Stroke is the second-leading cause of death and the third-leading cause of disability worldwide1. Epidemiological studies indicate that approximately 80% of stroke survivors experience persistent upper extremity motor impairment during the acute phase2, resulting in substantial limitations in both physical functioning and social participation3. The recovery process is fundamentally mediated by intrinsic neuroplastic mechanisms, including both physiological and anatomical adaptations, which facilitate functional motor improvement4,5. Notably, these neuroplastic changes evolve through distinct temporal phases, with gradual synaptic reorganization emerging during the subacute period spanning days to weeks post-stroke.
Based on the principles of Hebbian plasticity, post-stroke motor recovery requires not only cortical motor control activation but also functional transmission of motor commands to muscle effectors, thereby engaging complete cortico-muscular pathways6. Brain-computer interfaces (BCIs) establish direct communication channels between users and computers, circumventing conventional neural pathways between the brain and muscles7. When utilized for motor neuromodulation, BCI systems facilitate activity-dependent plasticity by enabling users to concentrate on tasks that modulate specific neural signals8,9. Electroencephalography (EEG) has become the predominant modality for BCI systems due to its noninvasive nature, excellent temporal resolution, potential for user mobility, and cost-effectiveness10. EEG-based BCIs are broadly categorized into evoked and spontaneous systems11. Evoked systems rely on external stimuli (visual, auditory, or sensory) to elicit brain responses that the BCI system interprets to determine user intent12. In contrast, spontaneous BCIs operate without external stimuli, utilizing brain activity generated through mental processes11.Motor imagery (MI)-based BCIs represent a prominent example of spontaneous systems13. MI, the cognitive simulation of movement without physical execution, was developed based on neuroplasticity principles14. This approach offers particular advantages for stroke rehabilitation, enabling patients with severe motor impairments to engage in therapeutic interventions15. MI paradigms primarily encompass visual imagery (VI) and kinesthetic imagery (KI). VI involves the visualization of limb movement from either a first-person or third-person perspective16,17,18, while KI entails the mental simulation of the somatosensory experience associated with performing the movement19. Both modalities facilitate information processing and cortical activation, though distinct neural mechanisms20. While both VI and KI have demonstrated efficacy in BCI applications, empirical evidence suggests KI’s superior performance. Marchesotti et al.21 established a correlation between BCI proficiency and paradigm adaptability, demonstrating that users with higher BCI aptitude achieve better MI-EEG decoding accuracy with KI paradigms. These findings were corroborated by Toriyama et al.22, whose comparative studies revealed stronger event-related desynchronization patterns during KI, showing greater similarity to actual motor execution.
Noninvasive brain stimulation techniques have emerged as valuable tools for monitoring and modulating the excitability of intracortical neuronal circuits, with the capacity to induce lasting neurophysiological changes through prolonged cortical stimulation. Among these techniques, transcranial direct current stimulation (tDCS) has gained considerable attention for its neuromodulatory potential. tDCS delivers constant low-intensity direct current (1–2 mA) to targeted cortical regions, thereby modulating neuronal activity in the cerebral cortex23. The underlying mechanism involves the regulation of resting membrane potentials through modulation of sodium- and calcium-dependent channels, along with N-methyl-D-aspartate receptor activity24. Post-stroke neurophysiology is characterized by an imbalance in interhemispheric cortical activity, with the affected hemisphere exhibiting increased excitability and diminished local inhibitory circuit activity25. TDCS offers a targeted approach to address this imbalance: anodal stimulation induces neuronal depolarization to enhance cortical excitability, while cathodal stimulation promotes hyperpolarization to reduce excitability26. This polarity-specific modulation enables precise regulation of cortical excitability, potentially facilitating plastic reorganization within the sensorimotor network. Consequently, tDCS represents a promising therapeutic approach for improving upper limb function in subacute stroke patients through targeted neuromodulation.
This study aims to investigate the synergistic potential of combining anodal tDCS with BCI interventions for motor rehabilitation in subacute stroke patients. Previous research27 involving healthy participants demonstrated that the combination of anodal tDCS and BCI interventions induce significant neurophysiological changes. These changes include altered directed connectivity between frontal and parietal regions, and enhanced information flow between the premotor cortex and sensorimotor cortex during MI tasks. Importantly, these neurophysiological modifications were behaviorally relevant, correlating with improved task performance as evidenced by increased correct trials and reduced completion times. Building on these findings, recent studies have suggested that both KI-BCI and tDCS independently facilitate motor rehabilitation in stroke patients through cortical plasticity modulation28,29. The subacute phase of stroke recovery (14–180 days) represents a critical therapeutic window, characterized by approximately 90 days of enhanced synaptic plasticity that parallels the period of most rapid behavioral recovery25. Within this context, we hypothesized that: (1) both KI-BCI and tDCS would significantly improve upper limb function in subacute stroke patients, and (2) the combined intervention would demonstrate superior efficacy compared to either treatment alone. Furthermore, we aimed to elucidate the underlying neural mechanisms through quantitative EEG analysis.
To test these hypotheses, we conducted a three-armed randomized controlled trial comparing KI-BCI, tDCS, and their combination. The study specifically focused on the subacute phase to capitalize on the period of heightened neuroplasticity, while addressing the current uncertainty regarding the efficacy of combined tDCS-BCI interventions in clinical populations.
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