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

描述(申请人提供)：尽管最近的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，仍然存在疑问。这项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康复，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，确定强化治疗对中到重度表达失语症患者是否有效，无论他们的言语实践如何；第二，确定治疗导致命名改善的标志性神经模式；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。本研究提出了失语症康复的纵向病例系列方法，重点关注内隐与外显治疗对慢性中重度患者的语言、神经生理和心理社会改变的影响。研究的三个具体目标是：1)确定限制诱导语言治疗(CILT)后的命名收益是否超过非约束性语言治疗(ULT)后观察到的收益，以及失语症的类型和严重程度是否能够随着时间的推移保持这种收益。中心假设是，参与者，即使是那些患有持续性严重不流利失语和共病言语失用症的人，也将从这两个强化治疗计划中受益，其中随机分配到CILT的患者会有显著的进步。在CILT和ULT之后训练和练习的单词(即“过度学习”)将在12个月的后续测试中显示出更好的维持性；2)表征与改进的图片命名相关的fMRI激活模式。工作假设是，命名的改善与备用网络的调节相关，该网络因病变部位/程度的不同而不同；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伴侣感知的生活质量指标变化的程度。初步数据表明，改进后的命名可以“启动”语言系统，使其陷入习得的不使用状态，并在已知的与生活质量相关的因素中刺激行为变化，例如自信、社会关系和独立性。这项研究具有创新性，首先是因为三管齐下(行为、神经成像、QOL)的纵向病例系列方法，以及它有可能展示短期强化治疗加上维持性家庭治疗计划所产生的有意义的长期变化，其次是因为它在一定程度上关注的是比通常研究更严重的受影响人群。这一贡献意义重大，因为提高我们对中风后语言恢复的真正解剖、功能和行为限制和潜力的了解可能会影响人们对慢性失语症患者的服务交付的看法。

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.