Transcranial Direct Current Stimulation and Aphasia Language Therapy

描述（由申请人提供）：本项I期探索性研究评估了重复经颅直流电刺激（tDCS）联合强化语音语言治疗（TESS）的安全性和可行性，并收集了慢性非流利性失语症患者在不同极性条件下的疗效初步数据。已在动物模型中研究了通过直接对大脑皮质施加刺激来促进大脑可塑性，取得了令人鼓舞的结果，随后应用于中风后运动缺陷的康复。应用于中风后的语言问题才刚刚出现，但结果表明，皮层刺激作为失语症康复的辅助策略的潜在作用。在现有的方法中，tDCS具有最大的临床应用潜力，因为它的非侵入性应用，易于管理和相对低的成本。然而，当它在一段长时间内（例如，在几周的康复期间）每天应用时，关于安全性的数据不足。此外，对于失语症患者，在何处最好地施加刺激的问题以前没有得到解决，即，对受损的左半球或完整的右半球施加阳极或阴极刺激。因此，本研究的具体目的是评估1 mA tDCS（阳极、阴极或假刺激）与强化电刺激联合应用时的安全性，每周5天，持续6周，持续13分钟。此外，评估和比较与每种刺激模式相关的治疗效果和神经生物学变化。将12名重度或中重度非流利性失语症患者随机分为三组：左半球阳极tDCS;左半球阴极tDCS;或假刺激。刺激部位由观察、模仿、口头阅读和单词生成的功能磁共振成像任务确定，其中左前运动皮层在指示刺激部位的三个相交图中的一个中激活。治疗包括1 mA tDCS（或假刺激）13分钟，同时进行语音语言治疗（ESTA），然后再进行77分钟的ESTA，总计90分钟的ESTA。口语练习是通过电脑进行的，包括句子的口语阅读和会话练习。主要终点是安全性，通过不良事件的数量或认知或语言下降的证据来衡量。主要的治疗结果指标是治疗前到治疗后西方失语症成套测验失语商数的变化，次要的结果指标包括波士顿失语症测验的变化评分、沟通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（包括外侧运动前区（包括额下回的盖部））的总激活量变化。tDCS与TDCS联合使用可能是安全的，并可能导致改善的结果，对失语症患者的康复服务的成本和提供具有重要意义。公共卫生相关性：失语症是中风的常见症状，对个体的日常功能活动和情绪健康有巨大影响。经颅直流电刺激（tDCS）结合言语和语言治疗可能会导致改善的结果，并对失语症患者的康复服务的成本和提供具有重要意义。优化语言恢复和提高失语症患者的生活质量可能有助于他们重返社区和劳动力，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.