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有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可测量的、相关的生活质量（QoL）改善的证据等问题仍然存在。本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，以及这种改善如何影响生活质量。当前的目标是：首先，确定对中度至重度表达性失语症患者进行强化治疗是否有效，而不考虑言语练习；其次，识别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的提高与生活质量之间的关系。目前的研究提出了一种纵向病例系列方法来研究失语症康复，重点关注一个变量，内隐治疗与外显治疗，对慢性中重度失语症患者的语言、神经生理和社会心理变化的影响。研究的三个具体目的是：1)确定约束诱导语言治疗（CILT）后在命名方面的收益是否超过非约束语言治疗（ULT）后所观察到的收益，超过失语症的类型和严重程度，以及这种收益是否可以长期保持。研究的中心假设是，参与者，即使是那些患有持续性严重非流利性失语症和共病性语言失用症的患者，也将从两种强化治疗方案中受益，其中随机分配到CILT的患者获益显著。在CILT和ULT之后训练和练习的单词（即“过度学习”）在12个月的随访测试中表现出更好的维护；2)表征与改进的图片命名相关的fMRI激活模式。工作假设是，改进的命名与根据病变部位/程度而变化的备用网络调制有关；3)量化短期强化语言治疗后的改善与失语症参与者及其重要他人感知的生活质量测量变化的相关性程度。初步数据表明，改进的命名可以“快速启动”语言系统，并刺激与生活质量相关的因素的行为变化，例如信心、社会关系和独立性。这项研究是创新的，首先是因为它采用了三管齐下（行为、神经影像学、生活质量）的纵向病例系列方法，并有可能证明短期强化治疗加上维持家庭治疗计划导致的有意义的长期变化，其次是因为它部分地关注了受影响更严重的人群，而不是传统的研究。这一贡献意义重大，因为我们对真正的解剖、功能和行为限制以及中风后语言恢复的潜力的了解，可能会影响对慢性失语症患者提供服务的认知。

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.