A Narrative Review on the Current Landscape of Invasive Neuromodulation for Poststroke Motor Recovery: Mechanisms, Challenges, and Future Directions.

Stroke is a leading cause of disability. Despite rehabilitation efforts, most survivors of stroke do not fully recover. Invasive neuromodulation has shown promise but has not yet become standard of care in poststroke rehabilitation. Given the inherent drawbacks of invasive modalities, a critical evaluation is warranted. This review examines invasive neuromodulation strategies for poststroke recovery, focusing on their mechanisms of action, clinical evidence, and technical challenges. A structured search was conducted using PubMed for studies from 2000 to 2025, with the terms ("Stroke"[MeSH] OR "Stroke Rehabilitation"[MeSH]) and ("Neurostimulation" OR "Invasive Electrical Stimulation" OR "Deep Brain Stimulation" OR "Epidural Stimulation" OR "Spinal Cord Stimulation" OR "Cortical Stimulation" OR "Cerebellar Stimulation"). Only human studies were included. Moreover, clinical trials from ClinicalTrials.gov and the European Union Clinical Trials Register were cross-referenced, and preclinical studies underpinning selected clinical trials were integrated. Vagal nerve stimulation has received Food and Drug Administration approval, whereas motor cortex stimulation, cerebellar stimulation, and spinal cord stimulation remain investigational. These methods aim to recruit residual motor networks and promote plasticity. However, narrow cohorts, variability in stroke location and timing, differences in rehabilitation intensity, and inconsistencies in outcome measures present significant challenges to achieving consistent and broadly applicable therapeutic outcomes across trials. Given the risks associated with invasive techniques, a deeper understanding of their mechanisms is essential to maximizing their therapeutic potential. Nevertheless, advances in electrode technology, adaptive stimulation, and multimodal approaches hold promise for optimizing the effectiveness of invasive neuromodulation and improving patient outcomes.