Transcranial Direct Current Stimulation and Aphasia Language Therapy

描述(申请人提供)：这项第一阶段的探索性研究评估了重复经颅直流电刺激(TDCS)结合强化言语语言治疗(SLT)的安全性和可行性，并收集了在不同极性条件下对慢性非流利性失语症患者的疗效的初步数据。通过对大脑皮层直接施加刺激来促进大脑可塑性已经在动物模型中进行了研究，结果令人振奋，并随后应用于中风后运动障碍的康复。应用于中风后的语言问题才刚刚出现，但结果表明，皮质刺激作为失语症康复的辅助策略具有潜在的作用。在现有的方法中，tDCS因其非侵入性应用、易于管理和相对较低的成本而具有最大的临床应用潜力。然而，在很长一段时间内(例如，在康复的几周期间)每天使用这种药物时，关于安全性的数据不足。此外，对于失语症患者在哪里进行最佳刺激的问题，以前还没有解决过，即在受损的左半球或完好的右半球进行阳极或阴极刺激。因此，这项研究的具体目的是评估1 mA tdcs(阳极、阴极或假刺激)在连续6周每周5天13分钟的刺激结合强化SLT时的安全性。此外，还评估和比较了每种刺激方式的疗效和神经生物学变化。12名患有重度或中-重度非流利性失语的患者被随机分为三组：左侧大脑半球正极TDC组；左侧大脑半球阴极TDC组；或假刺激组。刺激地点是通过观察、模仿、口头阅读和词汇生成的fMRI任务确定的，左侧前运动皮质激活在三个指示刺激地点的交叉图之一中。治疗包括1 mA tDCs(或假刺激)13分钟，同时进行言语-语言治疗(SLT)，然后再进行77分钟的SLT，总共90分钟的SLT。外语教学是通过计算机进行的，包括口语朗读和会话练习。主要终点是安全性，通过不良事件的数量或认知或语言能力下降的证据来衡量。主要的治疗结果指标是西方失语症成套测验失语商从治疗前到治疗后的变化，次要结果指标包括波士顿命名测试的变化分数，交际有效性指数，以及信息内容和速度的话语指标。神经生物学测量包括每个半球和感兴趣区域的激活总体积的变化，包括外侧运动前区(包括额叶下回的盖部)。TDC联合SLT可能是安全的，并可能导致改善结果，对失语症患者的成本和康复服务的提供具有重要影响。公共卫生相关性：失语症是中风的一种常见症状，对个人的日常功能活动和情绪健康有巨大影响。经颅直流电刺激(TDC)结合言语和语言治疗可能会改善结果，并对失语症患者的康复服务的成本和提供有重要影响。优化语言康复，提高失语症患者的生活质量，可能会促进他们重返社区和劳动力大军，从而降低社会的经济成本。

DESCRIPTION (provided by applicant): This Phase 1 exploratory study assesses the safety and feasibility of repeated transcranial direct current stimulation (tDCS) in combination with intensive speech-language treatment (SLT) and collects preliminary data about its efficacy under different polarity conditions in individuals with chronic nonfluent aphasia. Facilitating brain plasticity with the direct application of stimulation to the cerebral cortex has been studied in animal models with promising results and subsequently applied to the rehabilitation of motor deficits after stroke. Application to language problems after stroke is only emerging, but results suggest a potential role for cortical stimulation as an adjuvant strategy in aphasia rehabilitation. Of the methods available, tDCS has the greatest potential for clinical use in view of its non-invasive application, ease of administration and relative low cost. However, there is insufficient data regarding safety when it is applied daily over a prolonged period of time (e.g. during several weeks of rehabilitation). Furthermore, the question of where best to apply the stimulation for individuals with aphasia has not been previously addressed i.e. anodal or cathodal to the lesioned left hemisphere or to the intact right hemisphere. Accordingly, the specific aims of this study are to assess the safety of 1 mA tDCS (anodal, cathodal, or sham stimulation) when applied for 13 minutes, 5 days a week for 6 weeks in combination with intensive SLT. In addition, the therapeutic efficacy and neurobiological change associated with each mode of stimulation are assessed and compared. Twelve individuals with severe or moderately-severe nonfluent aphasia are randomized to one of three groups: anodal tDCS to the left hemisphere; cathodal tDCS to the left hemisphere; or sham stimulation. Site of stimulation is determined from fMRI tasks of observation, imitation, oral reading, and word generation with activation in left premotor cortex in one of three intersection maps indicating site of stimulation. Treatment includes 1 mA tDCS (or sham stimulation) for 13 minutes simultaneously with speech-language therapy (SLT), followed by an additional 77 minutes of SLT for a total of 90 minutes of SLT. SLT is provided via computer and involves oral reading of sentences and conversational practice. The primary endpoint is safety, measured by the number of adverse events or evidence of cognitive or language decline. The primary therapeutic outcome measure is the change in the Western Aphasia Battery Aphasia Quotient from pretreatment to post-treatment, with secondary outcome measures including change scores on the Boston Naming Test, the Communicative Effectiveness Index, and discourse measures of informational content and rate. Neurobiological measures include change in total volume of activation for each hemisphere and for regions of interest including the lateral premotor area (including the pars opercularis of the inferior frontal gyrus). tDCS in combination with SLT may be safe and may lead to improved outcomes, with important implications for the costs and delivery of rehabilitation services for individuals with aphasia. PUBLIC HEALTH RELEVANCE: Aphasia is a common symptom of stroke that has enormous impact on the individual's day-to-day functional activities and emotional well-being. Transcranial direct current stimulation (tDCS) in combination with speech and language therapy may lead to improved outcomes and have important implications for the costs and delivery of rehabilitation services for individuals with aphasia. Optimizing language recovery and enhancing the quality of life of individuals with aphasia may facilitate their entry back into the community and the work force, thereby decreasing the financial costs to society.