Optimizing Targeted Interventions for Aphasia

慢性失语症的语言治疗不是恢复性的， 失语症是毁灭性的关于可改变的大脑靶点的知识还没有被用来催化有意义的治疗结果。经颅直流电刺激（tDCS）允许系统研究 大脑目标参与的影响。tDCS研究旨在恢复左半球对语言处理的偏见。tDCS具有很强的临床转化潜力，但它向卒中输送的弥散电流 大脑和不受控制的皮质剂量限制了推断的精确度。虽然tDCS可以用来塑造大脑半球对语言的贡献，并调查目标参与，但迄今为止， 没有使用它来达到这个目的，阻碍了失语症治疗发展的纵向进展。失语症 和tDCS研究缺乏有意义的语言结果和治疗引起的大脑变化的数据。 目前迫切需要对能够将多余的大脑区域诱导成 适应性参与功能改进。如果不能满足这一需要， 失语症对减轻残疾负担的希望不大。长期目标是优化失语症恢复 用临床上可转化的基于大脑的方法。本项目的总体目标是确定如何 诱导功能性语言改善和适应性变化，以保留语言功能皮层。中心假设是，慢性失语症患者的功能性语言结果将得到加强， 治疗的重点是使左半球的语言处理偏差正常化。其基本原理是，确定涉及大脑靶点的行为和连续治疗将允许优化治疗参数，并促进开发新颖和个性化的方法，以超越现状， 精确的神经康复在强有力的初步数据的指导下，这一假设将通过追求两个具体目标来检验：1）证明有针对性的右半球调制的增强效果;以及2） 测量治疗后大脑活动的正常化。根据第一个目标，语言治疗将是 与活动或假HD-tDCS配对，以抑制右额下回（三角部），之后 将测量叙述和命名方面的进步，并对两组进行比较。在第二个目标下， 脑功能的EEG测量将被表征并与叙述和命名结果相关。这 贡献将是显著的，因为它预计将广泛应用于临床人群， 会从治疗诱导的适应性大脑重组中受益。我们对这个项目的主要创新是 将一种经过验证的行为治疗方法与有针对性的“高清”tDCS相结合， （HD-tDCS）来集中抑制并控制对右额叶的皮质剂量。这些贡献 对于美国超过240万患有失语症的成年人来说是很重要的。

Language treatments for chronic aphasia are not restorative, and the psychosocial and economic impacts of aphasia are devastating. Knowledge of modifiable brain targets has not been harnessed to catalyze meaningful treatment outcomes. Transcranial direct current stimulation (tDCS) allows systematic investigations of the effects of brain target engagement. tDCS investigations aim to restore a left hemisphere bias for language processing. tDCS has strong clinical translational potential, but the diffuse current flow it delivers to the stroke brain and uncontrolled cortical dosage limits inferential precision. Although tDCS could be used to shape hemispheric contributions to language and investigate target engagement, methodological approaches so far have not employed it for that purpose, preventing vertical progress in aphasia treatment development. Both aphasia and tDCS research are lacking data on meaningful language outcomes and treatment-induced brain changes. There is a critical need for rigorous investigations of treatments capable of coaxing spared brain areas into adaptive participation for functional improvements. Failure to meet this need means that millions of people with aphasia will have little hope for easing of disability burden. The long-term goal is to optimize aphasia recovery with clinically translatable brain-based approaches. The overall objective of this project is to determine how to induce functional language improvement and adaptive changes to spared eloquent language cortex. The central hypothesis is that functional language outcomes for people with chronic aphasia will be enhanced when treatment focuses on normalizing language processing bias to the left hemisphere. The rationale is that identifying behavioral and adjunctive treatments that engage brain targets will allow optimization of treatment parameters and facilitate the development of novel and personalized approaches to move beyond the status quo and towards precision neurorehabilitation. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: 1) Demonstrate the enhancing effect of targeted right hemisphere modulation; and 2) Measure normalization of brain activity following treatment. Under the first aim, language treatment will be paired with active or sham HD-tDCS to inhibit right inferior frontal right gyrus (pars triangularis), after which gains in narrative and naming will be measured and the two groups compared. Under the second aim, changes in EEG measures of brain function will be characterized and related to narrative and naming outcomes. This contribution will be significant because it is expected to have broad application to clinical populations who would benefit from treatment-induced adaptive brain reorganization. Our major innovation for this project is the pairing of a proven behavioral treatment that will recruit language networks with targeted “high-definition” tDCS (HD-tDCS) to focus inhibition and control cortical dosage to the frontal right hemisphere. These contributions will be important for the more than 2.4 million adults in the United States living with aphasia.