Multisensory BCI promotes motor recovery via high-order network-mediated interhemispheric integration in chronic stroke

BACKGROUND: Chronic stroke patients often experience persistent motor impairments, and current rehabilitation therapies rarely achieve substantial functional recovery. Sensory feedback during movement plays a pivotal role in driving neuroplasticity. This study introduces a novel multi-modal sensory feedback brain-computer interface (Multi-FDBK-BCI) system that integrates proprioceptive, tactile, and visual stimuli into motor imagery-based training. We aimed to explore the potential therapeutic efficacy and elucidate its neural mechanisms underlying motor recovery. METHODS: Thirty-nine chronic stroke patients were randomized to either the Multi-FDBK-BCI group (n = 20) or the conventional motor imagery therapy group (n = 19). Motor recovery was assessed using the Fugl-Meyer Assessment (primary outcome), Motor Status Scale, Action Research Arm Test, and surface electromyography. Functional MRI was used to examine brain activation patterns during upper limb tasks, while Granger causality analysis and machine learning evaluated inter-regional connectivity changes and their predictive value for recovery. RESULTS: Multi-FDBK-BCI training led to significantly greater motor recovery compared to conventional therapy. Functional MRI revealed enhanced activation of high-order transmodal networks-including the default mode, dorsal/ventral attention, and frontoparietal networks-during paralyzed limb movement, with activation strength positively correlated with motor improvement. Granger causality analysis identified a distinct information flow pattern: signals from the lesioned motor cortex were relayed through transmodal networks to the intact motor cortex, promoting interhemispheric communication. These functional connectivity changes not only supported motor recovery but also served as robust predictors of therapeutic outcomes. CONCLUSIONS: Our findings highlight the Multi-FDBK-BCI system as a promising strategy for chronic stroke rehabilitation, leveraging activity-dependent neuroplasticity within high-order transmodal networks. This multi-modal approach holds significant potential for patients with limited recovery options and sheds new light on the neural drivers of motor restoration, warranting further investigation in clinical neurorehabilitation. TRIAL REGISTRATION: All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (ChiCTR-ONC-17010739, registered 26 February 2017, starting from 10 January 2017).