1 The University of Queensland, Centre for Clinical Research, Brisbane, 4029, Australia 2 Charité University Medicine, Department of Neurology, NeuroCure Clinical Research Centre, and Centre for Stroke Research 10117 Berlin, Germany
2 Charité University Medicine, Department of Neurology, NeuroCure Clinical Research Centre, and Centre for Stroke Research 10117 Berlin, Germany.
Brain. 2016 Apr;139(Pt 4):1152-63. doi: 10.1093/brain/aww002. Epub 2016 Feb 16.
Transcranial direct current stimulation has shown promise to improve recovery in patients with post-stroke aphasia, but previous studies have only assessed stimulation effects on impairment parameters, and evidence for long-term maintenance of transcranial direct current stimulation effects from randomized, controlled trials is lacking. Moreover, due to the variability of lesions and functional language network reorganization after stroke, recent studies have used advanced functional imaging or current modelling to determine optimal stimulation sites in individual patients. However, such approaches are expensive, time consuming and may not be feasible outside of specialized research centres, which complicates incorporation of transcranial direct current stimulation in day-to-day clinical practice. Stimulation of an ancillary system that is functionally connected to the residual language network, namely the primary motor system, would be more easily applicable, but effectiveness of such an approach has not been explored systematically. We conducted a randomized, parallel group, sham-controlled, double-blind clinical trial and 26 patients with chronic aphasia received a highly intensive naming therapy over 2 weeks (8 days, 2 × 1.5 h/day). Concurrently, anodal-transcranial direct current stimulation was administered to the left primary motor cortex twice daily at the beginning of each training session. Naming ability for trained items (n = 60 pictures that could not be named during repeated baseline assessments), transfer to untrained items (n = 284 pictures) and generalization to everyday communication were assessed immediately post-intervention and 6 months later. Naming ability for trained items was significantly improved immediately after the end of the intervention in both the anodal (Cohen's d = 3.67) and sham-transcranial direct current stimulation groups (d = 2.10), with a trend for larger gains in the anodal-transcranial direct current stimulation group (d = 0.71). Treatment effects for trained items were significantly better maintained in the anodal-transcranial direct current stimulation group 6 months later (d = 1.19). Transfer to untrained items was significantly larger in the anodal-transcranial direct current stimulation group after the training (d = 1.49) and during the 6 month follow-up assessment (d = 3.12). Transfer effects were only maintained in the anodal-transcranial direct current stimulation group. Functional communication was significantly more improved in the anodal-transcranial direct current stimulation group at both time points compared to patients treated with sham-transcranial direct current stimulation (d = 0.75-0.99). Our results provide the first evidence from a randomized, controlled trial that transcranial direct current stimulation can improve both function and activity-related outcomes in chronic aphasia, with medium to large effect sizes, and that these effects are maintained over extended periods of time. These effects were achieved with an easy-to-implement and thus clinically feasible motor-cortex montage that may represent a promising 'backdoor' approach to improve language recovery after stroke.
经颅直流电刺激已显示出改善卒中后失语症患者康复的潜力,但之前的研究仅评估了刺激对损伤参数的影响,而且缺乏随机对照试验中经颅直流电刺激效果长期维持的证据。此外,由于卒中后病变和功能语言网络的可变性,最近的研究使用先进的功能成像或电流建模来确定个体患者的最佳刺激部位。然而,这些方法昂贵、耗时,并且在专门的研究中心之外可能不可行,这使得经颅直流电刺激难以纳入日常临床实践。刺激与残留语言网络功能连接的辅助系统,即初级运动系统,将更容易实现,但这种方法的有效性尚未得到系统探索。我们进行了一项随机、平行组、假刺激对照、双盲临床试验,26 名慢性失语症患者接受了为期 2 周的高强度命名治疗(8 天,每天 2 次,每次 1.5 小时)。同时,在每次训练开始时,对左侧初级运动皮层进行每日两次的阳极经颅直流电刺激。对训练项目(n = 60 张在重复基线评估中无法命名的图片)的命名能力、对未训练项目(n = 284 张图片)的转移能力以及对日常交流的泛化能力进行评估,在干预结束后立即和 6 个月后进行评估。阳极(Cohen's d = 3.67)和假刺激经颅直流电刺激组(d = 2.10)的训练项目命名能力在干预结束后立即显著提高,阳极刺激组的增益趋势更大(d = 0.71)。6 个月后,阳极经颅直流电刺激组的训练项目治疗效果保持更好(d = 1.19)。在训练后(d = 1.49)和 6 个月随访评估时(d = 3.12),阳极经颅直流电刺激组对未训练项目的转移明显更大。只有阳极经颅直流电刺激组的转移效果得以维持。在这两个时间点,与接受假刺激经颅直流电刺激的患者相比,阳极经颅直流电刺激组的功能性交流均显著改善(d = 0.75-0.99)。我们的研究结果首次提供了来自随机对照试验的证据,表明经颅直流电刺激可以改善慢性失语症的功能和与活动相关的结果,其效果具有中等至较大的效应量,而且这些效果可以长时间维持。这些效果是通过一种易于实施的运动皮层刺激模式实现的,因此在临床上是可行的,这种模式可能代表了改善卒中后语言恢复的一种有前途的“后门”方法。