Enhancement of Cerebral Oxygenation by Lower-Limb Neuromuscular Electrical Stimulation in Stroke Survivors

PURPOSE: Stroke remains a leading cause of death and long-term disability with few non-pharmacological interventions available to enhance cerebral perfusion during recovery. Neuromuscular electrical stimulation (NMES) of the common peroneal nerve (CPN) may augment venous return and cardiac output via activation of the skeletal muscle pump and autonomic reflexes thereby supporting cerebral blood flow. This study aimed to evaluate the effects of low-frequency (1 Hz) CPN-NMES on cortical oxygenation in ischaemic stroke survivors and to mechanistically interpret these effects using cardiovascular computational modelling. METHODS: In the Phase 1 RETRAIN study (NCT06614400), eighteen individuals with ischaemic stroke underwent transcutaneous CPN-NMES delivered at 1 Hz (1 pulse per second) using a wearable device at graded stimulation intensities across three postures (supine, semi-supine, and sitting). Cortical oxygenation was continuously monitored using functional near-infrared spectroscopy (fNIRS). A lumped-parameter cardiovascular model was used to simulate NMES-induced changes in venous return, cardiac output, and systemic haemodynamics. Linear mixed-effects models analysed experimental data, with transcutaneous carbon dioxide included as a covariate to account for cerebrovascular reactivity. RESULTS: CPN-NMES elicited significant, dose-dependent increases in cortical oxygenation. Effects were amplified in upright postures and in participants with larger infarct volumes (>5 cm). Computational modelling confirmed that 1 Hz CPN-NMES enhances venous return and cardiac output while maintaining haemodynamic stability. Sex-specific cardiovascular adaptations were observed with females demonstrating greater heart rate-mediated responses. CONCLUSION: Low-frequency CPN-NMES enhances cortical oxygenation in stroke survivors through posture-, lesion-, and sex-dependent cardiovascular mechanisms. Wearable CPN-NMES represents a promising, non-invasive adjunct to stroke rehabilitation that warrants further investigation in larger controlled trials.