Overcoming Learned Non-Use in Chronic Aphasia: Behavioral, fMRI, and QoL Outcomes

描述（由申请人提供）：尽管最近有证据表明慢性失语症治疗诱导的神经可塑性，但关于治疗变量对语言恢复的影响、支持这种恢复的神经机制以及生活质量（QoL）可测量的相关改善的证据仍存在问题。拟议研究的长期目标是更好地了解治疗变量如何影响慢性失语症的恢复，包括支持改善命名的大脑/行为机制，以及这些改善如何影响生活质量。目前的目标是：第一，确定强化治疗是否对中度至重度表达性失语症患者有效，无论言语练习如何;第二，确定治疗诱导的命名改善的特征神经模式;第三，描述受影响家庭中语言能力改善与生活质量之间的关系。目前的研究提出了一个纵向病例系列的失语症康复方法，重点是一个变量，内隐与外显治疗，对语言，神经生理学和心理社会的变化，在慢性中重度患者的影响。这三个具体目标是：1）确定在命名方面，限制性诱导语言治疗（CILT）后的增益是否超过非限制性语言治疗（CILT）后观察到的增益，超过失语症的类型和严重程度，以及增益是否可以随着时间的推移而保持。中心假设是，参与者，即使是那些持续严重的非流利性失语症和共病的言语失用症，将受益于两个强化治疗计划，在那些随机分配到CILT显着的收益。训练和练习的单词（即，在12个月的随访测试中，在CILT和CRISPR之后的“过度学习”）将显示出更好的维持; 2）表征与改善的图片命名相关的fMRI激活模式。工作假设是，改善命名与备用网络的调制，根据病变的部位/程度而变化;和3）量化的程度，改善短期强化语言治疗后与生活质量指标的变化相关，如失语症的参与者和他们的显着的其他人。初步数据表明，改进的命名可以“启动”陷入学习不使用的语言系统，并刺激已知与QoL相关的因素的行为变化，例如，自信、社会关系和独立性。这项研究是创新的，首先是因为三管齐下（行为，神经影像学，生活质量）纵向病例系列的方法和它的潜力，以证明有意义的长期变化所造成的短期，强化治疗加上维护家庭治疗计划，第二，因为它的重点，在一定程度上，在一个更严重的影响人口比通常研究。这一贡献是重要的，因为推进我们真正的解剖学，功能和行为的限制和中风后语言恢复的潜力的知识可能会影响的看法，影响提供服务的慢性失语症患者。 公共卫生相关性：这项拟议的研究与公共卫生有关，因为中风的发病率越来越高，预期寿命更长，目前生活在美国的人患有慢性，持续性中风后语言障碍和心理社会后果，严重限制了他们参与与有意义生活相关的日常活动的能力。此外，拟议的研究是相关的NIH的使命的核心，追求有关人性和行为的基本知识的应用，以尽量减少与健康有关的残疾的负担。

DESCRIPTION (provided by applicant): Despite recent evidence demonstrating treatment-induced neuroplasticity in chronic aphasia, questions remain regarding the influence of treatment variables on language recovery, the neural mechanisms supporting such recovery, and evidence of measurable, correlated improvements in quality of life (QoL). The long-range goal of the proposed study is to better understand how treatment variables affect recovery in chronic aphasia, including the brain/behavior mechanisms supporting improved naming, and how such improvements impact QoL. The current objective is: first, to determine whether intensive treatment for remediation of word-finding deficits is effective for persons with moderate-to-severe expressive aphasia, regardless of speech practice; second, to identify signature neural patterns of treatment-induced improvements in naming; and third, to characterize the relationship between improved language ability and QoL within affected families. The current study proposes a longitudinal case series approach to aphasia rehabilitation, focusing on the effect of one variable, implicit vs. explicit treatment, on linguistic, neurophysiological, and psychosocial changes in chronic moderate-to-severe patients. The three specific aims are: 1) To determine whether gains in naming following constraint-induced language therapy (CILT) exceed those observed following unconstrained language therapy (ULT), over and above type and severity of aphasia, and whether the gains can be maintained over time. The central hypothesis is that participants, even those with persistent severe nonfluent aphasia and co-morbid apraxia of speech, will benefit from both intensive treatment programs, with significant gains in those randomly assigned to CILT. Words that are trained and practiced (i.e., "overlearned") following CILT and ULT will show better maintenance in 12-month follow-up testing; 2) To characterize patterns of fMRI activation that correlate with improved picture naming. The working hypothesize is that improved naming correlates with modulation of spared networks that vary according to site/extent of lesion; and 3) To quantify the degree to which improvements following short-term intensive language therapy correlate with changes in QoL measures as perceived by both participants with aphasia and their significant others. Preliminary data suggest that improved naming can "jumpstart" language systems caught in learned non-use and stimulate behavioral changes in factors known to correlate with QoL, e.g., confidence, social relationships, and independence. This research is innovative, first because of the three-pronged (behavioral, neuroimaging, QoL) longitudinal case series approach and its potential to demonstrate meaningful long-term changes resulting from short-term, intensive treatment plus a maintenance home therapy program, and second, because it focuses, in part, on a more severely affected population than is customarily studied. This contribution is significant because advancing our knowledge of the true anatomical, functional, and behavioral limits and potential for post-stroke language recovery could influence perceptions that affect delivery of services to chronically aphasic persons. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because of the growing incidence of stroke, longer life expectancies, and the high prevalence of people currently living in the U.S. with chronic, persistent post-stroke language impairments and psychosocial consequences that significantly limit their ability to participate in routine activities associated with a meaningful life. Moreover, the proposed research is relevant to the core of NIH's mission to pursue applications of fundamental knowledge regarding human nature and behaviors in order to minimize the burdens of health-related disability.