Brain–computer interface (BCI)-guided robot-assisted upper-limb training has been increasingly applied to stroke rehabilitation. However, the induced long-term neuroplasticity modulation still needs to be further characterized. This study investigated the functional reorganization and its structural base after BCI-guided robot-assisted training using resting-state fMRI, task-based fMRI, and diffusion tensor imaging (DTI) data. The clinical improvement and the neurological changes before, immediately after, and six months after 20-session BCI-guided robot hand training were explored in 14 chronic stroke subjects. The structural base of the induced functional reorganization and motor improvement were also investigated using DTI. Repeated measure ANOVA indicated long-term motor improvement was found (F[2, 26] = 6.367, p = 0.006). Significantly modulated functional connectivity (FC) was observed between ipsilesional motor regions (M1 and SMA) and some contralesional areas (SMA, P Md, SPL) in the seed-based analysis. Modulated FC with ipsilesional M1 was significantly correlated with motor function improvement (r = 0.6455, p = 0.0276). Besides, increased interhemispheric FC among the sensorimotor area from resting-state data and increased laterality index from task-based data together indicated the re-balance of the two hemispheres during the recovery. Multiple linear regression models suggested that both motor function improvement and the functional change between ipsilesional M1 and contralesional premotor area were significantly associated with the ipsilesional corticospinal tract integrity. The results in the current study provided solid support for stroke recovery mechanism in terms of interhemispheric interaction and its structural substrates, which could further enhance the understanding of BCI training in stroke rehabilitation. This- study was registered at https://clinicaltrials.gov (NCT02323061).
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