Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei City, Taiwan.
Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei City, 11217, Taiwan.
J Neuroeng Rehabil. 2023 Feb 27;20(1):27. doi: 10.1186/s12984-023-01153-4.
Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients.
We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2-56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke.
Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01).
Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation.
This study is registered with ClinicalTrials.gov: (ID: NCT02731508).
双侧经颅直流电刺激（tDCS）刺激初级运动皮层（M1）可同时调节皮质脊髓兴奋性和大脑两半球间的相互作用。然而，tDCS 如何影响亚急性脑卒中的恢复仍不清楚。我们研究了双侧 tDCS 对亚急性脑卒中患者运动功能恢复的影响。
我们招募了首次皮质下区域缺血性脑卒中且基线 Fugl-Meyer 上肢评估（FMA-UE）评分 2-56 分中度至重度的亚急性期住院患者。患者在脑卒中后 14-28 天内，采用盲法、1:1 随机分配（真刺激组 n=13，假刺激组 n=14），接受双侧 tDCS（同侧 M1 阳极和对侧 M1 阴极，20min，2mA），每天两次，在两周内共 20 次治疗。根据组间皮质脊髓束的完整性将患者分层。主要疗效指标为 FMA-UE 评分较基线的变化（应答者定义为增加≥10）。次要观察指标包括干预后和脑卒中后 3 个月时动作研究上肢测试（ARAT）、FMA-下肢（FMA-LE）和目标区域静息状态功能磁共振成像（FC）的变化。
27 名参与者完成了研究，无明显不良反应。19 名患者（70%）的患侧前臂无记录到运动诱发电位（MEP 阴性）。与假刺激组相比，真刺激组在干预后 FMA-UE 改善更明显（p<0.01，效应量 η=0.211；应答率：77% vs. 36%，p=0.031），且该改善可持续至脑卒中后 3 个月（p<0.01），但 ARAT 无显著改善。有趣的是，在 MEP 阴性亚组分析中，FMA-UE 的改善仍然存在，但延迟。此外，真刺激组的 FMA-LE 改善直到脑卒中后 3 个月才显著大于假刺激组（p<0.01）。我们发现，真刺激组干预后个体 FMA-UE 的改善与目标皮质内的双侧半球内 FC 强度有关，而假刺激组干预后的改善与皮质脊髓束损伤后主要患侧 FC 的改变有关（p<0.01）。
任务导向训练时的双侧 tDCS 可能促进亚急性脑卒中患者的运动功能恢复，即使皮质脊髓束完整性受损。进一步的研究需要评估 tDCS 的疗效和网络特异性神经调节。
本研究在 ClinicalTrials.gov 注册（注册号：NCT02731508）。
