Treating Intention in Aphasia: Neuroplastic Substrates

描述（由申请人提供）：我们开发了一种新的治疗方法，通过操纵意向底物来帮助“非流利”失语症患者产生语言。意图部分包括用一个复杂的左手动作开始找词试验。在一项初步研究中，与没有意图成分的类似处理相比，这种处理在命名准确性方面的变化率更快。然而，治疗引起语言产生功能从左额叶转移到右额叶的假设仅在少数患者（N = 5）中得到了验证，这些患者的侧化在治疗前是可变的，并且没有使用适当的严格控制程序来验证侧化的转移是由于意图成分。拟议的研究将在更大的“不流利”失语症患者样本和适当的对照组中解决假设的偏侧转移。在平行组设计中，13名患者将接受意向治疗，13名患者将接受与意向相同的对照治疗，只是没有意向成分。所有受试者将在治疗前后参与功能磁共振成像（fMRI）的单词查找扫描，以测量侧额侧化和sma前活动的变化。只有在治疗前扫描中显示左额叶有相当程度活动的患者才能参加。长期目标是确定意向治疗是否在侧额叶和前sma活动中产生假设的右移。有三个具体目标：(1)确定以复杂的左手运动重复开始单词生成是否会导致前sma右半球偏侧化和侧额叶活动增加，以及这些变化是否可归因于治疗的意图成分；(2)通过功能磁共振成像（fMRI）确定与右额叶活动相关的后外侧皮层的活动是否比对照组表现出更大的右半球偏侧性，以及(3)确定在意向治疗期间，与对照组相比，右侧运动/前运动皮层的血流动力学反应（HDRs）的开始是否与参与者言语反应的时间开始更密切相关。该研究有以下潜在的好处：首先，如果成功，该治疗可以为“非流利”失语症患者提供一种新的治疗工具，以提高语言功能并减少痛苦。其次，通过强调语言产生的大脑机制中产生理想变化的机制，并通过功能磁共振成像验证目标变化，该治疗可以在失语治疗的发展中产生范式转变。

DESCRIPTION (provided by applicant): A new treatment manipulating intention substrates for language production in "nonfluent" aphasia patients was developed. The intention component involves initiating word-finding trials with a complex left-hand movement. In a preliminary study, the rate of change in naming accuracy was faster for this treatment than for a similar treatment without the intention component. However, the assumption that the treatment evokes a shift of language production functions from the left to the right frontal lobe has been tested only in a small number of patients (N = 5) whose lateralization was variable before treatment, and appropriate stringent control procedures to verify that the shift in lateralization was due to the intention component were not used. The proposed study will address the hypothesized shift in lateralization in a larger sample of "nonfluent" aphasia patients and with an appropriate control group. In a parallel group design, 13 patients will receive the intention treatment and 13 patients will receive a control treatment that is identical to the intention except that the intention component is absent. All subjects will participate in functional magnetic resonance imaging (fMRI) scans of word-finding before and after treatment to measure changes in lateralization of lateral frontal and pre-SMA activity. Only patients with a substantial degree of left frontal activity on the pre-treatment scan will participate. The long-term objective is to determine if the intention treatment produces the hypothesized rightward shift in lateral frontal and pre-SMA activity. There are three specific aims: (1) to determine if repetitive initiation of word production with a complex left-hand movement leads to increased right- hemisphere lateralization of pre-SMA and lateral frontal activity and if these changes can be attributed to the intention component of treatment, (2) to determine whether activity in posterior perisylvian cortices that is entrained to right frontal activity shows a greater increase in right-hemisphere lateralization for the intention than for the control group from pre- to post-treatment fMRI, and (3) to determine whether onset of hemodynamic responses (HDRs) in right motor/premotor cortex becomes more closely associated with the temporal onset of participants' spoken responses across treatment for the intention vs the control treatment. The proposed study has the following potential benefits: First, if successful, the treatment can provide a new treatment vehicle for increasing language function and reducing suffering in patients with "nonfluent" aphasia. Second, the treatment can produce a paradigm shift in the development of aphasia treatment by emphasizing mechanisms for producing desirable changes in the brain mechanisms for language production and by verifying the target changes with fMRI.