rehabilitation.