Effects of tDCS on spoken and written production in Primary Progressive Aphasia

 描述(申请人提供)：原发性进行性失语症(PPA)是一种相对常见的临床神经退行性综合征，首先影响语言能力。PPA通常起病早(50-60岁)，对工作和家庭生活造成不利影响。口语和书面语产生缺陷是最早受到影响的语言技能，对其进程具有重要的预测和诊断价值。对于受影响的个人，没有可用的治疗方法。行为语言疗法以及命名和拼写干预尤其显示出温和但令人鼓舞的进展，然而，这并不适用于未经训练的项目，也不会随着时间的推移而持续下去。经颅直流电刺激(TDC)是一种相对较新的、安全、非侵入性、非疼痛的脑电刺激；已有研究表明，在语言治疗期间使用它可以改善健康对照组以及中风和痴呆患者的语言和认知能力。重复和连续的tDCs会话被认为在大脑中诱导一种影响突触连接的长期增强。只有一项发表的研究(由我们小组发表)支持tdcs结合拼写疗法对PPA患者有有益影响。在这个项目中，我们建议研究在口语和书面语产生联合治疗期间，随着时间的推移，tDCs对PPA参与者的行为和神经调节作用。在具体目标1中，我们将检验这样一种假设，即当阳极tdcs与口语和书面语产生疗法结合使用时，将比单独使用行为口语和书面语产生疗法更能改善PPA患者的表现。我们还假设，随着时间的推移，改善将持续下去，并推广到受刺激的大脑区域所辅助的其他语言和认知功能，并将对参与者的生活质量产生积极影响。在特殊目标2中，我们测试了这样一个假设，即在通过体积和扩散张量成像(DTI)测量灰质体积和白质束损失的情况下，通过静息状态fMRI测量的功能连接性的变化在tDCS结合口语和书面语产生干预后比仅在行为性口语和书面语产生干预后更大。研究结果可能有助于优化未来对患有PPA或其他神经退行性疾病的患者的干预，为尚未证实有效治疗的神经退行性综合征提供新的治疗选择。更好地了解tDCs引起的行为和功能连接的变化将有助于深入了解阻止神经退行性变的方法，这可能会改善PPA和其他痴呆患者的生活质量。

 DESCRIPTION (provided by applicant): Primary progressive aphasia (PPA) is a relatively common clinical neurodegenerative syndrome that first and foremost affects language abilities. PPA usually has an early onset (50-60 years of age), detrimentally affecting work and family life. Spoken and written word production deficits are the earliest affected language skills with significant prognostic and diagnostic value for its course. There is no available treatment for affected individuals. Behavioral language therapy and naming and spelling interventions in particular have shown modest but encouraging gains, which, however, do not generalize to untrained items and do not sustain over time. Transcranial Direct Current Stimulation (tDCS) is a relatively new, safe, non-invasive, non-painful electrical stimulation of the brain; it has been shown to improve language and cognitive abilities in healthy controls and individuals with stroke and dementia when administered during language therapy. Repetitive and consecutive sessions of tDCS are thought to induce a type of long-term potentiation in the brain that affects synaptic connectivity. There is only one published study (by our group) supporting that tDCS coupled with spelling therapy has beneficial effects in people with PPA. In this project we propose to investigate the behavioral and neuromodulatory effects of tDCS during a combination of spoken and written word production therapy in PPA participants over time. In Specific Aim 1, we will test the hypothesis that anodal tDCS, when administered in combination with spoken and written word production therapy, will improve performance of individuals with PPA more than behavioral spoken and written word production therapy alone. We also hypothesize that improvements will be sustained over time and generalize to other language and cognitive functions subserved by the stimulated brain areas and will positively affect the quality of life of participants. In Speciic Aim 2, we test the hypothesis that changes in functional connectivity as measured by resting-state fMRI are greater after tDCS coupled with spoken and written word production intervention than after behavioral spoken and written word production intervention alone while controlling for gray matter volume and white matter tract loss as measured by volumetric and diffusion tensor imaging (DTI). Study results may help optimize future interventions in individuals with PPA or other neurodegenerative disease by providing novel treatment alternatives in a neurodegenerative syndrome with no proven effective treatment. A better understanding of the behavioral as well as functional connectivity changes due to tDCS will offer insights into ways of impeding neurodegeneration that may improve quality of life for individuals with PPA and other dementias.