Abstract
Brain-computer interfaces (BCIs) are increasingly explored as tools for post-stroke neurorehabilitation. Motor imagery (MI)-based paradigms are widely used but may be difficult for some patients to perform reliably, motivating the exploration of alternative control strategies. This study presents a retrospective exploratory case series (n = 5) evaluating the feasibility and safety of a P300-based BCI paradigm designed to engage visuomotor transformation processes during upper limb rehabilitation. Two patients underwent rehabilitation using the P300-based paradigm, while three patients used an MI-based BCI within the same rehabilitation framework. In both conditions, BCI control was integrated with a robotic orthosis and an immersive virtual reality (VR) environment. BCI performance, neurophysiological responses (event-related potentials and event-related desynchronization), and clinical measures (Fugl-Meyer Assessment of the Upper Extremity, NIHSS) were assessed before and after a 10-session rehabilitation course. All participants were able to achieve BCI control above chance level. Across cases, changes in clinical scores and consistent neurophysiological patterns associated with task engagement were observed. No adverse events or clinically significant safety concerns were identified. These findings suggest that a P300-based BCI paradigm incorporating visuomotor transformation can be feasibly implemented within a VR-assisted robotic rehabilitation framework. Given the exploratory design, small sample size, and heterogeneity of the cohort, the results should be interpreted as hypothesis-generating. Further controlled studies are required to determine the clinical relevance and potential applications of this approach.