Optimizing non-invasive vagus nerve stimulation for treatment in stroke

Stroke remains a leading cause of long-term disability worldwide. There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery. Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke. However, previously published research has only investigated a narrow range of stimulation settings and indications. In this review, we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials. We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke, highlighting their indications, parameter settings, scope, and limitations. We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation, focusing on critical aspects such as stimulation settings, target groups, biomarkers, and integration with rehabilitation interventions.