Transcranial Direct Current Stimulation In Hand Rehabilitation After Chronic Stroke:A FMRI Study

ObjectiveThe first objective of this study is to confirm the effects of dual transcranial direct current stimulation (tDCS) combined with functional electric therapy (FET) on chronic stroke patients with illness duration more than six months and severe hand dysfunction. The second objective is, using the resting-state functional magnetic resonance imaging (Rs-fMRI), to investigate the functional reorganization of resting-state networks (RSNs) for chronic stroke patients following tDCS intervention. Finally, we can insight into the recovery mechanism of tDCS on the hand impairement of chronic stroke patients by these clinical and neurophysiological findings, and further provide evidence-based stimulation programs.MethodsTotally 38 stroke patients from the Shanghai Third Rehabilitation Hospital and the public recruitment, who meet the eligible criteria were enrolled and randomely allocated into the experiment group (dual tDCS+FET) and the control group (sham tDCS+FET) by the central telephone method. And only 30 patients completed all of the data collection at the end of the project,15 cases in each group. The routine rehabilitation therapy was not restricted to both groups of patients, but shall be recorded in the basic information. Particapants in the experiment group received 20 minutes dual tDCS and 60 minutes FET, while participants in the control group received 20 minutes sham tDCS and 60 minutes FET. The anodal tDCS was placed on the affected primary motor cortex and cathodal tDCS was placed on the unaffected primary motor cortex, and all of the treatments were conducted once a day,5 days a week and totally 4 weeks. The clinical evaluations [including the modified Fugl-Meyer assessment of upper extremity (mFMA-UE), modified Ashworth Scale (MAS), and Broetz Hand Function Test (BHFT)], as well as Rs-fMRI scans were examined for all patients before and after 4 weeks of intervention.Results(1) Before treatment, there were no significant differences between groups in general data, mFMA-UE, MAS, and BHFT scores (P>0.05). For the spontaneous recovery stage before treatment, the first evaluation scores of the mFMA-UE and MAS in both groups compared with the second ones were also not significant (P>0.05).(2) After the 4 weeks intervention, all measurements (including the mFMA-UE, MAS, and BHFT scores) in both groups were significantly improved than those before treatment (P<0.01).(3) After the 4 weeks intervention, all measurements (including the mFMA-UE, MAS, as well as BHFT scores) between groups were no significant differences (P>0.05), but the improved scores of mFMA-UE and BHFT in the treatment group significantly exceeded those in the control group (P<0.05), and these findings were not replicated by the comparison of improved MAS scores between groups (P>0.05).(4) All of the 30 patients in both groups (15 cases in each group) completed the two Rs-fMRI scans before and after intervention. The functional connectivity (FC) analysis within RSNs found that the experiment group showed increased FC in the left (left side means lesion side) middle frontal gyrus and right precuneus within left sensorimotor network (1SMN) as well as bilateral cerebellum posterior lobe within dosal sensorimotor network (dSMN), while the control group showed increased FC in the left inferior parietal lobe within ventral sensorimotor network (vSMN) and in the left inferior frontal lobe within sensorimotor network (SMN), and decreased FC in the right lingual gyrus within SMN also be found. The FC analysis between RSNs found that the 1SMN showed increased FC with cerebellum network (CN) and decreased FC with executive network (ECN) in the experiment group, while the right sensorimotor network (rSMN) showed decreased FC with 1SMN and dSMN as well as increased FC with vSMN in the control group.(5) After the 4 weeks intervention, the increased FC value of left middle frontal gyrus was positively correlated with the improved mFMA-UE scores in the experiment group (r=0.54, P=0.04). Also, the FC in the left cerebellum posterior lobe of all stroke patients before treatment was negatively correlated with the improved mFMA-UE scores (r=-0.43, P=0.02), while the FC between 1SMN and rSMN before treatment was positively correlated with the improved BHFT socres (r=0.51, P<0.01).Conclusions1 Both the dual tDCS combined with FET and the single FET can improve the hand function of patients with severe chronic stroke, and dual tDCS combined with FET showed the synergistic effects in promoting the hand function recovery following chronic stroke.2 The dual tDCS combined with FET not only can modulate the FC within 1SMN and dSMN for chronic stroke patients with severe hand dysfunction, but also can modulate the FC between 1SMN with CN and ECN. These findings may be the underlying neural mechanism of dual tDCS combined with FET improving the upper extremity and hand function in chronic stroke patients.3 The increased FC in left middle frontal gyrus induced by dual tDCS combined with FET contribute to the hand function recovery of chronic stroke patients, and the more FC increased in left middle frontal gyrus, the more improvement of mFMA-UE scores in the experiment group patients.