Trans-cranial Direct Current Stimulation to Treat Aphasia: Phase II Trial

描述(由申请人提供)：中风是美国成年人残疾的主要原因。中风造成的最具破坏性的损害之一是失语症，这是一种由涉及大脑皮质语言区的左半球损伤引起的语言障碍。虽然相当多的研究工作集中在提高失语症的治疗效果上，但大多数患有失语症的慢性中风患者的康复有限。因此，提高失语症的治疗效果是非常重要的，因为它可以改善患者的沟通能力和生活质量。最近利用动物模型进行的研究表明，小电流经颅直流电刺激(TDC)可以局部增加脑源性神经营养因子(BDNF)的分泌，这是一种对诱导大脑可塑性至关重要的蛋白质。人类研究进一步证明了阳极tdcs(A-tdcs)对正常受试者学习的积极作用。我们首次在两项研究中展示了A-tDCs如何显著提高对慢性中风失语症患者的失调症(说出常见物体的能力受损)的行为治疗效果。基于这些发现以及我们旨在了解与失语症治疗相关的大脑可塑性的其他研究，我们建议进行一项第二阶段临床试验，以检验A-tDCs对慢性中风患者失范治疗结果的影响。该项目将包括一项双臂随机、前瞻性、双盲试验(主动与对照)，慢性稳定的中风患者将接受行为失语症治疗，同时接受A-TDC或Sham TDC(S-TDC)。因为失语是失语症的标志性损害，并且在所有失语症患者中都存在，无论严重程度或失语症类型，主要结果因素将是失范严重程度，定义为正确命名常见物体的能力。这项研究的长期目标是进行一项第三阶段试验，以确定A-tDCs是否显著增强了行为失语治疗的效果。如果A-tdcs被证明对失语症的治疗结果有积极作用，那么当A-tdcs与A-tdcs结合使用时，目前接受有限或没有治疗益处的患者可能会对治疗有反应。同样，对于在没有直接脑刺激的情况下对治疗反应积极的患者，A-tDCs可能会进一步提高治疗效果。

DESCRIPTION (provided by applicant): Stroke is the leading cause of adult disability in the United States. One of the most devastating impairments resulting from stroke is aphasia, a language impairment caused by left hemisphere damage involving cortical language areas. Although considerable research effort has focused on increasing aphasia treatment efficacy, most chronic stroke patients with aphasia experience limited recovery. Therefore, enhanced aphasia treatment outcome is of paramount interest as it may improve patients' communication ability and quality of life. Recent studies utilizing animal models suggest that low current transcranial direct current stimulation (tDCS) can locally increase the secretion of brain derived neurotrophic factor (BDNF), a protein that is crucial for induction of brain plasticity. Research i humans has further demonstrated the positive effect of anodal tDCS (A-tDCS) on learning in normal subjects. For the first time, we have shown in a pair of studies how A-tDCS can significantly enhance the effect of the behavioral treatment of anomia (impaired ability to name common objects) in patients with chronic stroke-induced aphasia. Capitalizing on these findings as well as our other research aimed at understanding brain plasticity associated with aphasia treatment, we propose to conduct a Phase II clinical trial to examine the effect of A-tDCS on anomia treatment outcome in patients with chronic stroke. This project will include a randomized, prospective, double-blind trial with two arms (active vs. control) wherein chronically stable stroke patients will receive behavioral aphasia treatment coupled with either A-tDCS or sham tDCS (S-tDCS). Because anomia is the hallmark impairment in aphasia and is present in all aphasic patients, regardless of severity or aphasia type, the primary outcome factor will be anomia severity, defined as the ability to correctly name common objects. The long-term goal of this research is to conduct a Phase III trial to determine if A-tDCS significantly enhances the effect of behavioral aphasia treatment. If the A-tDCS is proven to have a positive effect on aphasia treatment outcome, it is possible that patients who currently receive limited or no treatment benefit may respond to treatment when it is coupled with A-tDCS. Similarly, it is possible that A-tDCS may further boost the treatment effect for patients who respond positively to treatment in the absence of direct brain stimulation.