Brain computer interface (BCI)-based training is promising for the treatment of stroke patients with upper limb (UL) paralysis. However, most stroke patients receive comprehensive treatment that not only includes BCI, but also routine training. The purpose of this study was to investigate the topological alterations in brain functional networks following comprehensive treatment, including BCI training, in the subacute stage of stroke. Twenty-five hospitalized subacute stroke patients with moderate to severe UL paralysis were assigned to one of two groups: 4-week comprehensive treatment, including routine and BCI training (BCI group, BG, n = 14) and 4-week routine training without BCI support (control group, CG, n = 11). Functional UL assessments were performed before and after training, including, Fugl-Meyer Assessment-UL (FMA-UL), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). Neuroimaging assessment of functional connectivity (FC) in the BG was performed by resting state functional magnetic resonance imaging. After training, as compared with baseline, all clinical assessments (FMA-UL, ARAT, and WMFT) improved significantly (p < 0.05) in both groups. Meanwhile, better functional improvements were observed in FMA-UL (p < 0.05), ARAT (p < 0.05), and WMFT (p < 0.05) in the BG. Meanwhile, FC of the BG increased across the whole brain, including the temporal, parietal, and occipital lobes and subcortical regions. More importantly, increased inter-hemispheric FC between the somatosensory association cortex and putamen was strongly positively associated with UL motor function after training. Our findings demonstrate that comprehensive rehabilitation, including BCI training, can enhance UL motor function better than routine training for subacute stroke patients. The reorganization of brain functional networks topology in subacute stroke patients allows for increased coordination between the Wu et al.Clinical and rs-fMRI Study multi-sensory and motor-related cortex and the extrapyramidal system. Future long-term, longitudinal, controlled neuroimaging studies are needed to assess the effectiveness of BCI training as an approach to promote brain plasticity during the subacute stage of stroke.
